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Introduction: Heart failure is one of the most common reasons for hospital admission in those aged 65 and over with consequent high costs for the healthcare system. Despite improvements in the treatment of patients with chronic HF with reduced EF, the survival of the patients hospitalized for HF remains poor, with one-year mortality of 30% and 5-year mortality up to 50%. Objective: To determine the prevalence of diastolic heart failure in patients with type 2 Diabetes mellitus in a tertiary care hospital. Methodology: This study was hospital based Cross-sectional observational study conducted in In-patient and outpatient department of Apollo Gleneagles Hospitals Kolkata involving 85 patients between 40-65 years of age both males and females from the general medical inpatient and outpatient pool of Apollo Gleneagles Hospitals Kolkata. Results: Prevalence of diastolic dysfunction was 63.5% among the patients with type-2 DM. Only 14.8% and 7.4% of the patients had Grade-III and Grade-IV DD respectively. Chi-square test showed that there was significant association between age and Diastolic Dysfunction of the patients (p<0.0001). Chi-square test showed that there was significant association between gender and DD of the patients (p=0.019). Chi-square test showed that there was significant association between obesity and DD of the patients (p=0.002). Conclusion: There was significant association between age and diastolic dysfunction of patients (p<0.0001). Obesity is a strong risk factor for heart failure. Chi-square test showed that there was significant association between obesity and DD of patients (p=0.002). There was significant association between level of HbA1c and DD of the patients. Prevalence of DD increases with value of HbA1c. [ABSTRACT FROM AUTHOR]

Despite the presence of various signs of cardiac amyloidosis ("red flags"), the introduction into routine practice of new non-invasive diagnostic methods (Speckle Tracking technology using echocardiography, myocardial scintigraphy with technetium pyrophosphate, genetic testing, screening for free light chains of immunoglobulins to exclude AL-amyloidosis), which have high specificity and sensitivity, transthyretinic (ATTR) cardiomyopathy is still a difficult to diagnose disease, especially in the early stages when treatment is most effective. The article presents a clinical case of ATTR-amyloidosis with predominant heart damage, manifested by severe diastolic heart failure resistant to treatment. The timing, from the moment of the first episode of decompensation of heart failure to death, is 4 months, which confirms the rapid progression of severe biventricular dysfunction of the heart. Despite the presence of cardiac and extracardial "red flags" of ATTR-amyloidosis in the patient, the diagnosis was established at autopsy. The paper analyzes possible errors of early diagnosis at the outpatient and inpatient stages of patient management.

Purpose of Review: To review the current evidence and modalities for treating pulmonary hypertension (PH) in heart failure with preserved ejection fraction (HFpEF). Recent Findings: In recent years, several therapies have been developed that improve morbidity in HFpEF, though these studies have not specifically studied patients with PF-HFpEF. Multiple trials of therapies specifically targeting the pulmonary vasculature such as phosphodiesterase (PDE) inhibitors, prostacyclin analogs, endothelin receptor antagonists (ERA), and soluble guanylate cyclase stimulators have also been conducted. However, these therapies demonstrated lack of consistency in improving hemodynamics or functional outcomes in PH-HFpEF. Summary: There is limited evidence to support the use of pulmonary vasculature-targeting therapies in PH-HFpEF. The mainstay of therapy remains the treatment of the underlying HFpEF condition. There is emerging evidence that newer HF therapies such as sodium-glucose transporter 2 inhibitors and angiotensin-receptor-neprilysin inhibitors are associated with improved hemodynamics and quality of life of patients with PH-HFpEF. There is also a growing realization that more robust phenotyping PH and right ventricular (RV) function may hold promise for therapeutic strategies for patients with PH-HFpEF. [ABSTRACT FROM AUTHOR]

The syndrome of heart failure (HF) with preserved ejection fraction (HFpEF) makes up about half of the HF population. The HF mechanisms in these patients are varied and not fully understood. In addition, the term "diastolic HF" was switched to HFpEF because of difficulties in measuring the left ventricular (LV) diastolic performance. In the late stages, HFpEF carries a prognosis that is as bad as or worse than that of HFrEF. Hence, it is important to recognize LV diastolic impairment at an earlier stage so that the causal mechanisms, if any, can be treated to retard its progression. Despite the availability of numerous disease-modifying agents for HFrEF, there are hardly any available treatments for HFpEF. With our aging population, there will be an epidemic of HFpEF and hence this entity needs attention and respect. In this paper, we review the fundamental mechanisms of HFpEF, the physiology of LV filling and how LV diastolic function can be comprehensively measured. We also speculate how this may help with the early recognition of diastolic HF and its treatment. [ABSTRACT FROM AUTHOR]

Introduction: Type 1 diabetes (T1D) is a metabolic disease characterized by insulin deficiency and subsequent hyperglycemia. Cardiovascular diseases are the prime cause of mortality and morbidity among patients with T1D. Accumulating metabolic disturbances and accelerated cardiac fibrosis fuel the development of heart dysfunction. As insulin resistance (IR) is a risk factor for the development and worsened course of heart failure, this study aimed to assess its impact on heart function in patients with T1D. Methods: Adult participants were recruited prospectively. The inclusion criteria included a diagnosis of T1D. The exclusion criteria were other types of diabetes, symptoms/treatment of heart failure, AST and/or ALT exceeding the upper reference limit by ≥2x, hepatitis, alcoholism, metformin treatment, and pregnancy. The participants underwent a medical interview, physical examination, biochemical test, and echocardiography. Results: The mean age in the study group was 38 ± 9.6 years, and the mean diabetes duration was 21.8 ± 11.3 years. The median BMI in the study cohort was 23.39 kg/m2. Patients with IR had significantly lower mitral E/A ratio and left ventricular and left atrial volume ratio (LVLAVR), higher LV mass index, and presented with altered mitral annular velocities. Conclusions: IR seems to accelerate the pattern of typical changes in heart function among patients with T1D, especially in the overweight subgroup. [ABSTRACT FROM AUTHOR]

Background Half of patients with heart failure with preserved ejection fraction (HFpEF) remain undiagnosed by resting evaluation alone. Therefore, exercise testing is proposed. The diastolic stress test (DST), however, has limited sensitivity. We aimed to determine the clinical significance of adding the mean pulmonary artery pressure over cardiac output (mPAP/CO) slope to the DST in suspected HFpEF. Methods and Results In this prospective cohort study, consecutive patients (n=1936) with suspected HFpEF underwent exercise echocardiography with simultaneous respiratory gas analysis. These patients were stratified by exercise E over e′ (exE/e′) and mPAP/CO slope, and peak oxygen uptake, natriuretic peptides (NT‐proBNP [N‐terminal pro‐B‐type natriuretic peptide]), and score‐based HFpEF likelihood were compared. Twenty‐two percent of patients (n=428) had exE/e′3 mm Hg/L per min, 24% (n=464) had a positive DST (exE/e′≥15), and 54% (n=1044) had a normal DST and slope. Percentage of predicted oxygen uptake was similar in the group with exE/e′3 mm Hg/L per min despite a negative DST. These patients had HFpEF characteristics and a peak oxygen uptake as low as patients with a positive DST. Therefore, an elevated mPAP/CO slope might indicate HFpEF irrespective of the DST result.

Aims To study the impact of heart failure with preserved ejection fraction (HFpEF) vs. aortic stenosis (AS) lesion severity on left ventricular (LV) hypertrophy, diastolic dysfunction, left atrial (LA) dysfunction, haemodynamics, and exercise capacity. Methods and results Patients (n = 206) with at least moderate AS (aortic valve area ≤0.85 cm/m2) and discordant symptoms underwent cardiopulmonary exercise testing with simultaneous echocardiography. The population was stratified according to the probability of underlying HFpEF by the heavy, hypertension, atrial fibrillation, pulmonary hypertension, elder, filling pressure (H2FPEF) score [0–5 (AS/HFpEF−) vs. 6–9 points (AS/HFpEF+)] and AS severity (Moderate vs. Severe). Mean age was 73 ± 10 years with 40% women. Twenty-eight patients had Severe AS/HFpEF+ (14%), 111 Severe AS/HFpEF− (54%), 13 Moderate AS/HFpEF+ (6%), and 54 Moderate AS/HFpEF− (26%). AS/HFpEF+ vs. AS/HFpEF− patients, irrespective of AS severity, had a lower LV global longitudinal strain, impaired diastolic function, reduced LV compliance, and more pronounced LA dysfunction. The pulmonary arterial pressure–cardiac output slope was significantly higher in AS/HFpEF+ vs. AS/HFpEF− (5.4 ± 3.1 vs. 3.9 ± 2.2 mmHg/L/min, respectively; P = 0.003), mainly driven by impaired cardiac output and chronotropic reserve, with signs of right ventricular pulmonary arterial uncoupling. AS/HFpEF+ vs. AS/HFpEF− was associated with a lower peak aerobic capacity (11.5 ± 3.7 vs. 15.9 ± 5.9 mL/min/kg, respectively; P < 0.0001) but did not differ between Moderate and Severe AS (14.7 ± 5.5 vs. 15.2 ± 5.9 mL/min/kg, respectively; P = 0.6). Conclusion A high H2FPEF score is associated with a reduced exercise capacity and adverse haemodynamics in patients with moderate to severe AS. Both exercise performance and haemodynamics correspond better with intrinsic cardiac dysfunction than AS severity. [ABSTRACT FROM AUTHOR]

