Diastolic Dysfunction Research Articles

Discrepancy in the Diagnosis of Heart Failure With Preserved Ejection Fraction Between Supine Versus Upright Exercise Hemodynamic Testing.

Invasive exercise right heart catheterization is a gold standard in diagnosing heart failure with preserved ejection fraction (HFpEF). Body positions during the test influence hemodynamics. However, the discrepancy in HFpEF diagnosis between exercise testing in supine versus upright position is unknown. We conducted a 2-center prospective study enrolling patients referred for exercise right heart catheterization for HFpEF. We performed a Supright protocol integrating submaximal supine bicycle ergometry (20 W) followed by maximal upright bicycle ergometry with a breath-by-breath oxygen analyzer. HFpEF hemodynamic criteria specific to testing positions were applied. Patients were considered to have concordant HFpEF if they met criteria in both positions or discordant HFpEF if they met criteria only in the supine position. Of 36 patients who met HFpEF criteria in supine position, 18 (50%) did not meet criteria in upright position (discordant HFpEF). Discordant HFpEF had less atrial fibrillation (0% versus 55%; P<0.001), lower left atrial volume (60±14 versus 77±21 mL; P=0.010), and lower H2FPEF score (2.1±1.3 versus 5.1±2.3; P<0.001). In supine position, pulmonary arterial wedge pressure was lower in discordant HFpEF at rest (15±4 versus 19±7 mm Hg; P=0.040). In upright position, pulmonary arterial wedge pressure was lower in discordant HFpEF both at rest (8±4 versus 14±6 mm Hg; P=0.002) and at peak exercise (14±4 versus 27±7 mm Hg; P<0.001). Pulmonary arterial wedge pressure/cardiac output slope was lower in discordant HFpEF (1.6±1.7 versus 3.6±2.9; P<0.001). Maximal workload (46±18 versus 49±24 W; P=0.59) or peak oxygen consumption (11.4±2.8 versus 12.9±3.4 mL/[kg·min]; P=0.15) was similar between groups. Half of patients who met HFpEF criteria in the supine position did not meet the criteria in the upright position. Patients with a discordant HFpEF phenotype had less structural and hemodynamic abnormalities compared with those with concordant HFpEF. A Supright exercise right heart catheterization approach is feasible and merits further investigation to determine the clinical implications of discordant exercise hemodynamic findings in supine and upright positions.

Invasive haemodynamic assessment in heart failure with preserved ejection fraction.

Despite the increasing prevalence and substantial burden of heart failure with preserved ejection fraction (HFpEF), which constitutes up to 50% of all heart failure cases, significant challenges persist in its diagnostic and therapeutic strategies. These difficulties arise primarily from the heterogeneous nature of the condition, the presence of various comorbidities and a wide range of phenotypic variations. Considering these challenges, current international guidelines endorse the utilization of invasive haemodynamic assessments, including resting and exercise haemodynamics, as the gold standard for enhancing diagnostic accuracy in cases where traditional diagnostic methods yield inconclusive results. These assessments are crucial not only for confirming the diagnosis but also for delineating the complex underlying pathophysiology, enabling the development of personalized treatment strategies, and facilitating the precise classification of HFpEF phenotypes. In this review, we summarize the haemodynamic changes observed in patients with HFpEF, comparing resting and exercise-induced parameters to those of normal subjects. Additionally, we discuss the current role of invasive haemodynamics in HFpEF assessment and highlight its utility beyond diagnosis, such as identifying HFpEF comorbidities, guiding phenotype-based personalized therapies and characterizing prognostication. Finally, we address the challenges associated with utilizing invasive haemodynamics and propose future directions, focusing on integrating these assessments into routine HFpEF care.

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

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

Effects of sex and obesity on immune checkpoint inhibition-related cardiac systolic dysfunction in aged mice.

