Hospitalizaciones y eventos por insuficiencia cardiaca sistólica y diastólica en España entre 2016 y 2019. Un estudio de base poblacional / Hospital admissions and outcomes for systolic and diastolic heart failure in Spain between 2016 and 2019: A population-based study

Antecedentes y objetivos: En España carecemos de datos poblacionales de hospitalizaciones por insuficiencia cardiaca (IC) según sea sistólica o diastólica. Analizamos las diferencias clínicas, en mortalidad intrahospitalaria y reingresos de causa cardiovascular a los 30 días entre ambos tipos. Métodos: Estudio observacional retrospectivo de pacientes dados de alta con el diagnóstico principal de IC de los hospitales del Sistema Nacional de Salud entre 2016 y 2019, distinguiendo entre IC sistólica y diastólica. La fuente de datos fue el conjunto mínimo básico de datos del Ministerio de Sanidad. Se calcularon las razones de mortalidad intrahospitalaria y de reingreso a los 30 días estandarizadas por riesgo usando sendos modelos de regresión logística multinivel de ajuste de riesgo. Resultados: Se seleccionaron 190.200 episodios de IC. De ellos, 163.727 (86,1%) fueron por IC diastólica y se caracterizaron por presentar mayor edad, mayor proporción de mujeres, de diabetes y de insuficiencia renal que los de IC sistólica. Según los modelos de ajuste de riesgo la IC diastólica, frente a la sistólica, se comportó como un factor protector de mortalidad intrahospitalaria (odds ratio [OR]: 0,79; intervalo de confianza del 95% [IC 95%]: 0,75-0,83; p<0,001) y de reingreso de causa cardiovascular a los 30 días (OR: 0,93; IC 95%: 0,88-0,97; p0,002). Conclusiones: En España, entre 2016 y 2019, los episodios de hospitalización por IC fueron mayoritariamente por IC diastólica. Según los modelos de ajuste de riesgo la IC diastólica, con respecto a la sistólica, fue un factor protector de mortalidad intrahospitalaria y de reingreso de causa cardiovascular a los 30 días.(AU)

Background and purpose: In Spain there is a lack of population data that specifically compare hospitalization for systolic and diastolic heart failure (HF). We assessed clinical characteristics, in-hospital mortality and 30-day cardiovascular readmission rates differentiating by HF type. Methods: We conducted a retrospective observational study of patients discharged with the principal diagnosis of HF from The National Health System’ acute hospital during 2016-2019, distinguishing between systolic and diastolic HF. The source of the data was the Minimum Basic Data Set. The risk-standardized in-hospital mortality ratio and risk-standardized 30-day cardiovascular readmission ratio were calculated using multilevel risk adjustment models. Results: The 190,200 episodes of HF were selected. Of these, 163,727 (86.1%) were classified as diastolic HF and were characterized by older age, higher proportion of women, diabetes mellitus, dementia and renal failure than those with systolic HF. In the multilevel risk adjustment models, diastolic HF was a protective factor for both in-hospital mortality (odds ratio [OR]: 0.79; 95% confidence interval [CI]: 0.75-0.83; P<.001) and 30-day cardiovascular readmission versus systolic HF (OR: 0.93; 95% CI: 0.88-0.97; P=.002). Conclusions: In Spain, between 2016 and 2019, hospitalization episodes for HF were mostly due to diastolic HF. According to the multilevel risk adjustment models, diastolic HF compared to systolic HF was a protective factor for both in-hospital mortality and 30-day cardiovascular readmission.(AU)

Myofilament dysfunction in diastolic heart failure.