Background Constrictive pericarditis is a rare complication of pericarditis and is difficult to diagnose due to non-specific presentation. It mostly presents with right-sided heart failure as a consequence of a rigid pericardium that encases the heart causing impaired diastolic filling. Case summary We present the case of a patient with signs and symptoms of dyspnoea and right-sided heart failure who was initially diagnosed with heart failure with preserved ejection fraction (HFpEF) but remained symptomatic despite being euvolaemic after treatment. A septal bounce and shudder on echocardiogram prompted further investigation. Eventually, cardiac magnetic resonance (CMR) imaging and invasive biventricular pressure measurements led to the diagnosis of constrictive pericarditis. A pericardiectomy was performed after which the patient was relieved of symptoms. Discussion Constrictive pericarditis can mimic HFpEF. Due to its potentially curable character, timely recognition is of cardinal importance. In patients with symptoms of severe right-sided heart failure not resolving after diuretic therapy, a septal shudder on echocardiography should trigger further investigation, with e.g. CMR and cardiac catheterization. [ABSTRACT FROM AUTHOR]

IntroductionType 1 diabetes (T1D) is a metabolic disease characterized by insulin deficiency and subsequent hyperglycemia. Cardiovascular diseases are the prime cause of mortality and morbidity among patients with T1D. Accumulating metabolic disturbances and accelerated cardiac fibrosis fuel the development of heart dysfunction. As insulin resistance (IR) is a risk factor for the development and worsened course of heart failure, this study aimed to assess its impact on heart function in patients with T1D.MethodsAdult participants were recruited prospectively. The inclusion criteria included a diagnosis of T1D. The exclusion criteria were other types of diabetes, symptoms/treatment of heart failure, AST and/or ALT exceeding the upper reference limit by ≥2x, hepatitis, alcoholism, metformin treatment, and pregnancy. The participants underwent a medical interview, physical examination, biochemical test, and echocardiography.ResultsThe mean age in the study group was 38 ± 9.6 years, and the mean diabetes duration was 21.8 ± 11.3 years. The median BMI in the study cohort was 23.39 kg/m2. Patients with IR had significantly lower mitral E/A ratio and left ventricular and left atrial volume ratio (LVLAVR), higher LV mass index, and presented with altered mitral annular velocities.ConclusionsIR seems to accelerate the pattern of typical changes in heart function among patients with T1D, especially in the overweight subgroup.

Abstract Aims Diagnosis of heart failure with preserved ejection fraction (HFpEF) can be challenging. This study aimed to evaluate the potential of a webtool to enhance the scoring accuracy when applying the complex HFA‐PEFF and H2FPEF algorithms, which are commonly used for diagnosing HFpEF. Methods and results We developed an online tool, the HFpEF calculator, that enables the automatic calculation of current HFpEF algorithms. We assessed the accuracy of manual vs. automatic scoring, defined as the percentage of correct scores, in a cohort of cardiologists with varying clinical experience. Cardiologists scored eight online clinical cases using a triple cross‐over design (i.e. two manual–two automatic–two manual–two automatic). Data were analysed in study completers (n = 55, 29% heart failure specialists, 42% general cardiologists, and 29% cardiology residents). Manually calculated scores were correct in 50% (HFA‐PEFF: 50% [50–75]; H2FPEF: 50% [38–50]). Correct scoring improved to 100% using the HFpEF calculator (HFA‐PEFF: 100% [88–100], P

Introduction: Pericardial effusion is an indicator of poor prognosis in patients with cancer. We investigated the effect of pericardial effusion development on right ventricular function in oncology patients receiving chemotherapy for malignancy. Methods: A total of 90 patients who were followed up in the oncology clinic and who applied to our outpatient clinic for routine cardiac examination were included in the study. Echocardiography was performed on the patients, and they were divided into two groups: patients with and without pericardial effusion. Demographic characteristics and, clinical and laboratory findings of the patients were recorded. The right ventricular functions of the patients were then evaluated. Results: Pericardial effusion was in 30 (33.3%) of 90 patients included in the study. The mean age of patients without pericardial effusion was 57.33±15.59, and the mean age of patients with effusion was 60.27±13.51, and it was similar between the groups (p=0.36). No statistically significant difference was detected between the groups in right ventricular (RV) fractionated area change, RV-early peak, tricuspid annular plane systolic excursion, pulmonary artery pressure, E/E', and heart failure with preserved ejection fraction values, which are parameters that indicate right ventricular functions and diastolic dysfunction. However, RV systolic velocity and RV-AM, which are indicators of diastolic dysfunction, were found at higher rates in the patient group with pericardial effusion (p-value 0.041 and 0.001, respectively). In addition, Mitral E velocity was found to be lower in the patient group with pericardial effusion (p=0.032). Conclusion: In malignancy patients who develop pericardial effusion, we recommend that diastolic parameters be checked and close clinical follow-up of the patients be performed before overt heart failure clinic develops. It should be kept in mind that the development of pericardial effusion in oncology patients receiving chemotherapy does not mean right ventricular failure.

Background: Heart failure is described by a lack of confirmed efficient therapies and exercise intolerance. Engagement in physical activity decreases the possibility of adverse cardiovascular consequences involving heart failure. The Purpose of the Study: Determine the effect of different types of aerobic training on peak VO2 and ejection fraction in diastolic heart failure patients. Subject and Methods: The study was designed as a randomized control trail. Forty‐eight eligible male patients with diastolic heart failure, aged between 50 and 65 years old, enrolled in this study. They were picked up from Police hospital outpatient clinic and were assigned to 2 equal groups in numbers. The first group (A) received aerobic exercise for the upper limb in the form of arm ergometer exercises, while the second group (B) received aerobic exercise for the lower limb in the form of cycling. Training duration for both groups was 3 sessions/week for 12 weeks. Peak VO2, and ejection fraction of both groups were measured and compared pre‐ and post‐treatment. Results: There was no significant difference (p > 0.05) in the ejection fraction between groups post‐treatment. However, a significant increase (p < 0.001) was observed in the peak VO2 of group B when compared to group A post‐treatment. Conclusion: There is no effect of different types of aerobic training on ejection fraction in diastolic heart failure patients, but lower limb exercise is more effective than upper limb exercise in improving peak VO2 in diastolic heart failure patients. Therefore, the current study recommended the use of lower limb exercise over upper limb exercise in training diastolic heart failure patients. Clinical Trial Registration: The study was registered in ClinicalTrial.gov as a clinical trial ID (NCT05637125). [ABSTRACT FROM AUTHOR]

Aims: Diagnosis of heart failure with preserved ejection fraction (HFpEF) can be challenging. This study aimed to evaluate the potential of a webtool to enhance the scoring accuracy when applying the complex HFA‐PEFF and H2FPEF algorithms, which are commonly used for diagnosing HFpEF. Methods and results: We developed an online tool, the HFpEF calculator, that enables the automatic calculation of current HFpEF algorithms. We assessed the accuracy of manual vs. automatic scoring, defined as the percentage of correct scores, in a cohort of cardiologists with varying clinical experience. Cardiologists scored eight online clinical cases using a triple cross‐over design (i.e. two manual–two automatic–two manual–two automatic). Data were analysed in study completers (n = 55, 29% heart failure specialists, 42% general cardiologists, and 29% cardiology residents). Manually calculated scores were correct in 50% (HFA‐PEFF: 50% [50–75]; H2FPEF: 50% [38–50]). Correct scoring improved to 100% using the HFpEF calculator (HFA‐PEFF: 100% [88–100], P < 0.001; H2FPEF: 100% [75–100], P < 0.001). Time spent on clinical cases was similar between scoring methods (±4 min). When corrections for faulty algorithm scores were displayed, cardiologists changed their diagnostic decision in up to 67% of cases. At least 67% of cardiologists preferred using the online tool for future cases in clinical practice. Conclusions: Manual calculation of HFpEF diagnostic algorithms is often inaccurate. Using an automated webtool to calculate HFpEF algorithms significantly improved correct scoring. This new approach may impact the eventual diagnostic decision in up to two‐thirds of cases, supporting its routine use in clinical practice. [ABSTRACT FROM AUTHOR]

Titin‐dependent stiffening of cardiomyocytes is a significant contributor to left ventricular (LV) diastolic dysfunction in heart failure with preserved LV ejection fraction (HFpEF). Small heat shock proteins (HSPs), such as HSPB5 and HSPB1, protect titin and administration of HSPB5 in vitro lowers cardiomyocyte stiffness in pressure‐overload hypertrophy. In humans, oral treatment with geranylgeranylacetone (GGA) increases myocardial HSP expression, but the functional implications are unknown. Our objective was to investigate whether oral GGA treatment lowers cardiomyocyte stiffness and attenuates LV diastolic dysfunction in a rat model of the cardiometabolic syndrome. Twenty‐one‐week‐old male lean (n = 10) and obese (n = 20) ZSF1 rats were studied, and obese rats were randomized to receive GGA (200 mg/kg/day) or vehicle by oral gavage for 4 weeks. Echocardiography and cardiac catheterization were performed before sacrifice at 25 weeks of age. Titin‐based stiffness (Fpassive) was determined by force measurements in relaxing solution with 100 nM [Ca2+] in permeabilized cardiomyocytes at sarcomere lengths (SL) ranging from 1.8 to 2.4 μm. In obese ZSF1 rats, GGA reduced isovolumic relaxation time of the LV without affecting blood pressure, EF or LV weight. In cardiomyocytes, GGA increased myofilament‐bound HSPB5 and HSPB1 expression. Vehicle‐treated obese rats exhibited higher cardiomyocyte stiffness at all SLs compared to lean rats, while GGA reduced stiffness at SL 2.0 μm. In obese ZSF1 rats, oral GGA treatment improves cardiomyocyte stiffness by increasing myofilament‐bound HSPB1 and HSPB5. GGA could represent a potential novel therapy for the early stage of diastolic dysfunction in the cardiometabolic syndrome. [ABSTRACT FROM AUTHOR]