Despite accumulating data on underlying mechanisms, the influence of sex and prevalent cardio-metabolic co-morbidities on the manifestation and severity of immune checkpoint inhibitor (ICI)-induced cardiotoxicity has not been well defined. To elucidate whether sex and prevalent cardio-metabolic co-morbidities affect ICI-induced cardiotoxicity, we randomized 17-month-old male and female mice to receive control diet (CON) or high-fat diet (HFD) + L-NAME-a well-established mouse model of cardio-metabolic co-morbidities-for 17weeks (n = 5-7), and evaluated markers of T-cell function in the spleen. As expected, HFD + L-NAME significantly increased body- and heart weight, and serum cholesterol levels, and caused no systolic dysfunction, however, led to diastolic dysfunction, cardiomyocyte hypertrophy, and increased fibrosis only in males compared to corresponding CON. Western blot analyses of splenic immune checkpoint protein levels showed differential expression depending on sex and prevalent cardio-metabolic co-morbidities, suggesting T-cell exhaustion in both sexes on HFD + L-NAME, but more pronounced in males. In a sub-study with a similar setup, we tested cardiotoxic manifestations of ICI by treating mice with anti-PD-1 monoclonal antibody (ICI) for the last 2weeks of diet administration (n = 5-7). After 2weeks of ICI treatment, cardiac systolic functions significantly decreased in CON, but not in HFD + L-NAME groups of both sexes compared to baseline (before ICI administration). In conclusion, in this exploratory study using aged mice, we describe for the first time that ICI-related systolic dysfunction is diminished in both sexes when obesity and hypercholesterolemia are present, possibly due to obesity-related T-cell exhaustion.

Pulmonary gas exchange in relation to exercise pulmonary hypertension in patients with heart failure with preserved ejection fraction.

Exercise pulmonary hypertension (ePH), defined as a mean pulmonary artery pressure (mPAP)/cardiac output (Qc) slope >3 WU during exercise, is common in patients with heart failure with preserved ejection fraction (HFpEF). However, the pulmonary gas exchange-related effects of an exaggerated ePH (EePH) response are not well-defined, especially in relation to dyspnea on exertion (DOE) and exercise intolerance. 48 HFpEF patients underwent invasive (pulmonary and radial artery catheters) constant-load (20W) and maximal incremental cycle testing. Hemodynamic measurements (mPAP and Qc), arterial blood and expired gases, and ratings of breathlessness (RPB, Borg 0-10) were obtained. The mPAP/Qc slope was calculated from rest-to-20W. Those with a mPAP/Qc slope >4.2 (median) were classified as HFpEF+EePH (n=24) and those with a mPAP/Qc slope <4.2 were classified as HFpEF (without EePH) (n=24). The A-aDO2, VD/VT (Bohr equation), and the VE/VCO2 slope (from rest-to-20W) were calculated. PaO2 was lower (p=0.03), and VD/VT was higher (p=0.03) at peak exercise in HFpEF+EePH compared with HFpEF. A-aDO2 was similar at peak exercise between groups (p=0.14); however, HFpEF+EePH achieved the peak A-aDO2 at a lower peak work rate (p<0.01). The VE/VCO2 slope was higher in HFpEF+EePH compared with HFpEF (p=0.01). RPB was ≥1-unit higher at 20W and VO2peak was lower (p<0.01) in HFpEF+EePH compared with HFpEF. These data suggest that EePH contributes to pulmonary gas exchange impairments during exercise by causing a V/Q mismatch that provokes both ventilatory inefficiency and hypoxemia, both of which seem to contribute to DOE and exercise intolerance in patients with HFpEF.

Prevalence of transthyretin cardiac amyloidosis in undifferentiated heart failure with preserved ejection fraction.

Transthyretin amyloid cardiomyopathy (ATTR-CM) is an increasinglyrecognized cause of heart failure with preserved ejection fraction (HFpEF), which may be diagnosed non-invasively using 99 mTc 3,3-diphosphono-1,2-propanodicarboxylic acid (DPD) scintigraphy-based diagnostic criteria. Our aim was to determine the prevalence of ATTR-CM in an undifferentiated HFpEF cohort with a DPD scintigraphy-based screening protocol. Patients with HFpEF [ejection fraction (EF) ≥50%] aged ≥60years and no prior evaluation for cardiac amyloidosis or known monoclonal gammopathy attending a regional cardiology network were screened with DPD scintigraphy. Patients with positive myocardial uptake (Perugini grade 2 or 3) were tested for a monoclonal protein and transthyretin gene variant. Eighty-six subjects were prospectively enrolled: 56% female, mean age 77±8years, 63% New York Heart Association (NYHA) Class III and median N-terminal pro-brain natriuretic peptide (NT-proBNP) 1766ng/L [inter-quartile range (IQR) 731-3703]. DPD scintigraphy was positive in seven patients (8%). Monoclonal gammopathy of undetermined significance was present in one out of seven patients, and no pathogenic TTR gene variant was identified. The prevalence of wild-type ATTR-CM was 8% of this cohort. Compared with the HFpEF DPD scintigraphy-negative cohort, DPD scintigraphy-positive patients were older (86±3 vs. 76±8years), more frequently male (16% vs. 2%, P=0.02), and had significantly greater left ventricular (LV) wall thickness (16 vs. 12mm; P=0.002) and higher high-sensitivity troponin levels at diagnosis [78ng/L (IQR 21-116) vs. 11ng/L (IQR 9-17); P<0.001]. In an undifferentiated HFpEF cohort, 8% were found to have wild-type ATTR-CM using a DPD scintigraphy-based screening protocol. Screening undifferentiated HFpEF patients is associated with a significant diagnostic yield, which can be further increased by targeting older males with increased LV wall thickness and elevated high-sensitivity troponin levels.