Diastolic heart failure (DHF), in which impaired ventricular filling leads to typical heart failure symptoms, represents over 50% of all heart failure cases and is linked with risk factors, including metabolic syndrome, hypertension, diabetes, and aging. A substantial proportion of patients with this disorder maintain normal left ventricular systolic function, as assessed by ejection fraction. Despite the high prevalence of DHF, no effective therapeutic agents are available to treat this condition, partially because the molecular mechanisms of diastolic dysfunction remain poorly understood. As such, by focusing on the underlying molecular and cellular processes contributing to DHF can yield new insights that can represent an exciting new avenue and propose a novel therapeutic approach for DHF treatment. This review discusses new developments from basic and clinical/translational research to highlight current knowledge gaps, help define molecular determinants of diastolic dysfunction, and clarify new targets for treatment.

Dilemas de la insuficiencia cardíaca con fracción de eyección preservada / Dilemmas of heart failure with preserved ejection fraction / Dilemas da insuficiência cardíaca com fração de ejeção preservada

La insuficiencia cardíaca con fracción de eyección preservada (ICFEp) y reducida presentan marcadas diferencias. Mientras que la última tiene un algoritmo diagnóstico y terapéutico desde hace años, con guías y fármacos que mejoran su pronóstico, la ICFEp no solo presenta dificultades para llegar al diagnóstico, sino que tampoco hay fármacos que hayan demostrado disminuir la mortalidad. En esta revisión se hace un abordaje amplio de la ICFEp, comenzando por definirla y distinguirla de la disfunción diastólica. Se describe el gold standard para su diagnóstico invasivo y se analizan los scores no invasivos recientemente desarrollados que estiman la probabilidad de tener la enfermedad. A través del análisis de las comorbilidades frecuentemente asociadas, se describen los mecanismos fisiopatológicos implicados. Asimismo, se detallan los fenotipos propuestos para agrupar pacientes y diseñar ensayos clínicos con fármacos que prueben disminuir la mortalidad. Por último, se reseñan las medidas terapéuticas no farmacológicas y farmacológicas recomendadas.

Heart failure with preserved and reduced ejection fraction have significant differences. While the latter has had a diagnostic and therapeutic algorithm for years, with guidelines and drugs that improve its prognosis, heart failure with preserved ejection fraction (HFpEF) not only presents difficulties in reaching a diagnosis, but also there are no drugs that have been proven to be effective in reducing mortality. In this review, a broad approach to HFpEF is made, beginning by defining it and distinguishing it from diastolic dysfunction. The gold standard for its invasive diagnosis is described and recently developed non-invasive scores that estimate the probability of having the disease are analyzed. Through the analysis of the frequently associated comorbidities, the pathophysiological mechanisms involved are described. Likewise, the phenotypes proposed to group patients and design clinical trials with drugs that try to reduce mortality are detailed. Finally, the recommended non-pharmacological and pharmacological therapeutic measures are outlined.

A insuficiência cardíaca com fração de ejeção preservada (ICFEp) e reduzida apresentam diferenças marcantes. Enquanto esta última conta com um algoritmo diagnóstico e terapêutico há anos, com diretrizes e medicamentos que melhoram seu prognóstico, a ICFEp não só apresenta dificuldades no diagnóstico, mas nenhum há medicamentos que tenham demonstrado reduzir a mortalidade. Nesta revisão, é feita uma abordagem ampla da ICFEp, começando por defini-la e distinguindo-a da disfunção diastólica. O padrão ouro para seu diagnóstico invasivo é descrito e são analisados os escores não invasivos recentemente desenvolvidos que estimam a probabilidade de ter a doença. Através da análise de comorbidades frequentemente associadas, são descritos os mecanismos fisiopatológicos envolvidos. Da mesma forma, são detalhados os fenótipos propostos para agrupar pacientes e desenhar ensaios clínicos com medicamentos que podem ser mostradas para reduzir a mortalidade. Por fim, são delineadas as medidas terapêuticas não farmacológicas e farmacológicas recomendadas.

[Update on diastolic heart failure]. / Update zur diastolisch bedingten Herzinsuffizienz.