Introduction: Pericardial effusion is an indicator of poor prognosis in patients with cancer. We investigated the effect of pericardial effusion development on right ventricular function in oncology patients receiving chemotherapy for malignancy. Methods: A total of 90 patients who were followed up in the oncology clinic and who applied to our outpatient clinic for routine cardiac examination were included in the study. Echocardiography was performed on the patients, and they were divided into two groups: patients with and without pericardial effusion. Demographic characteristics and, clinical and laboratory findings of the patients were recorded. The right ventricular functions of the patients were then evaluated. Results: Pericardial effusion was in 30 (33.3%) of 90 patients included in the study. The mean age of patients without pericardial effusion was 57.33±15.59, and the mean age of patients with effusion was 60.27±13.51, and it was similar between the groups (p=0.36). No statistically significant difference was detected between the groups in right ventricular (RV) fractionated area change, RV-early peak, tricuspid annular plane systolic excursion, pulmonary artery pressure, E/E', and heart failure with preserved ejection fraction values, which are parameters that indicate right ventricular functions and diastolic dysfunction. However, RV systolic velocity and RV-AM, which are indicators of diastolic dysfunction, were found at higher rates in the patient group with pericardial effusion (p-value 0.041 and 0.001, respectively). In addition, Mitral E velocity was found to be lower in the patient group with pericardial effusion (p=0.032). Conclusion: In malignancy patients who develop pericardial effusion, we recommend that diastolic parameters be checked and close clinical follow-up of the patients be performed before overt heart failure clinic develops. It should be kept in mind that the development of pericardial effusion in oncology patients receiving chemotherapy does not mean right ventricular failure. [ABSTRACT FROM AUTHOR]

Background COVID-19 infection and the COVID-19 vaccines have been associated with rare cases of pericarditis. We present a case of constrictive pericarditis (CP) following the vaccine. Case summary A 19-year-old healthy male started having progressive abdominal pain, emesis, dyspnoea, and pleuritic chest pain 2 weeks after the second dose of Pfizer vaccine. Computed tomography angiography chest revealed bilateral pleural effusions and pericardial thickening with effusion. Cardiac catheterization showed ventricular interdependence. Cardiac magnetic resonance (CMR) showed septal bounce and left ventricular tethering suggestive of CP. A total pericardiectomy was performed with significant symptom improvement. Pathology showed chronic fibrosis without amyloid, iron deposits, or opportunistic infections. Patient had Epstein–Barr Virus (EBV) viraemia 825 IU/mL and histoplasmosis complement-fixation positive with negative serum and urine antigen. Hypercoagulable panel and infectious workup were otherwise negative. The patient had resolution of cardiac symptoms at 3 months of follow-up. Discussion The patient developed progressive symptoms within 2 weeks of his second Pfizer vaccine. Echocardiogram and CMR had classic signs of CP, and pericardial pathology confirmed fibrotic pericardium. The patient had no prior surgery, thoracic radiation, or bacterial infection. Epstein–Barr Virus viraemia was thought to be reactionary, and histoplasmosis complement likely represented chronic exposure. The timing of symptoms and negative multidisciplinary workup raises the suspicion for COVID vaccine–induced CP. The COVID vaccines benefits far exceed the risks, but complications still can occur. Practitioners should have a high index of suspicion to allow prompt diagnosis of CP. [ABSTRACT FROM AUTHOR]

Abstract Aims Impaired myocardial energy homeostasis plays an import role in the pathophysiology of heart failure with preserved ejection fraction (HFpEF). Left ventricular relaxation has a high energy demand, and left ventricular diastolic dysfunction has been related to impaired energy homeostasis. This study investigated whether trimetazidine, a fatty acid oxidation inhibitor, could improve myocardial energy homeostasis and consequently improve exercise haemodynamics in patients with HFpEF. Methods and results The DoPING‐HFpEF trial was a phase II single‐centre, double‐blind, placebo‐controlled, randomized cross‐over trial. Patients were randomized to trimetazidine treatment or placebo for 3 months and switched after a 2‐week wash‐out period. The primary endpoint was change in pulmonary capillary wedge pressure, measured with right heart catheterization at multiple stages of bicycling exercise. Secondary endpoint was change in myocardial phosphocreatine/adenosine triphosphate, an index of the myocardial energy status, measured with phosphorus‐31 magnetic resonance spectroscopy. The study included 25 patients (10/15 males/females; mean (standard deviation) age, 66 (10) years; body mass index, 29.8 (4.5) kg/m2); with the diagnosis of HFpEF confirmed with (exercise) right heart catheterization either before or during the trial. There was no effect of trimetazidine on the primary outcome pulmonary capillary wedge pressure at multiple levels of exercise (mean change 0 [95% confidence interval, 95% CI −2, 2] mmHg over multiple levels of exercise, P = 0.60). Myocardial phosphocreatine/adenosine triphosphate in the trimetazidine arm was similar to placebo (1.08 [0.76, 1.76] vs. 1.30 [0.95, 1.86], P = 0.08). There was no change by trimetazidine compared with placebo in the exploratory parameters: 6‐min walking distance (mean change of −6 [95% CI −18, 7] m vs. −5 [95% CI −22, 22] m, respectively, P = 0.93), N‐terminal pro‐B‐type natriuretic peptide (5 (−156, 166) ng/L vs. −13 (−172, 147) ng/L, P = 0.70), overall quality‐of‐life (KCCQ and EQ‐5D‐5L, P = 0.78 and P = 0.51, respectively), parameters for diastolic function measured with echocardiography and cardiac magnetic resonance, or metabolic parameters. Conclusions Trimetazidine did not improve myocardial energy homeostasis and did not improve exercise haemodynamics in patients with HFpEF.

Abstract Aims Heart failure (HF) with preserved ejection fraction (HFpEF) is associated with cardiovascular (CV) and non‐CV events, but long‐term risk is poorly studied. We assessed incidence and predictors of the long‐term CV and non‐CV events. Methods and results Patients presenting with acute HF, EF ≥ 45%, and N‐terminal pro‐brain natriuretic peptide > 300 ng/L were enrolled in the Karolinska‐Rennes study in 2007–11 and were reassessed after 4–8 weeks in a stable state. Long‐term follow‐up was conducted in 2018. The Fine–Gray sub‐distribution hazard regression was used to detect predictors of CV and non‐CV deaths, investigated separately from baseline acute presentation (demographic data only) and from the 4–8 week outpatient visit (including echocardiographic data). Of 539 patients enrolled [median age 78 (interquartile range: 72–84) years; 52% female], 397 patients were available for the long‐term follow‐up. Over a median follow‐up time from acute presentation of 5.4 (2.1–7.9) years, 269 (68%) patients died, 128 (47%) from CV and 120 (45%) from non‐CV causes. Incidence rates per 1000 patient‐years were 62 [95% confidence interval (CI) 52–74] for CV and 58 (95% CI 48–69) for non‐CV death. Higher age and coronary artery disease (CAD) were independent predictors of CV death, and anaemia, stroke, kidney disease, and lower body mass index (BMI) and sodium concentrations of non‐CV death. From the stable 4–8 week visit, anaemia, CAD, and tricuspid regurgitation (>3.1 m/s) were independent predictors of CV death, and higher age of non‐CV death. Conclusions In patients with acute decompensated HFpEF, over 5 years of follow‐up, nearly two‐thirds of patients died, half from CV and the other half from non‐CV causes. CAD and tricuspid regurgitation were associated with CV death. Stroke, kidney disease, lower BMI, and lower sodium were associated with non‐CV death. Anaemia and higher age were associated with both outcomes. [Correction added on 24 March 2023, after first online publication: In the first sentence of the Conclusions, ‘two‐thirds’ has been inserted before ‘of patients died...’ in this version.]

Abstract Titin‐dependent stiffening of cardiomyocytes is a significant contributor to left ventricular (LV) diastolic dysfunction in heart failure with preserved LV ejection fraction (HFpEF). Small heat shock proteins (HSPs), such as HSPB5 and HSPB1, protect titin and administration of HSPB5 in vitro lowers cardiomyocyte stiffness in pressure‐overload hypertrophy. In humans, oral treatment with geranylgeranylacetone (GGA) increases myocardial HSP expression, but the functional implications are unknown. Our objective was to investigate whether oral GGA treatment lowers cardiomyocyte stiffness and attenuates LV diastolic dysfunction in a rat model of the cardiometabolic syndrome. Twenty‐one‐week‐old male lean (n = 10) and obese (n = 20) ZSF1 rats were studied, and obese rats were randomized to receive GGA (200 mg/kg/day) or vehicle by oral gavage for 4 weeks. Echocardiography and cardiac catheterization were performed before sacrifice at 25 weeks of age. Titin‐based stiffness (Fpassive) was determined by force measurements in relaxing solution with 100 nM [Ca2+] in permeabilized cardiomyocytes at sarcomere lengths (SL) ranging from 1.8 to 2.4 μm. In obese ZSF1 rats, GGA reduced isovolumic relaxation time of the LV without affecting blood pressure, EF or LV weight. In cardiomyocytes, GGA increased myofilament‐bound HSPB5 and HSPB1 expression. Vehicle‐treated obese rats exhibited higher cardiomyocyte stiffness at all SLs compared to lean rats, while GGA reduced stiffness at SL 2.0 μm. In obese ZSF1 rats, oral GGA treatment improves cardiomyocyte stiffness by increasing myofilament‐bound HSPB1 and HSPB5. GGA could represent a potential novel therapy for the early stage of diastolic dysfunction in the cardiometabolic syndrome.

