Management of Pulmonary Hypertension in the Context of Heart Failure with Preserved Ejection Fraction.

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. 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.

Heart failure with preserved ejection fraction: relevance of a dedicated dyspnoea clinic.

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.

Comorbidities, pharmacologic interventions, and mechanical interventions associated with mortality in isolated diastolic left heart failure: lessons from a national database.

BACKGROUND: Diastolic heart failure may be noted in paediatric patients with CHD, cardiomyopathy, or malignancies requiring chemotherapy, but the available data are scarce, and often derived from adult trials or based on theoretic or anecdotal evidence. METHODS: Data between 2016 and 2021 were obtained from Pediatric Health Information System database. Patients <18 years of age with isolated diastolic heart failure admitted to ICU at some point during admission were included. They were divided into patients with and without inpatient mortality. Patients' demographics, comorbidities using ICD-10 codes, and pharmacologic interventions were also recorded. Univariate analysis was done in demographics, comorbidities, pharmacologic interventions, and mechanical interventions between admissions with and without mortality. Multivariable logistic regression was done for inpatient mortality and multivariable linear regression was done for total hospital length of stay in survivors. RESULTS: Isolated diastolic heart failure comprised 0.5% of critically ill paediatric patients. A total of 121 (5%) experienced mortality among the 2,273 admissions in the final analyses. Milrinone and angiotensin converting enzyme inhibitor were found to be associated with decreased mortality. Increasing age and diuretics were associated with decreased total hospital length of stay in survivors. CONCLUSION: In the cohort studied, isolated diastolic left heart failure has a 5% mortality. Several comorbidities and interventions are associated with increased mortality with milrinone and angiotensin converting enzyme inhibitors being associated with decreased risk of mortality. When only admissions with survival to discharge are considered, older age and diuretics are associated with lower total hospital length of stay.

[Clinical case of generalized amyloidosis (ATTR-amyloidosis) with a progressive course of chronic heart failure. Case report].

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.

Heart Failure with Preserved Ejection Fraction in Children.

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.

Heart failure with preserved ejection fraction in patients with normal natriuretic peptide levels is associated with increased morbidity and mortality.

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.

Sacubitril/Valsartan Cannot Improve Cardiac Function Compared with Valsartan in Patients Suffering Nonvalvular Atrial Fibrillation without Systolic Heart Failure.

This study investigates the effect of sacubitril/valsartan (Sac/Val) in patients diagnosed with nonvalvular atrial fibrillation (AF) without systolic heart failure (SHF).Nonvalvular AF patients without SHF admitted to the People's Hospital of Bortala Mongol Autonomous Prefecture from December 2020 to December 2021 were enrolled and randomly divided into Sac/Val treatment group (group T) and valsartan treatment group (group C, control). For subgroup analysis, patients were divided into subgroups with and without diastolic heart failure (DHF). After 1-month adaptive phase and subsequent 3-month treatment period, patients were followed up in the cardiology clinic. Plasma levels of biochemical markers and echocardiographic parameters before and after treatment were evaluated, and DHF scores were computed to assess diastolic function.Of 61 enrolled patients, 46 patients completed follow-up. Sac/Val treatment did not increase the percentage of sinus rhythm. Although N-terminal pro-B-type natriuretic peptide (NT-proBNP) expression tended to be reduced in both groups after 3 months of treatment, the differences compared with respective baseline levels and between groups were not significant. According to subgroup analysis, although NT-proBNP expression in the subgroup with DHF was lower at follow-up compared to baseline, the difference was not statistically significant. Similarly, no marked differences in echocardiographic parameters or tissue Doppler parameters related to DHF were detected between the groups (P > 0.05). Additionally, a subgroup analysis found no significant variations in the echocardiographic measures (P > 0.05).Sac/Val is not superior to valsartan for the short-term treatment of patients suffering with AF without SHF in improving NT-proBNP level and cardiac function.

Heart failure with a preserved ejection fraction and the EMPEROR-Preserved Trial: a review of how we got here.

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.

Large animal models of heart failure with preserved ejection fraction.

