Association of Pan Immune-Inflammation Value with Long Term Outcomes of Acute Decompensated Heart Failure. / Associação do Valor Pan-Imune-Inflamatório com Desfechos de Longo Prazo na Insuficiência Cardíaca Agudamente Descompensada.

BACKGROUND: Although there have been significant improvements in the treatment of heart failure (HF) in recent decades, its prognosis remains poor. Although there are many biomarkers that can help predict the prognosis of patients with HF, there is a need for simpler, cheaper, and more easily available biomarkers. OBJECTIVE: To evaluate the predictive value of pan-immune-inflammation value (PIV) in patients with acute decompensated HF. METHODS: We analyzed 409 patients with HF with reduced ejection fraction who were hospitalized for acute decompensated HF. Patients were divided into 3 groups according to tertiles of PIV: tertile 1 (PIV < 357.25), tertile 2 (PIV ≥ 357.25 and < 834.55), and tertile 3 (PIV ≥ 834.55). P values < 0.05 were considered statistically significant. Kaplan-Meier curves and Cox proportional hazards regression models were used to evaluate the association between PIV and all-cause mortality. The primary outcome was 5-year all-cause mortality, and the secondary outcomes were in-hospital 30 days,, 180-day, and 1-year all-cause mortality. RESULTS: We showed that higher PIV value was associated with both primary and secondary outcomes. The Kaplan-Meier curve showed that patients with higher PIV values had an increased risk of short- and long-term all-cause mortality (log-rank p < 0.001). In the multivariate analysis, PIV was identified as an independent predictor of long-term all-cause mortality in patients with acute decompensated HF, and we observed a 1.96-fold increase in the hazard of an event (odds ratio: 1.96, 95% confidence interval: 1.330 to 2.908, p = 0.001). CONCLUSIONS: Our study showed that the novel biomarker PIV can be used as a predictor of prognosis in patients with acute decompensated HF.

FUNDAMENTO: Embora tenha havido melhorias significativas no tratamento da insuficiência cardíaca (IC) nas últimas décadas, seu prognóstico permanece desfavorável. Embora existam muitos biomarcadores que podem ajudar a prever o prognóstico de pacientes com IC, há necessidade de biomarcadores mais simples, menos dispendiosos e mais facilmente disponíveis. OBJETIVO: Avaliar o valor preditivo do valor pan-imune-inflamatório (PIV, do inglês pan-immune-inflammation value) em pacientes com IC agudamente descompensada. MÉTODOS: Analisamos 409 pacientes com IC com fração de ejeção reduzida internados por IC aguda descompensada. Os pacientes foram divididos em 3 grupos de acordo com os tercis de PIV: tercil 1 (PIV < 357,25), tercil 2 (PIV ≥ 357,25 e < 834,55) e tercil 3 (PIV ≥ 834,55). Foram considerados estatisticamente significativos valores de p < 0,05. Curvas de Kaplan-Meier e modelos de regressão de riscos proporcionais de Cox foram utilizados para avaliar a associação entre PIV e mortalidade por todas as causas. O desfecho primário foi mortalidade por todas as causas em 5 anos, e o desfecho secundário compreendeu a mortalidade por todas as causas intra-hospitalar em 30 dias, em 180 dias e em 1 ano. RESULTADOS: Mostramos que valores mais elevados de PIV estavam associados a desfechos primários e secundários. A curva de Kaplan-Meier mostrou que pacientes com valores mais elevados de PIV apresentaram risco aumentado de mortalidade por todas as causas em curto e longo prazo (log-rank p < 0,001). Na análise multivariada, o PIV foi identificado como um preditor independente de mortalidade por todas as causas em longo prazo em pacientes com IC aguda descompensada, e observamos um aumento de 1,96 vezes no risco de um evento (razão de chances: 1,96; intervalo de confiança de 95%: 1,330 a 2,908; p = 0,001). CONCLUSÕES: Nosso estudo mostrou que o novo biomarcador PIV pode ser usado como preditor de prognóstico em pacientes com IC aguda descompensada.

The Most Predictive Red Flags for Suspecting Cardiac Amyloidosis in Patients with Heart Failure with Preserved Ejection Fraction.