Improving the hemocompatibility of centrifugal mechanical circulatory support devices at low flow rates.

An innovative solution has been recently proposed for the treatment of heart failure with preserved ejection fraction (HFpEF), using a centrifugal mechanical circulatory support (MCS) device. We sought firstly to assess the hemocompatibility of the proposed device. HFpEF treatment requires the blood pump to operate at low blood flow rate (0.05-0.5 L/min). Given high blood trauma expected in these conditions, we sought secondly to investigate design improvements in order to reduce this risk. Computational fluid dynamics was used to analyze the blood fluid filled within the centrifugal pump and to estimate the blood trauma due to its operation. This assessment is based on the computation of integrated quantities such as the hemolysis index and the turbulent dissipation energy. The hemolysis index associated with the present device is comparable to the figures from HVAD. With the proposed pump, for instance, an index of 0.0036 is obtained at 1 L/min and 3000 rpm. Using thinner blades for the impeller allows a 12% reduction of the hemolysis index in average, while reducing its diameter leads to an index 2.8 folds lower at 0.5 L/min. The present investigation shows the promising hemocompatibility of our centrifugal pump. Concerns about very high hemolysis generated at low flow rates could be overcome by reducing the impeller diameter. Experimental validations are planned to support our findings.

Association of Histologic Findings With Long-Term Outcomes in Symptomatic Obstructive Hypertrophic Cardiomyopathy Patients Undergoing Surgical Myectomy.

In hypertrophic cardiomyopathy, histologic findings like myocyte hypertrophy and disarray, interstitial fibrosis (IF), and small intramural coronary artery dysplasia (SICAD) result in left ventricular hypertrophy, diastolic dysfunction, arrhythmogenicity, and microvascular ischemia. The authors sought to evaluate the association between histology and outcomes in obstructive hypertrophic cardiomyopathy (oHCM) patients undergoing surgical myectomy (SM). The study included 1,722 symptomatic oHCM patients (mean age: 56 ± 14 years; 948 [55%] men) who underwent SM at a tertiary center between 2005 and 2018. The SM specimen was analyzed for presence and severity of: 1) myocyte hypertrophy; 2) myocyte disarray; 3) IF; and 4) SICAD. Histologic findings were graded as 0-3 (none, mild, moderate, and severe) and a score from 0-12 was calculated. Primary endpoint was a composite of death, appropriate defibrillator discharge, or cardiac transplantation during follow-up. Moderate and severe histologic findings were distributed as follows: myocyte hypertrophy (1,341 [78%]); disarray (237 [14%]); IF (448 [26%]); and SICAD (258 [15%]). The mean total histologic score was 5.1 ± 1.4. At 5.1 ± 5.2 years, there were 352 (20%) primary events (317 [18%] deaths). On spline analysis, a total histology score of >5 was associated with primary events. On Kaplan-Meier analysis, patients with a histology score >5 had greater events vs those with a score≤5 (147/598 [25%] vs 205/1124 [18%]; log-rank P value=0.002). On multivariable Cox analysis, total histology score >5 (HR: 1.24 [95%CI: 1.03-1.54]; P = 0.03) was independently associated with higher primary events. In symptomatic oHCM patients undergoing SM, a higher histologic score was independently associated with long-term outcomes.

A randomized trial of early cardiotoxicity in breast cancer patients receiving postoperative IMRT with or without serial cardiac dose constraints.