In August 2021, an update of the European Society of Cardiology-Heart Failure Association guideline for the diagnosis and treatment of heart failure was released. To review the changes implied by current guidelines regarding the diagnosis and treatment of patients with heart failure and preserved left ventricular ejection fraction (HFpEF). The diagnosis of HFpEF requires the combined presence of clinical signs, left ventricular ejection fraction ≥ 50%, elevated natriuretic peptides, and elevated left ventricular filling pressure. If the diagnosis remains equivocal, a stress test is recommended. The targeted identification and treatment of comorbid conditions is key for a holistic therapeutic approach to HFpEF. Diuretics are recommended in congested patients with HFpEF in order to alleviate signs and symptoms. The treatment of diabetic patients with heart failure should include a sodium glucose co-transporter­2 (SGLT2) inhibitor. All patients with HFpEF should be enrolled in a multidisciplinary heart failure management program aiming to improve self-care strategies and offer participation in an exercise program. It was recently shown for the first time in a randomized trial that hard clinical endpoints could be reduced in patients with HFpEF using the SGLT2 inhibitor empagliflozin. It is expected that this finding will become part of updated treatment recommendations in the near future. Although challenging, the early diagnosis of HFpEF is key to averting the poor prognosis associated with this frequent condition. Multidisciplinary care and innovative pharmacologic and non-pharmacologic therapies, however, can improve quality of life, exercise tolerance, and prognosis.

Retrospective Study of 573 Patients with Heart Failure Evaluated for Coronary Artery Disease at Toulouse University Center, France.

BACKGROUND Heart failure (HF) most commonly occurs due to ischemic heart disease from stenotic coronary artery disease (CAD). HF is classified into 3 groups based on the percentage of the ejection fraction (EF): reduced (HFrEF), mid-range (HFmrEF), and preserved (HFpEF). This retrospective study included 573 patients who presented with HF based on the evaluation of EF and were evaluated for CAD by coronary angiography before undergoing coronary angioplasty at a single center in Toulouse, France. MATERIAL AND METHODS This retrospective observational study included patients recently diagnosed with HF or acute decompensation of chronic HF and referred for coronary angiography at Toulouse University Hospital between January 2019 and May 2020. RESULTS Significant CAD was found in 55.8%, 55%, and 55% of the whole population, HFpEF, and HFrEF groups, respectively. Older age, male sex, and diabetes mellitus were the main risk factors for ischemic HF. Except for age and sex, patients with ischemic HFpEF were comparable to those with non-ischemic HFpEF, unlike the ischemic HFrEF group, which had more common cardiovascular risk factors than the non-ischemic HFrEF group. The ischemic HFpEF group had an older age and higher rate of dyslipidemia than the ischemic HFrEF group. CONCLUSIONS At our center, CAD was diagnosed in more than half of patients who presented with heart failure with preserved or reduced EF. Older age and male sex were the common risk factors in patients with HFpEF and HFrEF.

Diastolic and systolic left ventricular dysfunction and mortality in chronic kidney disease patients on haemodialysis.

AIMS: Left ventricular diastolic dysfunction (LVDD) and LV systolic dysfunction (LVSD) are prevalent in CKD, but their prognostic relevance is debatable. We intent to verify whether LVDD and LVSD are independently predictive of all-cause mortality and if they have comparable or different effects on outcomes. METHODS: A retrospective analysis was conducted of the echocardiographic data of 1285 haemodialysis patients followed up until death or transplantation. LVDD was classified into 4 grades of severity. Endpoint was all-cause mortality. RESULTS: During a follow-up of 30 months, 419/1285 (33%) patients died, 224 (53%) due to CV events. LVDD occurred in 75% of patients, grade 1 DD was the prevalent diastolic abnormality, and pseudonormal pattern was the predominant form of moderate-severe DD. Moderate-severe LVDD (HR 1.379, CI% 1.074-1.770) and LVSD (HR 1.814, CI% 1.265-2.576) independently predicted death; a graded, progressive association was found between LVDD categories and the risk of death; and the impact of isolated severe-moderate LVDD on the risk of death was comparable to that exercised by isolated compromised LV systolic function. CONCLUSION: Moderate-severe LVDD and LVSD were independently associated with a higher probability of death and had a similar impact on survival. A progressive association was observed between LVDD grades and mortality.