OBJECTIVE: Cardiac amyloidosis (CA) is a cardiomyopathy characterized by amyloid infiltration in the myocardium. Transthyretin cardiac amyloidosis (TTR-CA), commonly presenting as heart failure with preserved ejection fraction (HFpEF), was the focus of our study, which aimed to identify red flags that heighten suspicion of CA in HFpEF patients. METHODS: We prospectively included patients diagnosed with HFpEF. All patients were assessed for TTR-CA red flag features, cardiac and extra-cardiac, as outlined in the 'Diagnosis and Treatment of Cardiac Amyloidosis: A Position Statement of the European Society of Cardiology.' Technetium-99m pyrophosphate (99mTc-PYP) cardiac scintigraphy was performed in 167 HFpEF patients suspected of having TTR-CA. Patients testing positive and negative for TTR-CA were compared based on these red flag features. RESULTS: Out of 167 HFpEF patients, 19 (11.3%) were diagnosed with TTR-CA. In the TTR-CA group, 17 (89.5%) patients were 65 years or older. The presence of three or more red flags differentiated the TTR-CA positive and negative groups (P = 0.040). Features such as low voltage and pseudo infarct patterns were more prevalent in the TTR-CA group (P < 0.001 and P < 0.048, respectively). Left ventricular global longitudinal strain (LV-GLS) was lower in the TTR-CA positive group (P < 0.001). Multivariate analysis identified four variables-older age, pseudo infarct pattern, low/decreased QRS voltage, and LV-GLS-as strong, independent predictors of TTR-CA, with significant odds ratios (ORs) of 7.8, 6.8, 16.9, and 1.2, respectively. CONCLUSION: In this study, TTR-CA etiology occurs in approximately one in every ten HFpEF patients. The presence of three or more red flags increases the likelihood of TTR-CA. Older age, pseudo infarct pattern, low/decreased QRS voltage, and reduced LV-GLS are the most significant red flags indicating TTR-CA in HFpEF patients.

Current barriers and recommendations on the diagnosis of transthyretin amyloid cardiomyopathy: a Delphi study.

Objectives: This study has been conducted to investigate the non-invasive diagnostic journey of patients with a transthyretin amyloid cardiomyopathy (aTTR-CM) in Turkey, identify the challenges and uncertainties encountered on the path to diagnosis from the perspectives of expert physicians, and develop recommendations that can be applied in such cases. Methods: This study employed a three-round modified Delphi method and included 10 cardiologists and five nuclear medicine specialists. Two hematologists also shared their expert opinions on the survey results related to hematological tests during a final face-to-face discussion. A consensus was reached when 80% or more of the panel members marked the "agree/strongly agree" or "disagree/strongly disagree" option. Results: The panelists unanimously agreed that the aTTR-CM diagnosis could be established through scintigraphy (using either 99mTc-PYP, 99mTc-DPD, or 99mTc-HMPD) in a patient with suspected cardiac amyloidosis (CA) without a further investigation if AL amyloidosis is ruled out (by sFLC, SPIE and UPIE). In addition, scintigraphy imaging performed by SPECT or SPECT-CT should reveal a myocardial uptake of Grade ≥2 with a heart-to-contralateral (H/CL) ratio of ≥1.5. The cardiology panelists recommended using cardiovascular magnetic resonance (CMR) and a detailed echocardiographic scoring as a last resort before considering an endomyocardial biopsy in patients with suspected CA whose scintigraphy results were discordant/inconclusive or negative but still carried a high clinical suspicion of aTTR-CM. Conclusion: The diagnostic approach for aTTR-CM should be customized based on the availability of diagnostic tools/methods in each expert clinic to achieve a timely and definitive diagnosis.

Different Cardio-Selective ß-Blockers and the Prevention of Exaggerated Blood Pressure Response During Exercise: A Retrospective Cross-Sectional Study.

OBJECTIVE: The aim of this study was to analyze the role of various ß-blockers in managing exercise-induced blood pressure escalations, referred to as exaggerated blood pressure response (eBPR). Despite the importance of this phenomenon, there is limited data on the efficacy of ß-blockers in controlling eBPR. METHOD: Our retrospective cohort for this study comprised 2,803 individuals who underwent treadmill tests from January 2016 to February 2018. A further subgroup analysis of 1,258 patients receiving ß-blocker treatment was performed to evaluate the influence of different ß-blockers on eBPR. RESULTS: The results demonstrated that ß-blockers play a significant role in mitigating the occurrence of eBPR (P = 0.026), irrespective of the specific type of ß-blocker. Additionally, no significant variance was observed in the development of eBPR among the different ß-blocker groups (P = 0.532 for systolic blood pressure (BP); P = 0.068 for diastolic BP). This finding remained consistent even among the 992 hypertensive patients, where no notable association was found between the type of ß-blocker and the development of eBPR (P = 0.736 for systolic BP; P = 0.349 for diastolic BP). It is noteworthy that patients using ß-blockers had unique clinical and demographic attributes. CONCLUSION: Our study suggests that ß-blockers can potentially deter the development of eBPR during physical activity, a benefit that is consistent across all types of ß-blockers. The study sheds light on prospective randomized studies on the use of eBPR as a new treatment target.