Background and Aim: Diastolic heart failure is a common yet difficult to identify condition. The study's goal was to investigate and link NT-proBNP levels with four classes (grade I to grade IV) of diastolic dysfunction as measured by echocardiography. All patients underwent a thorough clinical examination, blood biochemistry, electrocardiography, chest X-ray, echocardiography, and plasma NT-proBNP testing. Material and Methods: The current study was carried out on 50 DHF patients enrolled from outdoor and indoor patients in the Department of Medicine, Tertiary Care Teaching Institute of India over a one-year period. Clinical assessment and echocardiography were performed on the patients. The autoanalyzer was used to estimate NT-proBNP utilising the electrochemiluminisense method. Echocardiography was used to classify patients into different levels of diastolic dysfunction. Results: The mean levels of NTproBNP in individuals with systemic hypertension were statistically significant (p0.05) higher than in non-hypertensive patients in the current investigation. NT-proBNP levels were observed to be statistically greater in LVH participants compared to those without LVH. (p≤0.05) In the current study of 50 patients with diastolic heart failure, 36 patients (72%) had grade I diastolic dysfunction, 9 patients (18%) had grade II diastolic dysfunction, 3 patients (6%) had a grade III diastolic dysfunction, and 2 patients (3%) had a grade IV diastolic dysfunction. Conclusion: Serum NT-proBNP levels give reliable diagnostic accuracy for detecting diastolic heart failure, and they correlate well with increasing degree of diastolic dysfunction as measured by a well-established modality of echocardiography. In symptomatic individuals, NT-proBNP can accurately detect the presence of isolated diastolic dysfunction and is a valuable diagnostic for ruling out patients with impaired exercise tolerance of non-cardiac origin. [ABSTRACT FROM AUTHOR]

Aims: Impaired myocardial energy homeostasis plays an import role in the pathophysiology of heart failure with preserved ejection fraction (HFpEF). Left ventricular relaxation has a high energy demand, and left ventricular diastolic dysfunction has been related to impaired energy homeostasis. This study investigated whether trimetazidine, a fatty acid oxidation inhibitor, could improve myocardial energy homeostasis and consequently improve exercise haemodynamics in patients with HFpEF. Methods and results: The DoPING‐HFpEF trial was a phase II single‐centre, double‐blind, placebo‐controlled, randomized cross‐over trial. Patients were randomized to trimetazidine treatment or placebo for 3 months and switched after a 2‐week wash‐out period. The primary endpoint was change in pulmonary capillary wedge pressure, measured with right heart catheterization at multiple stages of bicycling exercise. Secondary endpoint was change in myocardial phosphocreatine/adenosine triphosphate, an index of the myocardial energy status, measured with phosphorus‐31 magnetic resonance spectroscopy. The study included 25 patients (10/15 males/females; mean (standard deviation) age, 66 (10) years; body mass index, 29.8 (4.5) kg/m2); with the diagnosis of HFpEF confirmed with (exercise) right heart catheterization either before or during the trial. There was no effect of trimetazidine on the primary outcome pulmonary capillary wedge pressure at multiple levels of exercise (mean change 0 [95% confidence interval, 95% CI −2, 2] mmHg over multiple levels of exercise, P = 0.60). Myocardial phosphocreatine/adenosine triphosphate in the trimetazidine arm was similar to placebo (1.08 [0.76, 1.76] vs. 1.30 [0.95, 1.86], P = 0.08). There was no change by trimetazidine compared with placebo in the exploratory parameters: 6‐min walking distance (mean change of −6 [95% CI −18, 7] m vs. −5 [95% CI −22, 22] m, respectively, P = 0.93), N‐terminal pro‐B‐type natriuretic peptide (5 (−156, 166) ng/L vs. −13 (−172, 147) ng/L, P = 0.70), overall quality‐of‐life (KCCQ and EQ‐5D‐5L, P = 0.78 and P = 0.51, respectively), parameters for diastolic function measured with echocardiography and cardiac magnetic resonance, or metabolic parameters. Conclusions: Trimetazidine did not improve myocardial energy homeostasis and did not improve exercise haemodynamics in patients with HFpEF. [ABSTRACT FROM AUTHOR]

Diastolic dysfunction refers to a structural or functional abnormality of the left ventricle, resulting in impaired filling of the heart. Severe diastolic dysfunction can lead to congestive heart failure even when the left ventricle systolic function is normal. Heart failure with preserved ejection fraction (HFpEF) accounts for nearly half of the hospitalizations for acute heart failure in the adult population but the clinical recognition and understanding of HFpEF in children is poor. The condition is certainly much less frequent than in the adult population but the confirmatory diagnosis of diastolic dysfunction in children is also challenging. The underlying causes of HFpEF in children are diverse and differ from the main cause in adults. This review addresses the underlying causes and prognostic factors of HFpEF in children. We describe the pulmonary hypertension profiles associated with this cardiac condition. We discuss diagnosis difficulties in clinical practice, and we provide a simplified diagnostic algorithm for HFpEF in children.

Aims: Heart failure (HF) with preserved ejection fraction (HFpEF) is associated with cardiovascular (CV) and non‐CV events, but long‐term risk is poorly studied. We assessed incidence and predictors of the long‐term CV and non‐CV events. Methods and results: Patients presenting with acute HF, EF ≥ 45%, and N‐terminal pro‐brain natriuretic peptide > 300 ng/L were enrolled in the Karolinska‐Rennes study in 2007–11 and were reassessed after 4–8 weeks in a stable state. Long‐term follow‐up was conducted in 2018. The Fine–Gray sub‐distribution hazard regression was used to detect predictors of CV and non‐CV deaths, investigated separately from baseline acute presentation (demographic data only) and from the 4–8 week outpatient visit (including echocardiographic data). Of 539 patients enrolled [median age 78 (interquartile range: 72–84) years; 52% female], 397 patients were available for the long‐term follow‐up. Over a median follow‐up time from acute presentation of 5.4 (2.1–7.9) years, 269 (68%) patients died, 128 (47%) from CV and 120 (45%) from non‐CV causes. Incidence rates per 1000 patient‐years were 62 [95% confidence interval (CI) 52–74] for CV and 58 (95% CI 48–69) for non‐CV death. Higher age and coronary artery disease (CAD) were independent predictors of CV death, and anaemia, stroke, kidney disease, and lower body mass index (BMI) and sodium concentrations of non‐CV death. From the stable 4–8 week visit, anaemia, CAD, and tricuspid regurgitation (>3.1 m/s) were independent predictors of CV death, and higher age of non‐CV death. Conclusions: In patients with acute decompensated HFpEF, over 5 years of follow‐up, nearly two‐thirds of patients died, half from CV and the other half from non‐CV causes. CAD and tricuspid regurgitation were associated with CV death. Stroke, kidney disease, lower BMI, and lower sodium were associated with non‐CV death. Anaemia and higher age were associated with both outcomes. [Correction added on 24 March 2023, after first online publication: In the first sentence of the Conclusions, 'two‐thirds' has been inserted before 'of patients died...' in this version.] [ABSTRACT FROM AUTHOR]

Background and aims Heart failure with preserved ejection fraction (HFpEF) is a syndrome with a heterogeneous presentation. This study provides an in-;depth description of haemodynamic and metabolic alterations revealed by systematic assessment through cardiopulmonary exercise testing combined with exercise echocardiography (CPETecho) within a dedicated dyspnoea clinic. Methods and results Consecutive patients (n = 297), referred to a dedicated dyspnoea clinic using a standardized workup including CPETecho, with HFpEF diagnosed through a H2FPEF score ≥6 or HFA-PEFF score ≥5, were evaluated. A median of four haemodynamic/metabolic alterations was uncovered per patient: impaired stroke volume reserve (73%), impaired chronotropic reserve (72%), exercise pulmonary hypertension (65%), and impaired diastolic reserve (64%) were the most frequent cardiac alterations. Impaired peripheral oxygen extraction and a ventilatory limitation were present in 40% and 39%, respectively. In 267 patients (90%), 575 further diagnostic examinations were recommended (median of two tests per patient). Cardiac magnetic resonance imaging, coronary or amyloidosis workup, ventilation–perfusion scanning, and pulmonology referral were each recommended in approximately one out of three patients. In 293 patients (99%), 929 cardiovascular drug optimizations were performed (median of 3 modifications per patient). In 110 patients (37%), 132 cardiovascular interventions were performed, with ablation as the most frequent procedure. Conclusion Holistic workup of HFpEF patients within a multidisciplinary, dedicated dyspnoea clinic, including systematic implementation of CPETecho reveals various haemodynamic/metabolic alterations, leading to further diagnostic testing and potential treatment changes in the majority of cases. [ABSTRACT FROM AUTHOR]

Background/Aims: Nonalcoholic fatty liver disease (NAFLD) encompasses a range of diseases from nonalcoholic fatty liver (NAFL) to nonalcoholic steatohepatitis (NASH) and has been linked to cardiovascular disease and sub-clinical cardiac remodeling. This paper presents a retrospective study of biopsy-proven NAFL and NASH to examine the differences in subclinical cardiac remodeling. Methods: Patients were recruited from an institutional repository of patients with liver-biopsy-confirmed NAFLD. Patients with a transthoracic echocardiogram (TTE) within 12 months of the liver biopsy were included. The parameters of the diastolic dysfunction were reviewed for the differences between NAFL and NASH as well as between the stages and grades of NASH. Results: Thirty-three patients were included in the study, 17 with NAFL and 16 with NASH. The NASH patients were more likely to have lower platelets, higher AST, higher ALT, and higher rates of type 2 diabetes mellitus, coronary artery disease, and hypertension than the NAFL patients. The E/e’ ratio on transthoracic echocardiogram was significantly higher in NASH compared to NAFL, advanced-stage NASH compared to early stage, and high-grade NASH compared to low-grade. The E/e’ ratio was also significantly higher in NASH than NAFL in patients without diabetes mellitus. The presence of diastolic dysfunction trended toward significance. The other markers of diastolic dysfunction were similar. Logistic regression revealed a statistical association with E/e' and NASH. Conclusions: NASH patients had evidence of a higher E/e’ ratio than NAFL, and there was a trend towards a significant diastolic dysfunction. Patients with NASH compared to NAFL should be closely monitored for signs and symptoms of cardiac dysfunction.