Energetic Basis for Exercise-Induced Pulmonary Congestion in Heart Failure With Preserved Ejection Fraction.

BACKGROUND: Transient pulmonary congestion during exercise is emerging as an important determinant of reduced exercise capacity in heart failure with preserved ejection fraction (HFpEF). We sought to determine whether an abnormal cardiac energetic state underpins this process. METHODS: We recruited patients across the spectrum of diastolic dysfunction and HFpEF (controls, n=11; type 2 diabetes, n=9; HFpEF, n=14; and severe diastolic dysfunction attributable to cardiac amyloidosis, n=9). Cardiac energetics were measured using phosphorus spectroscopy to define the myocardial phosphocreatine to ATP ratio. Cardiac function was assessed by cardiovascular magnetic resonance cine imaging and echocardiography and lung water using magnetic resonance proton density mapping. Studies were performed at rest and during submaximal exercise using a magnetic resonance imaging ergometer. RESULTS: Paralleling the stepwise decline in diastolic function across the groups (E/e' ratio; P<0.001) was an increase in NT-proBNP (N-terminal pro-brain natriuretic peptide; P<0.001) and a reduction in phosphocreatine/ATP ratio (control, 2.15 [2.09, 2.29]; type 2 diabetes, 1.71 [1.61, 1.91]; HFpEF, 1.66 [1.44, 1.89]; cardiac amyloidosis, 1.30 [1.16, 1.53]; P<0.001). During 20-W exercise, lower left ventricular diastolic filling rates (r=0.58; P<0.001), lower left ventricular diastolic reserve (r=0.55; P<0.001), left atrial dilatation (r=-0.52; P<0.001), lower right ventricular contractile reserve (right ventricular ejection fraction change, r=0.57; P<0.001), and right atrial dilation (r=-0.71; P<0.001) were all linked to lower phosphocreatine/ATP ratio. Along with these changes, pulmonary proton density mapping revealed transient pulmonary congestion in patients with HFpEF (+4.4% [0.5, 6.4]; P=0.002) and cardiac amyloidosis (+6.4% [3.3, 10.0]; P=0.004), which was not seen in healthy controls (-0.1% [-1.9, 2.1]; P=0.89) or type 2 diabetes without HFpEF (+0.8% [-1.7, 1.9]; P=0.82). The development of exercise-induced pulmonary congestion was associated with lower phosphocreatine/ATP ratio (r=-0.43; P=0.004). CONCLUSIONS: A gradient of myocardial energetic deficit exists across the spectrum of HFpEF. Even at low workload, this energetic deficit is related to markedly abnormal exercise responses in all 4 cardiac chambers, which is associated with detectable pulmonary congestion. The findings support an energetic basis for transient pulmonary congestion in HFpEF.

Clinical performance and exercise hemodynamics in patients with severe secondary tricuspid regurgitation and chronic atrial fibrillation.