Optimal cardiac dose constraints in breast cancer (BC) patients undergoing postoperative intensity-modulated radiation therapy (IMRT) are unclear, although as low as possible is recommended. This trial proposes serial cardiac dose constraint to optimize cardiac safety. Postoperative BC patients eligible for anthracycline/taxanes-based chemotherapy or HER2-targeted therapy were randomized to cardiac safety arm with prespecified mean heart dose (MHD) (≤6 Gy), V30 (≤20%), and V10 (≤50%) constraints, or to a control arm with in-house protocol (mainly MHD ≤8 Gy). The primary endpoint was cumulative incidence of newly onset cardiac events within 1-year post-RT. An exploratory analysis examined the relationship between whole heart dose metrics and those of substructures. Of 199 participants, 93 were in the cardiac safety and 106 in the control arm. The cardiac safety group showed lower MHD, V10, and V30. The 1-year cardiac event incidence was slightly lower in the cardiac safety group (19.4%) compared to controls (24.9%). The LVEF and diastolic dysfunction rates were 0% and 5.4% in the study arm, and 1.9% and 8.8% in the control arm, respectively. The LAD, LV, and RV received the highest doses for left-sided patients. For right-sided patients, RA, RCA, and RV were most irradiated. The MHD, V10, and Dmax of heart significantly correlated with all substructure doses in either laterality. Our study supports the early cardiac safety profile using IMRT in BC patients receiving cardiac-toxic systemic therapy, with serial cardiac dose constraints. Combined constraints on MHD and dose-volume parameters are representative of the cardiac substructure dose.

Triglyceride-glucose index is associated with heart failure with preserved ejection fraction in different metabolic states in patients with coronary heart disease

BackgroundThe triglyceride-glucose (TyG) index is a surrogate indicator of insulin resistance. Therefore, we aimed to determine the association between TyG index and heart failure (HF) with preserved ejection fraction (HFpEF) in patients with coronary heart disease (CHD) and to explore whether such associations would be modified by different metabolic states.MethodsAmong 107,301 CHD patients, 62,794 were included to analyze the relationship between the TyG index and HF. Among them, 8,606 patients who had undergone echocardiography were included to identify different types of HF, including HF with reduced ejection fraction (HFrEF), HF with intermediate-range ejection fraction (HFmrEF), and HFpEF. Among them, 1896 patients were diagnosed with HFpEF. Logistic regression was used to analyze the relationship between the TyG index and HFpEF in CHD patients. In addition, the association between TyG index and HFpEF according to sex, age, blood lipids, and blood pressure was assessed.ResultsA baseline analysis of CHD patients divided into four groups according to the tertile level of the TyG index showed significant differences in the related parameters between the groups. In the multi-adjusted models, the TyG index was significantly associated with the risk of HFpEF (odds ratio [OR]: 1.17; 95% confidence interval [CI]: 1.09–1.25). After adjustment for multivariates, TyG index levels for T2 (OR: 1.33; 95% CI: 1.16–1.52) and T3 (OR: 1.52; 95% CI: 1.32–1.74) were associated with increased OR in HFpEF. In addition, the TyG index of CHD patients was significantly associated with HFpEF in older adults aged &amp;gt; 60 years (OR: 1.20; 95% CI: 1.11–1.29), hypertension (OR: 1.27; 95% CI: 1.17–1.37), and dyslipidemia (OR: 1.15; 95% CI: 1.08–1.24). Moreover, the OR (OR: 1.23; 95% CI: 1.11–1.36) in women is higher than in men (OR: 1.17; 95% CI: 1.02–1.22, indicating a stronger association between TyG index and HFpEF in women.ConclusionsOur findings demonstrated a significant association between TyG index and HFpEF in CHD patients. Furthermore, TyG index was independently associated with HFpEF in hypertension, dyslipidemia, and older patients (aged &amp;gt; 60 years). In addition, the association between the TyG index and HFpEF in CHD patients differed according to sex.

Left ventricular diastolic dysfunction worsens prognosis in patients with heart failure due to dilated cardiomyopathy.

The prognostic significance of left ventricular (LV) diastolic dysfunction (LVDD) severity in patients with dilated cardiomyopathy (DCM) remains uncertain. This study aimed to evaluate the association of LVDD severity and elevated left atrial pressure (eLAP) with patient outcomes in stable, non-acutely decompensated patients with DCM. This single-centre, retrospective, observational study involved 740 DCM patients (either inpatients or outpatients) managed at our tertiary cardiac centre between 2010 and 2021. Due to incomplete data, 96 patients were excluded. LVDD and eLAP were assessed using echocardiography according to the 2016 guidelines of the European Association of Cardiovascular Imaging (EACVI). The primary outcomes were all-cause mortality and heart failure (HF)-related mortality. The final cohort comprised of 644 DCM patients [mean age: 52±12years, LV ejection fraction (LVEF): 26±10%]. Over a median follow-up period of 41 (18.5-66.7) months, 105 (16.3%) patients died: 8 (5.3%) patients in the normal left atrial pressure (nLAP) group and 97 (19.6%) patients in the eLAP group. eLAP was identified as an independent prognostic factor for both all-cause mortality [hazard ratio (HR) 2.0; 95% confidence interval (CI) 1.1-3.7; P=0.01] and HF-related mortality (HR 2.5; 95% CI 1.01-6.5; P=0.04), even after adjusting for LVEF and atrial fibrillation (AF) presence. Additionally, HF-related mortality rates were significantly higher in patients with moderate to severe LVDD compared with those with mild LVDD [5 (3.3%) vs. 67 (13.6%), P<0.05]. This study's findings highlight the importance of assessing the severity of LVDD in patients with DCM, which provides incremental prognostic information over LVEF.