Diastolic dysfunction (DD) refers to abnormalities in the mechanical function of the left ventricle (LV) during diastole. Severe LVDD can cause symptoms and the signs of heart failure (HF) in the setting of normal or near normal LV systolic function and is referred to as diastolic HF or HF with preserved ejection fraction (HFpEF). Pediatric cardiologists have long speculated HFpEF in children with congenital heart disease and cardiomyopathy. However, understanding the risk factors, clinical course, and validated biomarkers predictive of the outcome of HFpEF in children is challenging due to heterogeneous etiologies and overlapping pathophysiological mechanisms. The natural history of HFpEF varies depending upon the patient's age, sex, race, geographic location, nutritional status, biochemical risk factors, underlying heart disease, and genetic-environmental interaction, among other factors. Pediatric onset HFpEF is often not the same disease as in adults. Advances in the noninvasive evaluation of the LV diastolic function by strain, and strain rate analysis with speckle-tracking echocardiography, tissue Doppler imaging, and cardiac magnetic resonance imaging have increased our understanding of the HFpEF in children. This review addresses HFpEF in children and identifies knowledge gaps in the underlying etiologies, pathogenesis, diagnosis, and management, especially compared to adults with HFpEF. [ABSTRACT FROM AUTHOR]

Genetically engineered pigs are thought to be an alternative organ source for patients in end-stage heart failure unable to receive a timely allograft. However, cardiac xenografts exhibit growth and diastolic heart failure within 1 month after transplantation. Grafts function for up to 6 months, but only after administration of temsirolimus and afterload-reducing agents to reduce this growth. In this study we investigated the growth and hemodynamics of growth hormone receptor (GHR) knockout xenografts, without the use of adjuncts to prevent intrinsic graft growth after transplantation. Genetically engineered pig hearts were transplanted orthotopically into weight-matched baboons between 15 and 30 kg, using continuous perfusion preservation before implantation (n = 5). Xenografts included knockout of carbohydrate antigens and knockin of human transgenes for thromboregulation, complement regulation, and inflammation reduction (grafts with intact growth hormone, n = 2). Three grafts contained the additional knockout of GHR (GHR knockout grafts; n = 3). Transthoracic echocardiograms were obtained twice monthly and comprehensively analyzed by a blinded cardiologist. Hemodynamics were measured longitudinally after transplantation. All xenografts demonstrated life-supporting function after transplantation. There was no difference in intrinsic growth, measured using septal and posterior wall thickness and left ventricular mass, on transthoracic echocardiogram out to 1 month in either GHR knockout or GHR intact grafts. However, hypertrophy of the septal and posterior wall was markedly elevated by 2 months post transplantation. There was minimal hypertrophy out to 6 months in GHR knockout grafts. Physiologic mismatch was present in all grafts after transplantation, which is largely independent of growth. Xenografts with GHR knockout show reduced post-transplantation xenograft growth using echocardiography >6 months after transplantation, without the need for other adjuncts. Post-transplantation xenograft growth is a life-limiting phenomenon in recipients after cardiac xenotransplantation. In this study, genetically engineered hearts expressing multiple human transgenes, with or without intact growth hormone receptor, were transplanted orthotopically into weight-matched baboons after continuous perfusion preservation. Post-transplantation xenograft growth was investigated using echocardiography and physiologic mismatch was characterized. Results indicate markedly elevated heart rates and mean arterial pressures experienced by all transplanted xenografts. Growth hormone intact grafts showed marked post-transplantation xenograft growth compared with those with growth hormone receptor knocked out. This study demonstrates reduced xenograft growth after transplantation by using xenografts with multiple human transgenes and growth hormone receptor knockout. Implications include the possible elimination for the need for adjuncts to reduce post-transplantation cardiac xenograft growth. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: Patients admitted with pneumonia and heart failure (HF) have increased mortality and cost compared to those without HF, but it is not known whether outcomes differ between systolic and diastolic HF. Management of concomitant pneumonia and HF is complicated because HF treatments can worsen complications of pneumonia. Methods: This is a retrospective cohort study from the Premier Database among patients admitted with pneumonia between 2010 and 2015. Patients were categorized based on systolic, diastolic, and combined HF using ICD-9 codes. The primary outcome was in-hospital mortality. Secondary outcomes included use of HF medications, length of stay, cost, intensive care unit (ICU) admission, as well as use of invasive mechanical ventilation (IMV), vasopressors and inotropes. Multivariable logistic regression was used to describe associations of these outcomes with type of HF. Results: Of 123,211 patients with pneumonia and HF, 41,196 (33.4%) had systolic HF, 69,982 (56.8%) diastolic HF, and 12,033 (9.8%) had combined HF. Compared to patients with diastolic HF, after multivariable adjustment systolic HF was associated with higher in-hospital mortality (OR 1.15; 95% CI:1.11–1.20), ICU admission, and use of IMV and vasoactive agents, but not with increased length of stay or cost. Among patients with systolic HF, 80% received a loop diuretic, 72% a beta blocker, 48% angiotensin converting enzyme inhibitor or angiotensin receptor blocker, and 12.5% a mineralocorticoid receptor antagonist. Conclusion: Systolic HF is associated with added risk in pneumonia compared to diastolic HF. There may also be an opportunity to optimize medications in systolic HF prior to discharge.

Background Cancer therapy-related cardiac dysfunction (CTRCD) is defined as a decrease in the left ventricular ejection fraction (LVEF) of >10% to a value below the lower limit of normal or relative reduction in global longitudinal strain (GLS) >15% from baseline after cancer treatment. However, the possibility of the development of isolated diastolic dysfunction has never been considered in the clinical presentation of CTRCD. Case summary An 81-year-old woman was admitted to our institution presenting with prominent bilateral leg oedema, orthopnoea, and 8 kg of weight gain after administration of the anti-human epidermal growth factor receptor 2 (HER-2) antibody, trastuzumab, for HER-2-positive breast cancer. Transthoracic echocardiography showed a preserved LVEF of 62% without a significant reduction in GLS compared with results obtained before anti-HER-2 targeted therapy. Doppler echocardiography distinctly revealed a newly developed significant left ventricular diastolic dysfunction with evidence of elevated filling pressure. After successful achievement of volume reduction, the patient underwent cardiac catheter examination, revealing an elevated pulmonary artery wedge pressure of 18 mmHg. Subsequently, trastuzumab was discontinued and the patient was treated with diuretics, arteriodilators, and venodilators, until the signs and symptoms of heart failure completely disappeared. Discussion In the management of CTRCD, including pretreatment screening, cardiotoxicity monitoring, follow-up after anti-cancer agents, and evaluation of the effectiveness of the therapy, too much emphasis has been paid exclusively to the development of systolic dysfunction; however, perspectives for diastolic dysfunction may be needed. A comprehensive multidisciplinary team approach composed of breast surgeons, oncologists, onco-cardiologists, and echocardiography specialists is required. [ABSTRACT FROM AUTHOR]

Heart failure with preserved ejection fraction (HFpEF) is a challenging disease state that has long been plagued by heterogeneity in diagnostic criteria and underlying etiologies. Due in part to the complexity of defining this disease and the simplistic approach of only studying medications that have shown significant improvement in heart failure with reduced ejection fraction, there have been a multitude of negative trials in this population. In the past few years, however, there have been medications that have finally shown to benefit patients with HFpEF. In particular, the blockbuster class of medications called SGLT2 inhibitors have provided a treatment option that improves outcomes in this group of patients. There is increasing focus on HFpEF research that aims to improve the phenotyping of these patients to more successfully tailor therapy and improve patient outcomes. [ABSTRACT FROM AUTHOR]

Introduction: Heart Failure with Normal Ejection Fraction (HFNEF), also known as Diastolic Heart Failure (DHF), has been well-studied since the past two decades. The signs of HFNEF are signs of heart failure and abnormal ventricular filling pressure with normal systolic function. A Metabolic Syndrome (MS) is a clustering of metabolic risk factors. Cardiovascular disease caused by metabolic syndrome includes vascular and myocardial abnormalities such as diastolic dysfunction and relaxation abnormalities. Aim: To study the association between the timing of menopause and Left Ventricular Diastolic Dysfunction (LVDD) in those with and without MS. Materials And Methods: This cross-sectional study was conducted in the period between December 2021 to June 2022 at the Department of Cardiology in A.C.S Medical College and Hospital, Chennai, Tamil Nadu, India. All female patients that underwent a medical examination were selected for the study. Postmenopausal women without overt heart diseases (such as a history of heart valve disease or myocardial infarction, or a prior LV ejection fraction > 50%) were included. This study included 80 patients grouped into two: those with and without MS. The MS group included 30 subjects divided into two subgroups: those who experienced menopause at or before 50 years of age (early menopause group) and those who experienced menopause at or after 50 years of age (late menopause group). Out of 80, 50 participants were divided into early menopause and late menopause groups among women without MS. This study analyse the evolution of left ventricular diastolic dysfunction (LVDD), assessed by transthoracic echocardiography (TTE), in 80 postmenopausal women with and without MS. Independent t-tests was applied to assess the association between the timing of menopause and LVDD. Results: The mean age was 60±7.3 years in women with MS and 62±8.8 years in women without MS. There were no significant differences in the duration since menopause between the postmenopausal women with and without MS. No significant difference was found between the two groups (early vs. late menopause group) with respect to any diastolic parameter, including Early (E) and Late (A), E/A ratio, and E/e in women with MS. In postmenopausal women without MS, there was a significant difference in diastolic parameters including the A, early diastolic annular velocity (e'), ratio of early diastolic transmittal flow velocity to annular flow velocity was calculated (E/e') between the two groups (early vs. late menopause group). In comparison to patients with MS, patients without the condition had significantly lower early peak mitral inflow velocity (E, p-value=0.019), early diastolic mitral annulus motion velocity (e'-septal, p-value=0.05), late peak mitral inflow velocity ratio (E/A, p-value=0.07), and LV filling pressure values (E/e, p-value=0.02). Conclusion: Early menopause impacts diastolic function in postmenopausal women and LVDD progression in women without MS. LVDD progression in women with MS was unaffected by early menopause. [ABSTRACT FROM AUTHOR]