Patient Perception, Knowledge and Adaptation in The Management of Heart Failure: A Multicenter, Cross-Sectional, Observational, Questionnaire-Based Study: ADAPTATION HF.

OBJECTIVE: The aim of this study is to reveal the perception levels of heart failure (HF) patients about the disease, their adaptation to the disease process, their compliance with the treatment, and their knowledge and thoughts about the disease from the patient's perspective. METHOD: Patients with a diagnosis of HF for at least 6 months who applied to the cardiology clinics of 10 different centers were included in this cross-sectional, multicenter and questionnaire-based study. A questionnaire consisting of sections that included demographic information, evaluation of the patient's symptoms, knowledge and experience of clinical follow-up, knowledge of HF, compliance and awareness of treatment was applied to the patients. RESULTS: 504 patients with a mean age of 59.8 ± 14.9 years (M/F: 360/144, 71.4%/28.6%) were included in the study. 61.2% of the patients stated that they knew about HF disease before. Most of the patients knew that the complaints of shortness of breath, fatigue and palpitation could develop due to HF (95.4%; 92.7%; 89.7%, respectively). The patients reported that they were mostly worried about not being able to provide their own self-care without the support of another person (67.5%). While the majority of patients (37.6%) thought that the worst disease was to have a cerebrovascular disease; only 10.9% stated that HF was the worst disease. While 98.8% of the patients stated that they used HF drugs regularly, a relatively large part of the patients did not know that the drugs were effective on kidney functions (68.5%) and blood pressure (76.9%). In the daily practice of the patients, the rate of weight follow-up was 35.5%, the rate of blood pressure monitoring was 26.9%, and the rate of patients who exercised was 27%. Among the patients, 73.3% said that they pay attention to the amount of salt they take with diet, and 33.5% have a completely salt.free diet. There was no difference between the groups with low and high knowledge scores in terms of Pittsburgh Sleep Quality Index (P > 0.005). The knowledge level score was significantly higher in patients with previous myocardial infarction (P = 0.002). CONCLUSION: Most of the HF patients participating in the study are aware of the signs and symptoms of HF, follow the recommendations of their physicians, and use drugs regularly. These patients should have more information about blood pressure monitoring, weight monitoring, diet and sodium restriction, exercise, which are included in the non-pharmacological part of treatment management.

Expert Recommendations to Bridge Gaps in Heart Failure Patient Support in the Middle East and Africa Region.

Heart failure (HF) remains a serious health and socioeconomic problem in the Middle East and Africa (MEA). The age-standardized prevalence rate for HF in the MEA region is higher compared to countries in Eastern Europe, Latin America, and Southeast Asia. Also cardiovascular-related deaths remain high compared to their global counterparts. Moreover, in MEA, 66% of HF readmissions are elicited by potentially preventable factors, including delay in seeking medical attention, nonadherence to HF medication, suboptimal discharge planning, inadequate follow-up, and poor social support. Patient support in the form of activation, counseling, and caregiver education has been shown to improve outcomes in patients with HF. A multidisciplinary meeting with experts from different countries across the MEA region was convened to identify the current gaps and unmet needs for patient support for HF in the region. The panel provided insights into the real-world challenges in HF patient support and contributed strategic recommendations for optimizing HF care.

The 6-minute walk test and fall risk in patients with heart failure: A cross-sectional study.

BACKGROUND: Given the increased risk of falls in patients with heart failure (HF), there is limited information in the literature about the possible relationship between fall risk and functional capacity. OBJECTIVE: To investigate the relationship between functional capacity and fall risk in patients with HF and to determine whether there are differences in clinical parameters between patients with and without fall risk. METHODS: The study included 64 patients with HF. The Activity-Specific Balance Confidence Scale (ABC) determined the fall risk. Functional capacity was assessed with the 6-minute walk test (6MWT). The Berg Balance Scale (BBS), the timed up-and-go test (TUG), and the five times sit-to-stand (5-STS) test were used to evaluate functional balance and mobility. Comorbidities and dyspnea perception were assessed with the Charlson Comorbidity Index (CCI) and modified Medical Research Council (mMRC), respectively. RESULTS: The 6MWT was associated with fall risk in logistic regression with an odds ratio of 0.979 (0.970-0.989, p < 0.001). Furthermore, the 6MWT had a discriminative value for increased fall risk in patients with HF, with a cutoff value of 248 m. Patients with increased fall risk had lower 6MWT distance, BBS, and gait speed, and higher CCI and mMRC, number of falls, duration of TUG and 5STS compared to patients with no increased fall risk (p < 0.05). CONCLUSIONS: The study results demonstrated that 6MWT may be a clinically useful tool in quickly identifying potential balance problems and increased fall risk by providing insight into fall risk/balance confidence in addition to assessing functional capacity.