Clinical and electrocardiographic predictors of left ventricular diastolic dysfunction in patients with idiopathic premature ventricular contractions

Objectives: Tachycardiomyopathy is a well-known phenomenon with reduction in left ventricular (LV) systolic function. In our study, we aimed to investigate the effects of idiopathic premature ventricular contractions (PVCs) on LV diastolic function in patients with idiopathic PVCs. Methods: We included 63 patients who are candidates to undergo radiofrequency ablation due to idiopathic PVCs (27 male, 36 female; mean age 47.9 ±16.6 years). Patients were classified into two groups according to the presence of LV diastolic dysfunction. The percentage of PVC burden was calculated by dividing the daily PVC burden by the total heart beat per day. Coupling interval ratio was calculated with the formula of Coupling interval ratio = (Coupling interval/sinus cycle length)x100. Results: Age, presence of q wave in D2-D3, daily PVC burden, percentage of PVC burden, left atrial volume index, intervenricular septum thickness, and mitral E/e’ ratio were significantly higher; male gender, peak E-wave velocity, lateral and septal annular e' velocity were significantly lower in patients with LV diastolic dysfunction. Daily PVC burden and percentage of PVC burden were positively correlated with mitral E/e’ ratio and negatively correlated with lateral annular e' velocity. The coupling interval ratio was positively correlated with mitral E/e’ ratio. Age, daily PVC burden, and percentage of PVC burden were independent predictors of increased mitral E/e’ ratio. The cutoff value of the percentage of PVC burden was 15.59% for prediction of LV diastolic dysfunction (sensitivity: 88.9%, specificity: 66.7%). Conclusions: Daily PVC burden, percentage of PVC burden, and coupling interval ratio are correlated with echocardiographic parameters of LV diastolic function.

Spleen tyrosine kinase: a novel pharmacological target for sepsis-induced cardiac dysfunction and multi-organ failure

Sepsis is a systemic condition caused by a dysregulated host response to infection and often associated with excessive release of proinflammatory cytokines resulting in multi-organ failure (MOF), including cardiac dysfunction. Despite a number of effective supportive treatments (e.g. ventilation, dialysis), there are no specific interventions that prevent or reduce MOF in patients with sepsis. To identify possible intervention targets, we re-analyzed the publicly accessible Gene Expression Omnibus accession GSE131761 dataset, which revealed an increased expression of spleen tyrosine kinase (SYK) in the whole blood of septic patients compared to healthy volunteers. This result suggests a potential involvement of SYK in the pathophysiology of sepsis. Thus, we investigated the effects of the highly selective SYK inhibitor PRT062607 (15mg/kg; i.p.) on sepsis-induced cardiac dysfunction and MOF in a clinically-relevant, murine model of sepsis. PRT062607 or vehicle (saline) was administered to 10-weeks-old C57BL/6 mice at 1h after the onset of sepsis induced by cecal ligation and puncture (CLP). Antibiotics (imipenem/cilastatin; 2mg/kg; s.c.) and analgesic (buprenorphine; 0.05mg/kg; i.p.) were administered at 6h and 18h post-CLP. After 24h, cardiac function was assessed in vivo by echocardiography and, after termination of the experiments, serum and cardiac samples were collected to evaluate the effects of SYK inhibition on the systemic release of inflammatory mediators and the degree of organ injury and dysfunction. Our results show that treatment of CLP-mice with PRT062607 significantly reduces systolic and diastolic cardiac dysfunction, renal dysfunction and liver injury compared to CLP-mice treated with vehicle. In addition, the sepsis-induced systemic inflammation (measured as an increase in inflammatory cytokines and chemokines in the serum) and the cardiac activation of NF-kB (IKK) and the NLRP3 inflammasome were significantly reduced in CLP-mice treated with PRT062607. These results demonstrate, for the first time, that SYK inhibition 1h after the onset of sepsis reduces the systemic inflammation, cardiac dysfunction and MOF, suggesting a potential role of the activation of SYK in the pathophysiology of sepsis. Novel therapeutic strategies that inhibit SYK activity may be of benefit in patients with diseases associated with local or systemic inflammation including sepsis.