Heart failure with a preserved ejection fraction (HFpEF), previously known as diastolic heart failure, was first recognized more than 50 years ago. In spite of all the advances in the knowledge of HFpEF, important questions remain, namely the fact that no therapy has been shown to improve outcomes in these patients. The EMPEROR-Preserved Trial, a trial on the use of empagliflozin on patients with HFpEF, published in October 2021, was the first trial to ever show a change in outcomes in these patients. This article reviews the history of HFpEF and the problems related to its definition and diagnosis over time, and critically reviews the results of the EMPEROR-Preserved Trial in light of these. [ABSTRACT FROM AUTHOR]

The ability to distinguish clinically meaningful subtypes of heart failure with preserved ejection fraction (HFpEF) has recently been examined by machine learning techniques but studies appear to have produced discordant results. The objective of this study is to synthesize the types of HFpEF by examining their features and relating them to phenotypes with adverse prognosis. A systematic search was conducted using the search terms “Diastolic Heart Failure” OR “heart failure with preserved ejection fraction” OR “heart failure with normal ejection fraction” OR “HFpEF” AND “machine learning” OR “artificial intelligence” OR ‘computational biology’. Ten studies were identified and they varied in their prevalence of ten clinical variables: age, sex, body mass index (BMI) or obesity, hypertension, diabetes mellitus, coronary artery disease, atrial fibrillation, chronic kidney disease, chronic obstructive pulmonary disease or symptom severity (NYHA class or BNP). The clinical findings associated with the different phenotypes in > 85 % of studies were age, hypertension, atrial fibrillation, chronic kidney disease and worse symptoms severity; an adverse outcome was in 65 % to 85 % of studies identified diabetes mellitus and female sex and in less than 65 % of studies was body mass index or obesity, and coronary artery disease. COPD was a relevant factor in only 33 % of studies. Adverse clinical outcome – death or admission to hospital (for heart failure) defined phenogroups with the worst outcome. Combining the 4 studies that calculated the MAGGIC score showed a significant (p

Background: Heart failure is a common clinical entity which we come across in our daily practice and accounts for significant mortality and morbidity. The basic pathophysiology lies in the inability of the heart to pump adequate blood (output) to meet the demands of circulation/tissue or can do so only at the expense of elevated left ventricular filling pressure. Among various types of heart failure, heart failure with preserved ejection fraction (HFpEF) is still a poorly understood entity and several comorbidities such as hypertension, diabetes, coronary artery disease, obesity, and CKD are common association of HFpEF. Diabetes causes heart failure by increasing the risk of CAD and by direct injury to myocardium (cardiomyopathy). Hence, in this cross-sectional observational study, we assess the cardiovascular risk factors such as hypertension and diabetes mellitus in association with HFpEF. Aims and Objectives: This study aims to establish the hypothesis that hypertension and diabetes mellitus are associated with a predictor of HFpEF. Materials and Methods: Ninety patients were selected. NTproBNP, HbA1C, FBS, PPBS level, and blood pressure was measured and echocardiogram was performed to assess ratio of transmitral flow velocity and annular velocity (E/E’); left ventricular end-diastolic pressure; and left ventricular ejection fraction (LVEF). Results: The mean age was 64±7. Forty-two (46.67%) were men and 48 (53.33%) were female. Hypertension was present in 73 (81.11%) and diabetes in 44 (48.89%). E/E´, a parameter of LV diastolic function, showed positive correlation to both risk factors in study (r=0.653, p

Abstract Background Constrictive pericarditis (CP) is characterized by scarring and loss of elasticity of the pericardium. This case demonstrates that mixed martial arts (MMA) is a previously unrecognized risk factor for CP, diagnosis of which is supported by cardiac imaging, right and left heart catheterization, and histological findings of dense fibrous tissue without chronic inflammation. Case presentation A 47-year-old Caucasian male former mixed martial arts (MMA) fighter from the Western United States presented to liver clinic for elevated liver injury tests (LIT) and a 35-pound weight loss with associated diarrhea, lower extremity edema, dyspnea on exertion, and worsening fatigue over a period of 6 months. Past medical history includes concussion, right bundle branch block, migraine headache, hypertension, chronic pain related to musculoskeletal injuries and fractures secondary to MMA competition. Involvement in MMA was extensive with an 8-year history of professional MMA competition and 13-year history of MMA fighting with recurrent trauma to the chest wall. The patient also reported a 20-year history of performance enhancing drugs including testosterone. Physical exam was notable for elevated jugular venous pressure, hepatomegaly, and trace peripheral edema. An extensive workup was performed including laboratory studies, abdominal computerized tomography, liver biopsy, echocardiogram, and cardiac magnetic resonance imaging. Finally, right and left heart catheterization—the gold standard—confirmed discordance of the right ventricle-left ventricle, consistent with constrictive physiology. Pericardiectomy was performed with histologic evidence of chronic pericarditis. The patient’s hospital course was uncomplicated and he returned to NYHA functional class I. Conclusions CP can be a sequela of recurrent pericarditis or hemorrhagic effusions and may have a delayed presentation. In cases of recurrent trauma, CP may be managed with pericardiectomy with apparent good outcome. Further studies are warranted to analyze the occurrence of CP in MMA so as to better define the risk in such adults.

BackgroundBody temperature (BT) has been used to evaluate the outcomes of patients with various diseases. In this study, patients with diastolic heart failure (DHF) in the intensive care unit (ICU) were examined for a correlation between BT and mortality.MethodsThis was a retrospective cohort study of the Medical Information Mart for Intensive Care (MIMIC)-IV dataset. A total of 4,153 patients with DHF were included. The primary outcomes were 28-day ICU and higher in-hospital mortality rates. BT was used in the analyses both as a continuous variable and as a categorical variable. According to the distribution of BT, the patients were categorized into three groups (hypothermia BT

Introduction: Heart Failure with Normal Ejection Fraction (HFNEF), also known as Diastolic Heart Failure (DHF), has been well-studied since the past two decades. The signs of HFNEF are signs of heart failure and abnormal ventricular filling pressure with normal systolic function. A Metabolic Syndrome (MS) is a clustering of metabolic risk factors. Cardiovascular disease caused by metabolic syndrome includes vascular and myocardial abnormalities such as diastolic dysfunction and relaxation abnormalities. Aim: To study the assosciation between the timing of menopause and Left Ventricular Diastolic Dysfunction (LVDD) in those with and without MS. Materials And Methods: This cross-sectional study was conducted in the period between December 2021 to June 2022 at the Department of Cardiology in A.C.S Medical College and Hospital, Chennai, Tamil Nadu, India. All female patients that underwent a medical examination were selected for the study. Postmenopausal women without overt heart diseases (such as a history of heart valve disease or myocardial infarction, or a prior LV ejection fraction > 50%) were included. This study included 80 patients grouped into two: those with and without MS. The MS group included 30 subjects divided into two subgroups: those who experienced menopause at or before 50 years of age (early menopause group) and those who experienced menopause at or after 50 years of age (late menopause group). Out of 80, 50 participants were divided into early menopause and late menopause groups among women without MS. This study analyse the evolution of left ventricular diastolic dysfunction (LVDD), assessed by transthoracic echocardiography (TTE), in 80 postmenopausal women with and without MS. Independent t-tests was applied to assess the association between the timing of menopause and LVDD. Results: The mean age was 60±7.3 years in women with MS and 62±8.8 years in women without MS. There were no significant differences in the duration since menopause between the postmenopausal women with and without MS. No significant difference was found between the two groups (early vs. late menopause group) with respect to any diastolic parameter, including Early (E) and Late (A), E/A ratio, and E/e in women with MS. In postmenopausal women without MS, there was a significant difference in diastolic parameters including the A, early diastolic annular velocity (e’), ratio of early diastolic transmitral flow velocity to annular flow velocity was calculated (E/e’) between the two groups (early vs. late menopause group). In comparison to patients with MS, patients without the condition had significantly lower early peak mitral inflow velocity (E, p-value=0.019), early diastolic mitral annulus motion velocity (e’-septal, p-value=0.05), late peak mitral inflow velocity ratio (E/A, p-value=0.07), and LV filling pressure values (E/e, p-value=0.02). Conclusion: Early menopause impacts diastolic function in postmenopausal women and LVDD progression in women without MS. LVDD progression in women with MS was unaffected by early menopause.