Heart failure with preserved ejection fraction (HFpEF) is characterized by diastolic dysfunction and multiple comorbidities. The number of patients is continuously increasing, with no improvement in its unfavorable prognosis, and there is a strong need for novel treatments. New devices and drugs are difficult to assess at the translational preclinical step due to the lack of high-fidelity large animal models of HFpEF. In this review, we describe the summary of historical and evolving techniques for developing large animal models. The representative methods are pressure overload models, including (1) aortic banding, (2) aortic stent, (3) renal hypertension, and (4) mineralocorticoid-induced hypertension. Diet-induced metabolic syndromes are also used. A new technique with an inflatable balloon inside the left ventricle can be used during acute/chronic in vivo surgeries to simulate HFpEF-like hemodynamics for pump-based therapies. Canines and porcine are most widely used, but other non-rodent animals (sheep, non-human primates, felines, or calves) have been used. Feline models present the most well-simulated HFpEF pathology, but small size is a concern, and the information is still very limited. The rapid and reliable establishment of large animal models for HFpEF, and novel methodology based on the past experimental attempts with large animals, are needed.

Treatment of heart failure with preserved ejection fraction with SGLT2 inhibitors: new therapy standard?

Heart failure with preserved ejection fraction (HFpEF) is a common and difficult-to-treat heart disease. Approximately half of patients with heart failure suffer from this form, and mortality is between 5% and 7% per year. Previous therapeutic trials for the treatment of HFpEF have been disappointing. However, recent data on therapy with sodium-glucose cotransporter­2 (SGLT2) inhibitors in HFpEF are encouraging. In addition to numerous experimental studies showing improvement in diastolic dysfunction parameters, the EMPEROR-Preserved study demonstrated for the first time clinically that therapy with the SGLT2 inhibitor empagliflozin significantly reduced hospitalization for heart failure. By contrast, cardiovascular mortality was not affected. Differences for patients with and without type 2 diabetes mellitus were not observed. Thus, for the first time, there is an evidence-based treatment option to reduce hospitalization and improve quality of life in these patients. Further studies will show to what extent these beneficial effects will also lead to an improvement in the prognosis of these patients.

Early Identification of Patients at Risk for Incident Heart Failure With Preserved Ejection Fraction: Novel Approach to Echocardiographic Trends.

BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) continues to increase in prevalence with a 50% mortality rate within 3 years of diagnosis, but lacking effective evidence-based therapies. Specific echocardiographic markers are not typically used to trigger alarm before acute HFpEF decompensation. The goal of this study was to retrospectively track changes in echocardiographic markers leading to the time of incident HFpEF hospitalization. METHODS AND RESULTS: In a single-center, retrospective analysis, patients with HFpEF admitted between 2007 and 2014 were identified using the International Classification of Diseases, 9th Revision with search refined using the European Society of Cardiology HFpEF guidelines. Using linear mixed effects models, changes in echocardiographic markers preceding acute HF decompensation owing to incident HFpEF were analyzed. We report on an incident HFpEF cohort of 242 patients, extending 18 years retrospectively, and including 675 echocardiograms analyzed from the overall sample at 14 distinct time intervals before acute decompensation. The regression models demonstrated 3 echocardiographic markers with statistically significant increases across multiple time intervals including, arterial elastance (P = .006), right atrial pressure estimate (P < .001), and right ventricular systolic pressure (P = .006). Other echocardiographic markers had individual time intervals with significant increases before acute decompensation, including (a) left atrial diameter, 8 to 10 years before HFpEF diagnosis, (b) left ventricular filling pressure 2 to 6 years before HFpEF diagnosis, (c) ventricular elastance 3 to 6 months before HFpEF diagnosis, and (d) ventricular elastance/arterial elastance as early as 10 to 20 years and as late as 3 to 6 months before HFpEF diagnosis. Furthermore, African Americans presented with incident HFpEF at an average younger age than White patients (65.6 ± 15.2 years vs. 76.7 years ± 11.7, P < .001). CONCLUSIONS: Noninvasive echocardiographic markers associated with incident HFpEF diagnosis showed long, mid, and acute range, significant changes as far back as 10 to 20 years and as close as 3 to 6 months before acute HFpEF decompensation. Including a diverse study cohort is critical to understanding the phenotypic differences of HFpEF. This hypothesis-generating study identified a novel approach to identifying trends in echocardiographic markers that may be used as a signal of impending incident HFpEF.