Comorbidities and determinants of health on heart failure guideline-directed medical therapy adherence: All of us

BackgroundHeart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF) are challenging conditions to treat due to complex pathophysiology and associated comorbidities. However, recent trials have demonstrated improved outcomes with guideline-directed medical therapy (GDMT) for each subtype of heart failure. ObjectiveWe investigated the relationship of determinants of health and risk factors with GDMT use for HFrEF and HFpEF in a large, diverse US cohort. MethodsUsing the NIH-sponsored All of Us Program, we compared demographics, risk factors (e.g., hypertension, diabetes, smoking), and SDOH measures between HFrEF and HFpEF in US adults aged 18 years and older. We examined the proportions of HFrEF patients receiving fewer than four or all four GDMTs. HFpEF patients receiving two medications were compared with those receiving less than two recommended medications. Multiple logistic regression was used for data analysis. ResultOf 6049 HFrEF patients, 5838 (97 %) received fewer than four GDMTs, and 210 (3 %) received quadruple therapy. Of 3774 HFpEF patients, 162 (4 %) were on 2/3 GDMT, and only 38 (1 %) were on all three recommended medications. Patients with ASCVD and diabetes had higher odds of being on more than half of the recommended GDMT for both HFrEF and HFpEF. Additionally, females had higher odds of being on 2/3 GDMT for HFpEF (1.46 [1.08, 2.00]). Race, income, education, and health insurance types did not predict GDMT optimization. ConclusionHFrEF and HFpEF GDMT remain underutilized. Future efforts to address comorbidities and system-wide healthcare interventions may improve heart failure GDMT.

Effects of systemic ventricular assist in failing Fontan patients: a theoretical analysis using a computational model

Mechanical circulatory support is a potential treatment for failing Fontan patients. In this study, we performed a theoretical analysis using a computational model to clarify the effects of systemic ventricular assist device (VAD) in failing Fontan patients. Cardiac chambers and vascular systems were described using the time-varying elastance model and modified Windkessel model, respectively. A VAD was simulated as a nonlinear function. In systolic and diastolic ventricular dysfunction and atrioventricular valve regurgitation models, systemic VAD increased the cardiac index and decreased the central venous pressure (CVP). However, in the high pulmonary vascular resistance model, CVP became extremely high above 15 mmHg to maintain the cardiac index when the pulmonary vascular resistance index (PVRI) was above 5 Wood units m2. In Fontan patients with ventricular dysfunction or atrioventricular valve regurgitation, systemic VAD efficiently improves the hemodynamics. In Fontan patients with PVRI of > 5 Wood units m2, systemic VAD seems ineffective.

Contemporary epidemiology of hospitalised heart failure with reduced versus preserved ejection fraction in England: a retrospective, cohort study of whole-population electronic health records.