OBJECTIVE: The study aimed to investigate the functional capacity and hemodynamics at rest and during exercise in patients with chronic atrial fibrillation and severe functional symptomatic tricuspid regurgitation (AF-FTR). BACKGROUND: Symptoms and clinical performance of severe AF-FTR mimic the population of patients with heart failure with preserved ejection fraction (HFpEF). Severe AF-FTR is known to be associated with an adverse prognosis whereas less is reported about the clinical performance including exercise capacity and hemodynamics in patients symptomatic AF-FTR. METHODS: Right heart catheterization (RHC) at rest and during exercise was conducted in a group of patients with stable chronic AF-TR and compared with a group of patients with HFpEF diagnosed with cardiac amyloid cardiomyopathy (CA). All patients had preserved ejection fraction and no significant left-sided disease. RESULTS: Patients with AF-FTR demonstrated a low exercise capacity that was comparable to CA patients (TR 4.9 ± 1.2 METS vs. CA 4. 7 ± 1.5 METS; P = 0.78) with an average peak maximal oxygen consumption of 15 mL/min/kg. Right atrium pressure increased significantly more in the AF-FTR patients as compared to CA patients at peak exercise (25 ± 8 vs 19 ± 9, p < 0.01) whereas PCWP increased significantly to a similar extent in both groups (31 ± 4 vs 31 ± 8 mmHg, p = 0.88). Cardiac output (CO) was significantly lower among AF-FTR at rest as compared to CA patients (3.6 ± 0.9 vs 4.4 ± 1.3 l/min; p < 0.05) whereas both groups demonstrated a poor but comparable CO reserve at peak exercise (7.3 ± 2.9 vs 7.9 ± 3.8 l/min, p = 0.59). CONCLUSIONS: AF-FTR contributes to the development of advanced heart failure symptoms and poor exercise capacity reflected in increased atrial filling pressures, reduced cardiac output at rest and during exercise sharing common features seen in HFpEF patients with other etiologies.

Prognostic relevance of elevated plasma osmolality on admission in acute decompensated heart failure with preserved ejection fraction: insights from PURSUIT-HFpEF registry.

BACKGROUND: Complicated pathophysiology makes it difficult to identify the prognosis of heart failure with preserved ejection fraction (HFpEF). While plasma osmolality has been reported to have prognostic importance, mainly in heart failure with reduced ejection fraction (HFrEF), its prognostic meaning for HFpEF has not been elucidated. METHODS: We prospectively studied 960 patients in PURSUIT-HFpEF, a multicenter observational study of acute decompensated HFpEF inpatients. We divided patients into three groups according to the quantile values of plasma osmolality on admission. During a follow-up averaging 366 days, we examined the primary composite endpoint of cardiac mortality or heart failure re-admission using Kaplan-Meier curve analysis and Cox proportional hazard testing. RESULTS: 216 (22.5%) patients reached the primary endpoint. Kaplan-Meier curve analysis revealed that the highest quantile of plasma osmolality on admission (higher than 300.3 mOsm/kg) was significantly associated with adverse outcomes (Log-rank P = 0.0095). Univariable analysis in the Cox proportional hazard model also revealed significantly higher rates of adverse outcomes in the higher plasma osmolality on admission (hazard ratio [HR] 7.29; 95% confidence interval [CI] 2.25-23.92, P = 0.0009). Multivariable analysis in the Cox proportional hazard model also showed that higher plasma osmolality on admission was significantly associated with adverse outcomes (HR 5.47; 95% CI 1.46-21.56, P = 0.0113) independently from other confounding factors such as age, gender, comorbid of atrial fibrillation, hypertension history, diabetes, anemia, malnutrition, E/e', and N-terminal pro-B-type natriuretic peptide elevation. CONCLUSIONS: Higher plasma osmolality on admission was prognostically important for acute decompensated HFpEF inpatients.

Impact of etiology on force and kinetics of left ventricular end-stage failing human myocardium.