Diagnostic and prognostic value of serum C-reactive protein in heart failure with preserved ejection fraction: a systematic review and meta-analysis.

Heart failure (HF) is a major epidemic with rising morbidity and mortality rates that encumber global healthcare systems. While some studies have demonstrated the value of CRP in predicting (i) the development of HFpEF and (ii) long-term clinical outcomes in HFpEF patients, others have shown no such correlation. As a result, we conducted the following systematic review and meta-analysis to assess both the diagnostic and prognostic role of CRP in HFpEF. PubMed and Embase were searched for studies that assess the relationship between CRP and HFpEF using the following search terms: (((C-reactive protein) AND ((preserved ejection fraction) OR (diastolic heart failure))). The search period was from the start of database to August 6, 2019, with no language restrictions. A total of 312 and 233 studies were obtained from PubMed and Embase respectively, from which 19 studies were included. Our meta-analysis demonstrated the value of a high CRP in predicting the development of not only new onset HFpEF (HR: 1.08; 95% CI: 1.00-1.16; P = 0.04; I2 = 22%), but also an increased risk of cardiovascular mortality when used as a categorical (HR: 2.52; 95% CI: 1.61-3.96; P < 0.0001; I2 = 19%) or a continuous variable (HR: 1.24; 95% CI: 1.04-1.47; P = 0.01; I2 = 28%), as well as all-cause mortality when used as a categorical (HR: 1.78; 95% CI: 1.53-2.06; P < 0.00001; I2 = 0%) or a continuous variable: (HR: 1.06; 95% CI: 1.02-1.06; P = 0.003; I2 = 61%) in HFpEF patients. CRP can be used as a biomarker to predict the development of HFpEF and long-term clinical outcomes in HFpEF patients, in turn justifying its use as a simple, accessible parameter to guide clinical management in this patient population. However, more prospective studies are still required to not only explore the utility and dynamicity of CRP in HFpEF but also to determine whether risk stratification algorithms incorporating CRP actually provide a material benefit in improving patient prognosis.

Device-based treatment options for heart failure with preserved ejection fraction.

Heart failure with preserved ejection fraction (HFpEF) is a syndrome with an unfavorable prognosis, and the number of the patients continues to grow. Because there is no effective therapy established as a standard, including pharmacological treatments, a movement to develop and evaluate device-based therapies is an important emerging area in the treatment of HFpEF patients. Many devices have set their target to reduce the left atrial pressure or pulmonary capillary wedge pressure because they are strongly related to the symptoms and prognosis of HFpEF, but the methodology to achieve it varies based on the devices. In this review, we summarize and categorize these devices into the following: (1) interatrial shunt devices, (2) left ventricle expander, (3) electrical therapy, (4) left ventricular assist devices, and (5) mechanical circulatory support devices under development. Here, we describe the features and specifications of device-based therapies currently under development and those at more advanced stages of preclinical testing. Advantages and limitations of these technologies, with insights on their safety and feasibility for HFpEF patients, are described.

Comparing outcomes of diabetic ketoacidosis hospitalisations in patients with diastolic heart failure: A retrospective propensity matched analysis of the nationwide inpatient sample.

INTRODUCTION: Diabetic ketoacidosis (DKA) is a known complication of patients with diabetes mellitus. The aim of this study was to compare the outcomes of patients admitted with a diagnosis of DKA with, and without, diastolic heart failure (DHF). METHODS: This was a population-based, retrospective, observational study using data from the National Inpatient Sample database for the years 2016 and 2017. The primary outcome was in-hospital mortality. Secondary outcomes were rates of sepsis, non-ST elevation myocardial infarctions (NSTEMI), acute kidney failure, acute respiratory failure (ARF), deep vein thrombosis, pulmonary embolism, mean length of hospital stay (LOS) and total hospital charges (THC). RESULTS: There was no statistically significant difference for the adjusted odds for in-hospital mortality between patients with and without DHF (adjusted odds ratio [aOR]: 0.55, 95% confidence interval [CI] 0.28-1.08, p = 0.081). Patients with DKA and DHF had increased odds of developing an NSTEMI (aOR: 1.31, 95% CI: 1.01-1.70, p = 0.045) or ARF (aOR: 1.82, 95% CI: 1.38-2.40, p < 0.001) during the same admission compared to patients without DHF. Patients with DKA and DHF also had an increased mean THC (6500 CI: 1900-11,200, p = 0.0006) in US dollars and increased LOS (0.7, 95% CI: 0.2-1.3, p = 0.011) in days when compared to patients without DHF. CONCLUSIONS: Patients with DKA showed no statistically significant difference in mortality if they did or did not have a secondary diagnosis of DHF within the same admission.