The study aimed to assess the accuracy of two-dimensional speckle tracking echocardiography (2DSTE) to evaluate the left atrial (LA) function in patients with heart failure. Additionally, if 2DSTE can differentiate accurately between heart failure preserved ejection fraction (HFpEF, HF with mid-range ejection fraction (HFmrEF=EF 41-49%) and heart failure with reduced ejectionfraction (HFrEF= EF≤40%). The study included 186 patients of heart failure who were classified into 74 patients with HFpEF (LVEF≥50%), 56 patients with HFmrEF (LVEF 41-49%), 56 patients with HFrEF (LVEF<40%), and 50 normal matched subjects. B-type natriuretic peptide (BNP) was more than 35 pg/mL for all patients. The conventional echocardiography evaluated left ventricle systolic and diastolic functions. The 2DSTE evaluated the LV global strain (LVGS), and strain and strain rate (SR) in each phase of LA function. LVGS was -19.3±2.3%, -18.0±1.7%, - 16.1±2.0%, and -14.3±2.2 in controls, HFpEF, and HFmrEF, and HFrEF, respectively (p<0.0001); GPALS was 34.1±6.7%, 27.5±4.7%, 21.7±4.8% and 16.9±4.9% in controls, HFpEF, HFmrEF, HFrEF, respectively (p<0.0001); the GPACS was 14.8±4.3%, 12.3±2.2%, 9.7±2.3%, and 7.5±2.6% in controls, HFpEF, HFmrEF, and HFrEF, respectively (p<0.0001); the PALSPACS was 19.4±3%, 15.1±4.4%, 12.0±3.4%, and 9.3±3.3% in controls, HFpEF, HFmrEF, and HFrEF (p<0.0001). Therefore, early LA dysfunction in heart failure can be detected accurately and easily by speckle tracking technique that could be a promising independent tool to better understand of heart failure and its classification. [ABSTRACT FROM AUTHOR]

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The idiopathic pulmonary arterial hypertension (iPAH) phenotype is changing from a predominantly young female patient to an older, frequently obese patient of either sex. Many newly diagnosed iPAH-patients have risk factors for left ventricular diastolic dysfunction (LVDD), possibly affecting management and treatment. To determine whether the H 2 FPEF-score identifies a subgroup of iPAH-patients with blunted response to PAH-targeted treatment. We performed a retrospective analysis of 253 treatment-naïve iPAH-patients (1989-2019) with a confirmed diagnosis after right heart catheterization by a multidisciplinary team. Follow-up RHC measurements were available in 150 iPAH-patients. iPAH-patients were stratified by the H 2 FPEF-score; a score ≥5 identified a higher possibility of (concealed) LVDD. The presence of a high H 2 FPEF-score in incident iPAH-patients rose 30% in thirty years. Patients with a H 2 FPEF-score ≥5 were older, more often male and/or obese, and had more comorbidities than patients with a H 2 FPEF-score ≤1. A high H 2 FPEF-score was associated with worse survival and poor functional capacity. Right ventricular function was equally depressed among iPAH-groups. Imaging and invasive hemodynamic measurements suggested concealed LVDD in iPAH patients with a high H 2 FPEF-score. At follow-up, hemodynamic and functional responses were similar in iPAH-patients with a high or low H 2 FPEF-score. While a high H 2 FPEF-score in iPAH is associated with a worse prognosis and signs of LVDD, hemodynamic and functional responses to PAH treatment are not predicted by the H 2 FPEF-score. [ABSTRACT FROM AUTHOR]

Abstract Aims Heart failure (HF) with preserved ejection fraction (HFpEF) has poor long‐term prognosis. We assessed rates and predictors of outcome 10 years after an acute episode of HF. Methods and results The Karolinska‐Rennes (KaRen) study enrolled HFpEF patients with acute HF, ejection fraction ≥ 45%, and N‐terminal pro‐brain natriuretic peptide > 300 ng/L in 2007–11. Clinical data were collected at enrolment and after 4–8 weeks including detailed echocardiography. Follow‐up data were collected 10 years after study initiation, starting from 6 months after enrolment until 2018 assessed by telephone. Independent predictors of primary (all‐cause mortality or HF hospitalization) and secondary (all‐cause mortality) outcomes were assessed by multivariable Cox regression. Of 539 patients, long‐term follow‐up data were available for 397 patients [52% female; median (interquartile range) age 79 (73, 84) years]. Over a follow‐up of 5.44 (2.06–7.89) years, 1, 3, 5, and 10 year mortality rates were 15%, 31%, 47%, and 74%, respectively, with an incidence rate of 130/1000 patient‐years. The primary outcome was met in 84% of the population, with an incidence rate of 227/1000 patient‐years. The independent predictors of the primary outcome were tricuspid regurgitation peak velocity (m/s) [hazard ratio 1.87 (1.34–2.62)], diabetes mellitus [1.75 (1.11–2.74)], and cancer [1.75 (1.01–3.03)] while female sex was associated with reduced risk [0.64 (0.41–0.98)]. Conclusions In HFpEF, 1, 3, 5, and 10 year mortality was 15%, 31%, 47%, and 74% and mortality or first HF hospitalization was 35%, 54%, 67%, and 84%, respectively. Independent predictors of mortality or HF hospitalization were tricuspid regurgitation peak velocity, diabetes mellitus, cancer, and male sex. In clinical management of HFpEF, attention should be paid to both cardiac and non‐cardiac conditions.

Abstract Background Skeletal muscle (SM) alterations contribute to exercise intolerance in heart failure patients with preserved (HFpEF) or reduced (HFrEF) left ventricular ejection fraction (LVEF). Protein degradation via the ubiquitin‐proteasome‐system (UPS), nuclear apoptosis, and reduced mitochondrial energy supply is associated with SM weakness in HFrEF. These mechanisms are incompletely studied in HFpEF, and a direct comparison between these groups is missing. Methods and results Patients with HFpEF (LVEF ≥ 50%, septal E/e′ > 15 or >8 and NT‐proBNP > 220 pg/mL, n = 20), HFrEF (LVEF ≤ 35%, n = 20) and sedentary control subjects (Con, n = 12) were studied. Inflammatory markers were measured in serum, and markers of the UPS, nuclear apoptosis, and energy metabolism were determined in percutaneous SM biopsies. Both HFpEF and HFrEF showed increased proteolysis (MuRF‐1 protein expression, ubiquitination, and proteasome activity) with proteasome activity significantly related to interleukin‐6. Proteolysis was more pronounced in patients with lower exercise capacity as indicated by peak oxygen uptake in per cent predicted below the median. Markers of apoptosis did not differ between groups. Mitochondrial energy supply was reduced in HFpEF and HFrEF (complex‐I activity: −31% and −53%; malate dehydrogenase activity: −20% and −29%; both P

BackgroundHeart failure (HF) with preserved ejection fraction (HFpEF) is a growing public health burden, with mortality and rehospitalization rates comparable to HF with reduced ejection fraction (HFrEF). The evidence for the clinical usefulness of soluble suppression of tumorigenicity 2 (sST2) in HFpEF is contradictory. Therefore, we conducted the following systematic review and meta-analysis to assess the diagnostic and prognostic value of serum sST2 in HFpEF.MethodsPubMed and Scopus were searched exhaustively from their inception until March 15, 2022. In diagnostic analysis, we compared the diagnostic value of serum sST2 in HFpEF to NT pro-BNP. We separately pooled the unadjusted and multivariate-adjusted hazard ratios (HRs) and the corresponding 95% confidence intervals (CIs) in prognostic analysis.ResultsA total of 16 publications from 2008 to 2021 were examined. The results of this analysis were as follow: Firstly, compared with NT pro-BNP, sST2 obtains poor diagnostic performance in independently identifying HFpEF from healthy controls, hypertensive patients, and HFrEF patient. Nevertheless, it may provide incremental value to other biomarkers for diagnosing HFpEF and deserves further investigation. Secondly, log sST2 was independently associated with adverse endpoints on multivariable analysis after adjusting for variables such as age, sex, race, and NYHA class. Per log unit rise in sST2, there was a 2.76-fold increased risk of all-cause death [HR:2.76; 95% CI (1.24, 6.16); p = 0.516, I2 = 0%; P = 0.013] and a 6.52-fold increased risk in the composite endpoint of all-cause death and HF hospitalization [HR:6.52; 95% CI (2.34, 18.19); p = 0.985, I2 = 0%; P = 0.000]. Finally, the optimal threshold levels of serum sST2 need further determined.ConclusionsHigher sST2 was strongly linked to an increased risk of adverse outcomes in HFpEE. Especially, log sST2 independently predicted all-cause death and the composite endpoint of all-cause death and HF hospitalization. However, prospective and multicenter studies with large-sample and extended follow-up periods are required to validate our results due to limitations in our research.

Background A substantial proportion of patients with heart failure (HF) with preserved ejection fraction (HFpEF) present with normal natriuretic peptide (NP) levels. The pathophysiology and natural history for this phenotype remain unclear. Methods and results Consecutive subjects undergoing invasive cardiopulmonary exercise testing for unexplained dyspnoea at Mayo Clinic in 2006–18 were studied. Heart failure with preserved ejection fraction was defined as a pulmonary arterial wedge pressure (PAWP) ≥15 mmHg (rest) or ≥25 mmHg (exercise). Patients with HFpEF and normal NP [N-terminal of the pro-hormone B-type natriuretic peptide (NT-proBNP) < 125 ng/L] were compared with HFpEF with high NP (NT-proBNP ≥ 125 ng/L) and controls with normal haemodynamics. Patients with HFpEF and normal (n = 157) vs. high NP (n = 263) were younger, yet older than controls (n = 161), with an intermediate comorbidity profile. Normal NP HFpEF was associated with more left ventricular hypertrophy and worse diastolic function compared with controls, but better diastolic function, lower left atrial volumes, superior right ventricular function, and less mitral/tricuspid regurgitation compared with high NP HFpEF. Cardiac output (CO) reserve with exercise was preserved in normal NP HFpEF [101% predicted, interquartile range (IQR): 75–124%], but this was achieved only at the cost of higher left ventricular transmural pressure (LVTMP) (14 ± 6 mmHg vs. 7 ± 4 mmHg in controls, P < 0.001). In contrast, CO reserve was decreased in high NP HFpEF (85% predicted, IQR: 59–109%), with lower LVTMP (10 ± 8 mmHg) compared with normal NP HFpEF (P < 0.001), despite similar PAWP. Patients with high NP HFpEF displayed the highest event rates, but normal NP HFpEF still had 2.7-fold higher risk for mortality or HF readmissions compared with controls (hazard ratio: 2.74, 95% confidence interval: 1.02–7.32) after adjusting for age, sex, and body mass index. Conclusion Patients with HFpEF and normal NP display mild diastolic dysfunction and preserved CO reserve during exercise, despite marked elevation in filling pressures. While clinical outcomes are not as poor compared with patients with high NP, patients with normal NP HFpEF exhibit increased risk of death or HF readmissions compared with patients without HF, emphasizing the importance of this phenotype. [ABSTRACT FROM AUTHOR]