BACKGROUND: Heart failure (HF) is associated with highly significant morbidity, mortality, and health care costs. Despite the significant advances in therapies and prevention, HF remains associated with poor clinical outcomes. Understanding the contractile force and kinetic changes at the level of cardiac muscle during end-stage HF in consideration of underlying etiology would be beneficial in developing targeted therapies that can help improve cardiac performance. OBJECTIVE: Investigate the impact of the primary etiology of HF (ischemic or non-ischemic) on left ventricular (LV) human myocardium force and kinetics of contraction and relaxation under near-physiological conditions. METHODS AND RESULTS: Contractile and kinetic parameters were assessed in LV intact trabeculae isolated from control non-failing (NF; n = 58) and end-stage failing ischemic (FI; n = 16) and non-ischemic (FNI; n = 38) human myocardium under baseline conditions, length-dependent activation, frequency-dependent activation, and response to the ß-adrenergic stimulation. At baseline, there were no significant differences in contractile force between the three groups; however, kinetics were impaired in failing myocardium with significant slowing down of relaxation kinetics in FNI compared to NF myocardium. Length-dependent activation was preserved and virtually identical in all groups. Frequency-dependent activation was clearly seen in NF myocardium (positive force frequency relationship [FFR]), while significantly impaired in both FI and FNI myocardium (negative FFR). Likewise, ß-adrenergic regulation of contraction was significantly impaired in both HF groups. CONCLUSIONS: End-stage failing myocardium exhibited impaired kinetics under baseline conditions as well as with the three contractile regulatory mechanisms. The pattern of these kinetic impairments in relation to NF myocardium was mainly impacted by etiology with a marked slowing down of kinetics in FNI myocardium. These findings suggest that not only force development, but also kinetics should be considered as a therapeutic target for improving cardiac performance and thus treatment of HF.

Improvement of Shen'ge formula on heart function in diastolic heart failure: A protocol for randomized, double-blind, placebo-controlled clinical study.

INTRODUCTION: Diastolic heart failure (DHF) is an important pathological type of heart failure, that involves multiple organ dysfunction and multiple complications. The prevalence of DHF is high, and effective treatments are lacking. Chinese herbs are an alternative therapy for DHF. Shen'ge formula (SGF) is a classical formula from which patients can benefit, but convincing evidence of its efficacy is lacking. Therefore, we designed this randomized controlled trial protocol. METHODS/DESIGN: This randomized, double-blind, placebo-controlled clinical trial will evaluate the efficacy and safety of SGF in the treatment of DHF. A total of 130 patients with DHF will be enrolled in the trial and treated with SGF granules or placebo for 12 weeks and followed up for 12 weeks. The primary outcome measurement will be to changes in plasma N-terminal brain natriuretic peptide precursor before versus after treatment, while the second primary outcome measurement will be changes in heart function before versus after treatment and the 12-week follow-up period. It will also include echocardiography, a cardiopulmonary exercise test, cardiac function grading, traditional Chinese medicine syndrome score, and the Minnesota Heart Failure Quality of Life Scale. Adverse events will be evaluated throughout the trial. DISCUSSION: The results of this trial will demonstrate whether SGF could alleviate symptoms, improve cardiac function, reduce readmission rates, and improve quality of life of patients with DHF. TRIAL REGISTRATION: Chinese Clinical Trial Register, ChiCTR2000036533, registered on August 24, 2020.

Transcatheter Interatrial Shunts for the Treatment of Heart Failure with Preserved Ejection Fraction

Abstract Heart failure with preserved ejection fraction (HFpEF) is a clinical syndrome, which accounts for about 50% of patients with heart failure (HF). The morbidity and mortality associated with HFpEF is similar to HFrEF. Clinical trials to date have failed to show a benefit of medical therapy for HFpEF, which may due to lack of uniform phenotypes and heterogeneous population. In addition, medical therapy proven for HFrEF may not address the pathophysiologic basis for HFpEF. Left atrial remodeling and dysfunction is central to HFpEF and accounts for secondary pulmonary hypertension and pulmonary vascular congestion that frequently occurs with exertion. Interatrial shunts represent a novel treatment modality for HFpEF. These shunts allow for left atrial decongestion and a reduction in pulmonary venous hypertension during exercise leading to improvements in hemodynamics, functional status and quality of life. Trials to date have demonstrated safety and short-term efficacy of these devices for HFpEF. The long-term benefits are currently being evaluated in ongoing trials. If effective, the use of interatrial shunts may be a new therapeutic paradigm for the treatment of HFpEF.

Diastolic Heart Failure: A Review of Current and Future Treatment Options.