Constrictive pericarditis in the setting of repeated chest trauma in a mixed martial arts fighter.

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.

Relationship between paced QRS duration and myocardial relaxation of the left ventricle in patients with chronic right ventricular apical pacing.

BACKGROUND: Right ventricular (RV) apical pacing is associated with systolic dysfunction and heart failure. Paced QRS duration has been suggested as a predictor of heart failure and left ventricular (LV) systolic dysfunction. However, the effect of paced QRS duration on LV diastolic function is not well known. OBJECTIVE: This study was designed to evaluate the relationship between paced QRS duration and LV diastolic function. METHODS: This retrospective study included 88 patients who had chronic RV apical pacing. Myocardial relaxation was assessed with tissue Doppler imaging. Patients with severe valvular dysfunction or significant structural heart disease were excluded. Paced QRS duration was measured with standard 12­lead ECG at follow-up. RESULTS: Median age of the patients was 65.9 years (interquartile ranges (IQR), 56.5, 72.7) with 64.8% of female patients. Median duration of RV pacing was 8.6 years (IQR, 5.3, 11.1). Major indication of RV pacing was complete atrioventricular block (89.8%), and dual chamber pacemakers were predominantly implanted (89.8%). Mean of paced QRS duration was 160.5 ± 18.2 msec. Median LV ejection fraction (EF) was 63% (IQR, 55.5, 67.5), and negatively correlated with paced QRS duration (R = -0.478, p < 0.001). LV end diastolic dimension was positively correlated with paced QRS duration (R = 0.531, p < 0.001). Mean E' velocity at the septal mitral annulus was 5.2 ± 1.5 and negatively related to paced QRS duration (R = -0.521, p < 0.001). After adjusting covariables, paced QRS duration was independently related to E' velocity (beta = -0.038, p = 0.005). Paced QRS duration was also associated with worsening functional capacity or elevated LV filling pressure in patients with preserved EF (odd ratio = 1.10; 95% confidence interval, 1.02-1.20, p = 0.015). CONCLUSION: Paced QRS duration was associated with LV relaxation which might be another possible mechanism of worsening heart failure in patients with long paced QRS duration.

Heart Failure with Preserved Ejection Fraction.

Heart failure (HF) is a clinical syndrome of diverse etiologies and can be associated with preserved, reduced, or mid-range ejection fraction (EF). In the community, heart failure with preserved ejection fraction (HFpEF) is emerging as the most common form of HF. There remains considerable uncertainty regarding its pathogenesis, diagnosis, and optimal therapeutic approach. Hypotheses have been advanced to explain the underlying pathophysiology responsible for HFpEF, but to date, no specific therapy based on these hypotheses has been proven to improve outcomes in HFpEF. We provide a clinically focused review of the epidemiology, clinical presentation, diagnostic approach, pathophysiology, and treatment of HFpEF.

Diagnostic value of novel biomarkers for heart failure : A meta-analysis.