Heart failure is common, complex, and often associated with coexisting chronic medical conditions and a high mortality. We aimed to assess the epidemiology of people admitted to hospital with heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF), including the period covering the COVID-19 pandemic, which was previously not well characterised. In this retrospective, cohort study, we used whole-population electronic health records with 57 million individuals in England to identify patients hospitalised with heart failure as the primary diagnosis in any consultant episode of an in-patient admission to a National Health Service (NHS) hospital. We excluded individuals with less than 1 year of medical history records in primary or secondary care; admissions to NHS hospitals for which less than 10% of heart failure cases were linkable to the National Heart Failure Audit (NHFA); individuals younger than 18 years at the time of the heart failure hospitalisation; and patients who died in hospital during the index heart failure admission. For patients with new onset heart failure, we assessed incidence rates of 30-day and 1-year all-cause and cause-specific (cardiovascular, non-cardiovascular, and heart failure-related) emergency rehospitalisation and mortality after discharge, and dispensed guideline-recommended medical therapy (GRMT). Follow-up occurred from the index admission to the earliest occurrence of the event of interest, death, or end of data coverage. We estimated adjusted hazard ratios (HRs) to compare HFrEF with HFpEF. We computed population-attributable fractions to quantify the percentage of outcomes attributable to coexisting chronic medical conditions. Among 233 320 patients identified who survived the index heart failure admission across 335 NHS hospitals between Jan 1, 2019, and Dec 31, 2022, 101 320 (43·4%) had HFrEF, 71 910 (30·8%) had HFpEF, and 60 090 (25·8%) had an unknown classification. In patients with new onset heart failure, there were reductions in all-cause 30-day (-5·2% [95% CI -7·7 to -2·6] in 2019-22) and 1-year rehospitalisation rates (-3·9% [-6·6 to -1·2]). Declining 30-day rehospitalisation rates affected patients with HFpEF (-4·8% [-9·2 to -0·2]) and HFrEF (-6·2% [-10·5 to -1·6]), although 1-year rates were not statistically significant for patients with HFpEF (-2·2% [-6·6 to 2·3] vs -5·7% [-10·6 to -0·5] for HFrEF). There were no temporal trends in incidence rates of 30-day or 1-year mortality after discharge. The rates of all-cause (HR 1·20 [1·18-1·22]) and cause-specific rehospitalisation were uniformly higher in those with HFpEF than those with HFrEF. Patients with HFpEF also had higher rates of 1-year all-cause mortality after discharge (HR 1·07 [1·05-1·09]), driven by excess risk of non-cardiovascular death (HR 1·25 [1·21-1·29]). Rates of rehospitalisation and mortality were highest in patients with coexisting chronic kidney disease, chronic obstructive pulmonary disease, dementia, and liver disease. Chronic kidney disease contributed to 6·5% (5·6-7·4) of rehospitalisations within 1 year for HFrEF and 5·0% (4·1-5·9) of rehospitalisations for HFpEF, double that of any other coexisting condition. There was swift implementation of newer GRMT, but markedly lower dispensing of these medications in patients with coexisting chronic kidney disease. Rates of rehospitalisation in patients with heart failure in England have decreased during 2019-22. Further population health improvements could be reached through enhanced implementation of GRMT, particularly in patients with coexisting chronic kidney disease, who, despite being at high risk, remain undertreated. Wellcome Trust, Health Data Research UK, British Heart Foundation Data Science Centre.

Follow-Up Study of Percutaneous Intramyocardial Septal Radiofrequency Ablation in the Treatment of Hypertrophic Obstructive Cardiomyopathy With HFpEF.

The study aimed to evaluate the changes of left ventricular diastolic function and the improvement of clinical symptoms in hypertrophic cardiomyopathy (HCM) patients with heart failure with preserved ejection fraction (HFpEF) after percutaneous intramyocardial septal radiofrequency ablation (PIMSRA). This study enrolled 31 adult HCM patients with HFpEF who underwent PIMSRA treatment. Electrocardiogram, imaging, and blood biochemical examinations were performed on these patients during a 6-month follow-up. Compared with the baseline, at 6 months after PIMSRA, patients showed significant reductions in peak left ventricular outflow tract pressure gradients (resting gradient: from a mean of 83.24 to 23.40mmHg, p < 0.001; postexercise gradient: from a mean of 109.70 to 33.39mmHg, p< 0.001). The interventricular septal thickness reduced from a mean of 22.90 to 17.48mm, p < 0.001. The E/e' decreased from a median of 18.67 to 11.54, p < 0.001. The 6-minute walk distance (6MWD) increased from a mean of 359.03 to 435.81 m, p < 0.001. The Kansas City Cardiomyopathy Questionnaire Overall Summary Score (KCCQ OS) increased from a mean of 57.57 to 71.93, p < 0.001. The number of HFpEF patients diagnosed according to the European Society of Cardiology's Heart Failure Association HFA-PEFF score decreased from 31 to 23. None of the patients had new-onset bundle branch block or complete heart block after PIMSRA. PIMSRA is a safe and effective treatment. It can improve left ventricular diastolic function and quality of life in HCM patients.

Early Pathological Mechanisms in a Mouse Model of Heart Failure with Preserved Ejection Fraction.