Heart failure with preserved ejection fraction (HFpEF), often referred to as diastolic heart failure, remains one of the more challenging forms of heart failure to treat. This is a condition in which patients may or may not have signs and symptoms of heart failure, and retain a left ventricular ejection fraction greater than 50%. The challenge to treating HFpEF is due to the paucity of clinical trials with specific therapies, and those that have been completed have yielded relatively neutral results. This has resulted in treatments that are aimed more towards associated conditions, such as hypertension, rather than the underlying pathophysiology. This article will review the epidemiology and pathophysiology of HFpEF, and discuss the current therapeutic modalities, and clinical trials. In addition, we will discuss an ongoing clinical trial and the impact it may hold on future treatment options.

Heart failure with preserved ejection fraction: insights into diagnosis and pathophysiology.

Heart failure with preserved ejection fraction (HFpEF) accounts for at least half the cases of heart failure, currently diagnosed. There are several cardiac and non-cardiac manifestations of the syndrome. Structure and function abnormalities can include all four cardiac chambers. The left ventricle has abnormal systolic and diastolic functions which can be examined by invasive and non-invasive measurements. In addition, the left atrium enlarges with abnormal left atrial function, pulmonary hypertension occurs, and the right ventricle can develop hypertrophy, enlargement, and systolic dysfunction. There are a paucity of data on calcium handling in HFpEF patients. Growing literature supports the presence of abnormalities in titin and its phosphorylation, and increased interstitial fibrosis contributing to increased chamber stiffness. A systemic inflammatory state causing reduced myocardial cyclic guanosine monophosphate along with defects in the unfolded protein response have been recently reported. Diagnosis relies on signs and symptoms of heart failure, preserved ejection fraction, and detection of diastolic function abnormalities based on echocardiographic findings and abnormally elevated natriuretic peptide levels or invasive measurements of wedge pressure at rest or with exercise. There are currently two diagnostic algorithms: H2FPEF, and HFA-PEFF with limited data comparing their performance head to head in the same patient population. Despite the growing understanding of the syndrome's pathophysiology, there have been little success in developing specific treatment for patients with HFpEF.

Impact of Sirolimus as a Primary Immunosuppressant on Myocardial Fibrosis and Diastolic Function Following Heart Transplantation.

Background Myocardial fibrosis is an important contributor for development of diastolic dysfunction. We investigated the impact of sirolimus as primary immunosuppression on diastolic dysfunction and fibrosis progression among heart transplantation recipients. Methods and Results In 100 heart transplantation recipients who were either treated with a calcineurin inhibitor (CNI) (n=51) or converted from CNI to sirolimus (n=49), diastolic function parameters were assessed using serial echocardiograms and right heart catheterizations. Myocardial fibrosis was quantified on serial myocardial biopsies. After 3 years, lateral e' increased within the sirolimus group but decreased in the CNI group (0.02±0.04 versus -0.02±0.04 m/s delta change; P=0.003, respectively). Both pulmonary capillary wedge pressure and diastolic pulmonary artery pressure significantly decreased in the sirolimus group but remained unchanged in the CNI group (-1.50±2.59 versus 0.20±2.20 mm Hg/year; P=0.02; and -1.72±3.39 versus 0.82±2.59 mm Hg/year; P=0.005, respectively). A trend for increased percentage of fibrosis was seen in the sirolimus group (8.48±3.17 to 10.10±3.0%; P=0.07) as compared with marginally significant progression in the CNI group (8.76±3.87 to 10.56±4.34%; P=0.04). The percent change in fibrosis did not differ significantly between the groups (1.62±4.67 versus 1.80±5.31%, respectively; P=0.88). Conclusions Early conversion to sirolimus is associated with improvement in diastolic dysfunction and filling pressures as compared with CNI therapy. Whether this could be attributed to attenuation of myocardial fibrosis progression with sirolimus treatment warrants further investigation.

Use of Inflammatory Biomarkers and Real-Time Cardiac Catheterisation to Evaluate the Left Ventricular Diastolic Function in Patients With Diastolic Heart Failure.