BACKGROUND: The present meta-analysis examined the diagnostic value of novel biomarkers for heart failure (HF), including copeptin, galectin-3, hs-cTnT, MR-proANP, MR-proADM, and ST2. METHODS: English (EMBASE, Cochrane, and PubMed) and Chinese (Wanfang data, CNKI, SinoMed) databases were searched to identify suitable studies that were published before 1 December 2016. Data were extracted using standard forms. Pooled diagnostic statistics were calculated using DerSimonian-Laird random-effects models. RESULTS: The analysis comprised 45 studies. The pooled sensitivities of all biomarkers were 0.80-0.86, along with pooled specificities of 0.60-0.82, positive predictive values (PPVs) of 0.52-0.80, and negative predictive values (NPVs) of 0.70-0.87. Among them, hs-cTnT had the highest sensitivity (0.86 [95% CI: 0.84-0.88]), specificity (0.82 [95% CI: 0.79-0.84]), PPV (0.80 [95% CI: 0.77-0.83]), and NPV (0.87 [95% CI: 0.85-0.89]), while MR-proADM had the lowest sensitivity (0.80 [95% CI: 0.75-0.84]), specificity (0.60 [95% CI: 0.56-0.64]), and PPV (0.52 [95% CI: 0.47-0.56]). Copeptin had the lowest NPV (0.70 [95% CI: 0.66-0.74]). The positive likelihood ratio (LR+) of all biomarkers ranged from 1.97 to 3.21, and the negative likelihood ratio (LR-) from 0.20 to 0.36. MR-proADM had the lowest LR+ and highest LR-; galectin-3 had the highest LR+ and MR-proANP had the lowest LR-. The area under the curve (AUC) was as low as 0.68 for MR-proADM, while AUCs for the other biomarkers ranged from 0.83 to 0.89. CONCLUSION: The overall diagnostic accuracy of copeptin, galectin-3, hs-cTnT, MR-proANP, and ST2 was relatively good. MR-proADM had a poor capacity to confirm or exclude HF. Improving the diagnostic accuracy of HF by a combination of biomarkers could be considered in the future.

T Cells Play a Causal Role in Diastolic Dysfunction during Uremic Cardiomyopathy.

BACKGROUND: Uremic cardiomyopathy, characterized by left ventricular hypertrophy, diastolic dysfunction, and impaired myocardial strain, contributes to increased cardiovascular mortality in patients with CKD. Emerging evidence suggests a pathogenic role for T cells during chronic heart failure. METHODS: To determine whether T cells contribute to uremic cardiomyopathy pathogenesis, we modeled this condition by inducing CKD via 5/6th nephrectomy in mice. We used flow cytometry to assess expression of markers of T cell memory or activation by lymphocytes from CKD mice and controls, as well as lymphocyte capacity for cytokine production. Flow cytometry was also used to quantify immune cells isolated from heart tissue. To test effects of T cell depletion on cardiac function, we gave CKD mice anti-CD3 antibody injections to deplete T cells and compared heart function (assessed by echocardiography) with that of controls. Finally, we correlated T cell phenotypes with structural and functional measures on clinically acquired echocardiograms in children with CKD. RESULTS: Mice with CKD accumulated T cells bearing markers of memory differentiation (CD44hi) and activation (PD-1, KLRG1, OX40), as reported previously in human CKD. In addition, mice with CKD showed T cells infiltrating the heart. T cell depletion significantly improved both diastolic function and myocardial strain in CKD mice without altering hypertension or degree of renal dysfunction. In children with CKD, increasing frequency of T cells bearing activation markers PD-1 and/or CD57 was associated with worsening diastolic function on echocardiogram. CONCLUSIONS: CKD results in an accumulation of proinflammatory T cells that appears to contribute to myocardial dysfunction.

The Heart Failure with Preserved Ejection Fraction Conundrum-Redefining the Problem and Finding Common Ground?

PURPOSE OF REVIEW: Heart failure with preserved ejection fraction (HFpEF) or diastolic heart failure (DHF) makes up more than half of all congestive heart failure presentations (CHF). With an ageing population, the case load and the financial burden is projected to increase, even to epidemic proportions. CHF hospitalizations add too much of the financial and infrastructure strain. Unlike systolic heart failure (SHF), much is still either uncertain or unknown. Specifically, in epidemiology, the disease burden is established; however, risk factors and pathophysiological associations are less clear; diagnostic tools are based on rigid parameters without the ability to accurately monitor treatments effects and disease progression; finally, therapeutics are similar to SHF but without prognostic data for efficacy. RECENT FINDINGS: The last several years have seen guidelines changing to account for greater epidemiological observations. Most of these remain general observation of shortness of breath symptom matched to static echocardiographic parameters. The introduction of exercise diastolic stress test has been welcome and warrants greater focus. HFpEF is likely to see new thinking in the coming decades. This review provides some of perspective on this topic.