Heart failure with preserved ejection fraction (HFpEF) constitutes more than half of all HF cases, yet evidence-based therapies remain lacking due to limited understanding of its underlying pathological mechanisms. Our study aimed to uncover early pathological mechanisms in HFpEF by exposing mice to dietary conditions resembling a Western diet-rich in fats, salt, and low in fiber-alongside excess mineralocorticoids to replicate significant aspects of human HFpEF. Echocardiography was performed at both 3-week and 6-week intervals post-challenge, revealing cardiac alterations as early as 3-weeks. While ejection fraction remained preserved, mice exhibited signs of diastolic dysfunction, reduced stroke volume, and left atrial enlargement. Additionally, changes in pulmonary flow velocities were noted by the 3-week mark, suggesting elevated pulmonary pressure. Extracardiac comorbidities included organ congestion, increased adiposity, impaired glucose tolerance, and hypercholesterolemia. Molecular analyses unveiled evidence of low-grade inflammation, oxidative stress, and impaired NO-cGMP-PKG signaling, contributing to the observed decrease in titin phosphorylation, thereby impacting myocardial stiffness. Additionally, impaired NO signaling might have influenced the alterations observed in coronary flow reserve. Moreover, dysregulation of calcium signaling in cardiomyocytes and reduced SR load were observed. Interestingly, elevated phosphorylation of cMyBP-C was linked to preserved ejection fraction despite reduced SR load. We also observed intestinal atrophy, possibly due to low dietary fiber intake and diminished gut perfusion, potentially contributing to systemic low-grade inflammation. These findings reveal how excess mineralocorticoids-salt-induced hypertension, and dietary factors, like high-fat and low-fiber intake, contribute to cardiac dysfunction and metabolic disturbances, offering insights into early HFpEF pathology in this model.

Causal Association Between Heart Failure and Sepsis: Insights from Mendelian Randomization and Observational Studies.

We aimed to identify the association between heart failure (HF) with sepsis and its mortality through Mendelian randomization (MR) and observational studies. In MR study, we utilized public summary statistics from genome-wide association studies (GWAS). We conducted univariable, multivariable and network MR analyses to investigate causal relationships between HF and sepsis, and mediating roles of cytokines and growth factors. We performed an observational analysis using the MIMIC-IV database. Propensity score matching (PSM) and logistic regression models were employed to explore causal relationships between HF and sepsis, besides short-, medium-, and long-term mortality associated with sepsis. In univariable MR analysis, there was a causal relationship between genetically predicted HF (OR = 1.15, 95% CI = 1.02-1.29, P = 0.025) and sepsis. In multivariable and network MR analyses, βNGF was independently associated with sepsis. And it mediated 17.6% (95% CI 2.45-30.72%) of HF effect on sepsis. In the real-world observational study, acute on chronic diastolic (congestive) heart failure (DCHF) (OR = 1.59, 95% CI = 1.31-1.93, P < 0.001), acute DCHF (OR = 2.52, 95% CI = 1.61-3.95, P = 0.010), and acute diastolic heart failure (DHF) (OR = 1.52, 95% CI = 1.06-2.19, P = 0.024) after PSM were associated with occurrence of sepsis. Chronic systolic (congestive) heart failure (SCHF) was associated with increased 28-day (OR = 1.75, 95% CI = 1.06-2.91, P = 0.030), 1-year (OR = 1.80, 95% CI = 1.08-3.00, P = 0.023), and 2-year (OR = 1.86, 95% CI = 1.12-3.10, P = 0.018) mortality in sepsis. Observational and MR analyses showed a causal relationship between HF and sepsis. Chronic SCHF was related to increased short/long-term mortality in sepsis. Our study indicated βNGF a key factor in HF-induced sepsis.

Epidemiological Profile and Correlates for Left Ventricular Diastolic Dysfunction among Patients Attending a Tertiary Health Facility in India

Background: There is an increasing recognition that congestive heart failure (CHF), caused by diastolic dysfunction (DD) (diastolic heart failure), is common and causes significant morbidity and mortality. Methods: The institution-based cross-sectional study was conducted among 119 subjects to determine the epidemiological profile, and regression analysis was used to evaluate the association of clinico-social correlates with the likelihood of developing DD. Result: The mean age of subjects was 51.6(±17.7) years. The mean systolic (SBP) and diastolic blood pressures (DBP) were 130(±18.9) mm Hg and 82.1(±11.1) mm Hg, respectively. Thirty-three (27.7%) subjects were hypertensive. Twelve (10%) were diabetic and experienced heart failure. DD was present in 54 (45.4%) subjects. Age, diabetes, ejection fraction (EF), and interventricular septal thickness in diastole (IVSd) were significant (P &lt; 0.05) correlates of DD. Mean values of age, body mass index (BMI), EF, IVSd, and left ventricular posterior wall thickness in diastole (LVPWD) were higher in subjects with DD. Hypertension contributed to 1.63 times greater odds of developing DD. Conclusion: The prevalence of DD increased with age among hypertensive and diabetic participants. Preventive strategies directed toward identifying subclinical signs of early stage and aggressive blood pressure and blood sugar control are likely to offer the greatest promise for reducing the incidence of DD.