BACKGROUND: Interleukin (IL)-17 and its related cytokines have been shown to be involved in myocardial fibrosis and irreversible ventricular remodelling, which have predictive values in the development of left ventricular diastolic dysfunction (LVDD). This study aimed to assess the correlation between IL-17 and LVDD, and investigate the prognostic value of IL-17 among patients with normal left ventricular ejection fraction (LVEF). METHODS: A total of 120 patients with normal LVEF underwent left ventricular (LV) catheterisation for LV end-diastolic pressure (LVEDP) measurement and routine echocardiography. The follow-up period was 30 (18, 35) months. RESULTS: The levels of IL-17 and IL-6 from the systemic blood were significantly increased in non-heart failure (HF) patients with LVDD (p<0.001). Receiver operating characteristic (ROC) revealed that the combination of IL-17 and IL-6 showed the highest diagnostic accuracy in predicting LVDD (AUC, 0.890; 95% CI, 0.835-0.945; p<0.001), and the cut-off value was 41.5 pg/mL. On logistic regression analysis, the increment of the combination of IL-17 and IL-6 was an independent predictor for the prognosis of LVDD (odds ratio, 1.25; 95% CI, 1.01-1.12; p<0.05). According to the cut-off value of the combination of IL-17 and IL-6, the patients with lower levels of IL-17 and IL-6 (<41.5 pg/mL group) had a better prognosis. The increased levels of IL17 and IL-6 were significantly correlated with the levels of fibrotic parameters. CONCLUSIONS: Assessment of LVDD by measuring the combination of IL-17 and IL-6 might provide valuable prognostic significance for non-HF patients with LVDD.

Diastolic Function and Clinical Outcomes After Transcatheter Aortic Valve Replacement: PARTNER 2 SAPIEN 3 Registry.

BACKGROUND: Few studies have evaluated if diastolic function could predict outcomes in patients with aortic stenosis. OBJECTIVES: The authors aimed to assess the association between diastolic dysfunction (DD) and outcomes in patients with aortic stenosis undergoing transcatheter aortic valve replacement (TAVR). METHODS: Baseline, 30-day, and 1- and 2-year transthoracic echocardiograms from the PARTNER (Placement of Aortic Transcatheter Valves) 2 SAPIEN 3 registry were analyzed by a consortium of core laboratories and divided into the American Society of Echocardiography DD groups. RESULTS: Among the 1,750 included, 682 (54.4%) had grade 1 DD, 352 (28.1%) had grade 2 DD, 168 (13.4%) had grade 3 DD, and 51 (4.1%) had indeterminate DD grade. Incremental baseline grades of DD were associated with an increase in combined 1- and 2-year cardiovascular (CV) death/rehospitalization (all p < 0.002) and all-cause death at 2 years (p = 0.01) but not at 1 year. Improvement in DD grade/grade 1 DD at 30 days post-TAVR was seen in 70.8% patients. Patients with improvement in ≥1 grade of DD/grade 1 DD had reduced 1-year CV death/rehospitalization (p < 0.001) and increased 2-year survival (p = 0.01). Baseline grade 3 DD was a predictor of 1-year CV death/rehospitalization (hazard ratio: 2.73; 95% confidence interval: 1.07 to 6.98; p = 0.04). Improvement in DD grade/grade 1 DD at 30 days was protective for 1-year CV death/rehospitalizations (hazard ratio: 0.39; 95% confidence interval: 0.19 to 0.83; p = 0.01). CONCLUSIONS: In the PARTNER 2 SAPIEN 3 registry, baseline DD was a predictor of up to 2 years clinical outcomes in patients who underwent TAVR. Improvement in DD grade at 30 days was associated with improvement in short-term clinical outcomes. (The PARTNER II Trial: Placement of AoRTic TraNscathetER Valves II - PARTNER II - PARTNERII - S3 Intermediate [PARTNERII S3i]; NCT03222128; PARTNER II Trial: Placement of AoRTic TraNscathetER Valves II - High Risk and Nested Registry 7 [PII S3HR/NR7]; NCT03222141).