Heart failure (HF) is a major cause of morbidity and mortality worldwide. Current classifications of HF categorize patients with a left ventricular ejection fraction of 50% or greater as HF with preserved ejection fraction or HFpEF. Echocardiography is the first line imaging modality in assessing diastolic function given its practicality, low cost and the utilization of Doppler imaging. However, the last decade has seen cardiac magnetic resonance (CMR) emerge as a valuable test for the sometimes challenging diagnosis of HFpEF. The unique ability of CMR for myocardial tissue characterization coupled with high resolution imaging provides additional information to echocardiography that may help in phenotyping HFpEF and provide prognostication for patients with HF. The precision and accuracy of CMR underlies its use in clinical trials for the assessment of novel and repurposed drugs in HFpEF. Importantly, CMR has powerful diagnostic utility in differentiating acquired and inherited heart muscle diseases presenting as HFpEF such as Fabry disease and amyloidosis with specific treatment options to reverse or halt disease progression. This state of the art review will outline established CMR techniques such as transmitral velocities and strain imaging of the left ventricle and left atrium in assessing diastolic function and their clinical application to HFpEF. Furthermore, it will include a discussion on novel methods and future developments such as stress CMR and MR spectroscopy to assess myocardial energetics, which show promise in unraveling the mechanisms behind HFpEF that may provide targets for much needed therapeutic interventions.

Background and AimHeart failure in children differs substantially from the adult population. Clinical characteristics of pediatric diastolic heart failure has rarely been reported. In this study, we aimed to summary the causes, clinical features, lab tests, and treatment effect of pediatric diastolic heart failure.MethodsThis study was a single center, retrospective study conducted in Children’s Hospital of Chongqing Medical University. Children who were diagnosed with diastolic heart failure (DHF) without systolic heart failure (SHF) between 2006 and 2014 were included. Meanwhile, SHF (without DHF) cases were also collected from 2013 to 2014.ResultsA total of 421 DHF and 42 SHF cases were included. The average age of pediatric DHF was 1.89 ± 3.29 years old, significant younger than that of SHF (4.65 ± 4.90). The top three cardiovascular causes of DHF were complex congenital heart malformations (53.4%), simple congenital heart defect (15.7%), and cardiomyopathy (7.4%). Alternatively, number of cardiomyopathy cases (57.1%) ranked first in SHF group. Simple congenital heart diseases (CHDs) rarely caused SHF. The most common symptom and sign were tachypnea and hepatomegaly in pediatric HF. Symptoms like cyanosis, feeding difficulty, be fidgety, pale, fatigue, and edema were valuable in differential diagnosis of DHF and SHF in children. B-type natriuretic peptide (BNP) increase was found in 36.9% of DHF children, and 60% in SHF patients. Sensitivity of BNP greater than 100 pg/ml in diagnosis of DHF was 0.37, and specificity of it was 0.86. Diastolic function indicators, such as E/A (early wave/late wave) ratio, IVRT (isovolumic relaxation time) were significant recovered after treatment in DHF patients. Less therapeutic benefits were achieved in children with cardiomyopathy induced DHF, in compared with non-cardiomyopathy patients.ConclusionPediatric DHF and SHF were largely different in primary causes, clinical symptoms and signs and short-term prognosis. There was a limit diagnostic value of BNP with 100 pg/ml as cut-off value in pediatric DHF. Larger, multicenter studies of pediatric DHF are required in the future.

Abstract The impact of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) on diastolic function is less known. We describe a 46‐year‐old man with a history of mild hypertension who presented to the emergency department with fever, cough, and myalgia for 2 days. The patient was tested positive for SARS‐CoV‐2. He was admitted and started on a combination of antiviral and antimicrobial therapy. He developed respiratory distress 2 days later, and O2 saturation declined. Blood tests showed an increased N‐terminal pro‐B type natriuretic peptide (NT‐proBNP) level, and echocardiography showed normal left ventricular ejection fraction and E/e′ ratio of 16. Computed tomography scan showed interstitial pulmonary oedema and prominent peripheral pulmonary vascular markings. Given these findings, heart failure with preserved ejection fraction (HFpEF) was considered. Low‐dose diuretic was started, and fluid administration was restricted, resulting in a decrease in NT‐proBNP level, clinical and haemodynamic stabilization, and improved oxygenation. This case highlights the occurrence of HFpEF in coronavirus disease 2019.

Agata Bielecka-Dabrowa,1,2 Paulina Gasiorek,2 Andrzej Wittczak,2 Agata Sakowicz,3 Ibadete Bytyçi,4,5 Maciej Banach1,2 1Heart Failure Unit, Department of Cardiology and Congenital Diseases of Adults, Polish Mother’s Memorial Hospital Research Institute (PMMHRI), Lodz, Poland; 2Department of Hypertension, Chair of Nephrology and Hypertension, Medical University of Lodz, Lodz, Poland; 3Department of Medical Biotechnology, Medical University of Lodz, Lodz, Poland; 4Clinic of Cardiology, University Clinical Centre of Kosovo, Prishtina, Kosovo; 5Institute of Public Health and Clinical Medicine, Umeå University, Umeå, SwedenCorrespondence: Agata Bielecka-DabrowaHeart Failure Unit¸ Department of Cardiology and Congenital Diseases of Adults, Polish Mother’s Memorial Hospital Research Institute (PMMHRI), Rzgowska 281/289, Lodz, 93-338, PolandTel +48 42 271 15 97Fax +48 42 271 15 91Email agatbiel7@poczta.onet.plObjective: Identification of echocardiographic, hemodynamic and biochemical predictors of unfavorable prognosis after embolic strokes of undetermined etiology (ESUS) in patients at age < 65.Patients and Methods: Out of 520 ischemic stroke patients we selected 64 diagnosed with ESUS and additional 36 without stroke but with similar risk profile. All patients underwent echocardiography, non-invasive assessment of hemodynamic parameters using SphygmoCor tonometer and measurements of selected biomarkers. Follow-up time was 12 months.Results: Nine percent of patients died, and recurrent ischemic stroke occurred in 9% of patients only in the ESUS group. Atrial fibrillation (AF) occurred in 10% of patients and the ESUS group had a significantly poorer outcome of AF in the first 2 months after hospitalization. The outcome of re-hospitalization was 28% in the ESUS group and 17% in the control group. In the multivariate analysis mean early diastolic (E’) mitral annular velocity (OR 0.75, 95% CI: 0.6– 0.94; p=0.01) was significantly associated with cardiovascular hospitalizations. The only independent predictor of recurrent stroke was the ratio of peak velocity of early diastolic transmitral flow to peak velocity of early diastolic mitral annular motion (E/E’) (OR 0.75, 95% CI: 0.6– 0.94; p=0.01). E/E’ was independently associated with composite endpoint (death, hospitalization and recurrent stroke) (OR 1.90, 95% CI 1.1– 3.2, p=0.01).Conclusion: The indices of diastolic dysfunction are significantly associated with unfavorable prognosis after ESUS. There is a robust role for outpatient cardiac monitoring especially during the first 2 months after ESUS to detect potential AF.Keywords: ischemic stroke of undetermined etiology, atrial fibrillation, diastolic heart failure, diastolic dysfunction

Left ventricular diastolic dysfunction (LVDD) has been observed in people with nonalcoholic fatty liver disease (NAFLD) in cross-sectional studies but the causal relationship is unclear. This study aimed to investigate the impact of NAFLD and the fibrotic progression of the disease on the development of LVDD, assessed by serial echocardiography, in a large population over a 7-year longitudinal setting. This retrospective cohort study included the data of 3,380 subjects from a medical health check-up program. We defined subjects having NAFLD by abdominal ultrasonography and assessed significant liver fibrosis by the aspartate transaminase (AST) to platelet ratio index (APRI), the NAFLD fibrosis score (NFS), and the fibrosis-4 (FIB-4) index. LVDD was defined using serial echocardiography. A parametric Cox proportional hazards model was used. During 11,327 person-years of follow-up, there were 560 (16.0 %) incident cases of LVDD. After adjustment for multiple risk factors, subjects with NAFLD showed an increased adjusted hazard ratio (aHR) of 1.21 (95 % confidence interval [CI]=1.02–1.43) for incident LVDD compared to those without. The risk of LV diastolic dysfunction increased progressively with increasing degree of hepatic steatosis (P < 0.001). Compared to subjects without NAFLD, the multivariable-aHR (95 % CI) for LVDD in subjects with APRI < 0.5 and APRI ≥ 0.5 were 1.20 (1.01–1.42) and 1.36 (0.90–2.06), respectively (P = 0.036), while other fibrosis prediction models (NFS and FIB-4 index) showed insignificant results. This study demonstrated that NAFLD was associated with an increased risk of LVDD in a large cohort. More severe forms of hepatic steatosis and/or significant liver fibrosis may increase the risk of developing LVDD. [ABSTRACT FROM AUTHOR]