Trends in heart failure between 2016 and 2022 in Türkiye (TRends-HF): a nationwide retrospective cohort study of 85 million individuals across entire population of all ages.

Background: Data on the burden of heart failure (HF) outside western countries are limited, but available data suggest it may present differently in other countries. The aim of this study was to examine the incidence, prevalence, and survival rates of HF in Türkiye, with a specific focus on how these rates vary according to age, sex, comorbidities, and socioeconomic status (SES). Methods: We harnessed the extensive National Electronic Database of the Turkish Ministry of Health, covering Turkey's entire population from January 1, 2016, to December 31, 2022, to identify 2,722,151 cases of HF and their associated comorbidities using ICD-10 codes. Analyzing the primary endpoint of all-cause mortality, our study utilized anonymized data to examine patient demographics, comorbidities, socioeconomic status, and survival patterns, employing statistical techniques to delve into relationships and trends. The data were segmented by gender, socioeconomic status, and age, involving cross-tabulations and statistical metrics to explore connections, odds ratios, and survival rates. Findings: The estimated prevalence of HF was 2.114% in Türkiye at the end of 2022, with an annual incidence ranging between 3.00 and 6.06 per 1000 person years. Females were older than males (69.8 ± 13.9 years vs. 66.8 ± 13.9 years, respectively). The most common comorbidities were congenital heart diseases and anemia under the age of 20, and hypertension and atherosclerotic cardiovascular disease in the adult population. Only 23.6% (643,159/2,722,151) of patients were treated with any triple guideline-directed medical therapy (GDMT) and 3.6% (96,751/2,722,151) of patients were on quadruple GDMT. The survival rates for patients with HF at 1, 5, and 7 years were 83.3% (95% CI: 83.2-83.3), 61.5% (95% CI: 61.4-61.6), and 57.7% (95% CI: 57.6-57.8) among females, and 82.1% (95% CI: 82.0-82.2), 58.2% (95% CI: 58.1-58.3), and 54.2% (95% CI: 54.0-54.3) among males. Despite a tendency for an increase from the highest to the lowest SES, the prevalence of HF and mortality were paradoxically lowest in the lowest SES region. Interpretation: The prevalence, incidence, and survival rates of HF in Türkiye were comparable to western countries, despite the notable difference of HF onset occurring 8-10 years earlier in the Turkish population. Drug usage statistics indicate there is a need for effective strategies to improve treatment with GDMT. Funding: None.

Left Bundle Branch Block-Induced Cardiomyopathy.

Left bundle branch block-induced cardiomyopathy is an increasingly recognized type of dilated cardiomyopathy identified in a minority but not negligible proportion of patients with newly diagnosed heart failure. However, it has not yet been included among the possible etiologies of dilated cardiomyopathies or among the unclassified cardiomyopathies. Although a few sets of diagnostic criteria have been proposed, currently there is a lack of universal consensus regarding diagnostic criteria. Some specific clinical features and electrocardiography, echocardiography, and cardiac magnetic resonance imaging findings are recommended to help physicians in the diagnosis of left bundle branch block-induced cardiomyopathy. In this review, prevalence, pathophysiological mechanisms, diagnostic criteria, diagnostic modalities, and specific features of left bundle branch block-induced cardiomyopathy have been addressed with attention to the differential diagnosis of other dilated cardiomyopathies.

The Frequency of Fabry Disease in Patients with Cardiac Hypertrophy of Various Phenotypes Including Prominent Papillary Muscle: The TUCARFAB Study in Turkey.

BACKGROUND: The present study aimed to identify the frequency of Fabry disease in patients with cardiac hypertrophy of unknown etiology and to evaluate demographic and clinical characteristics, enzyme activity levels, and genetic mutations at the time of diagnosis. METHODS: This national, multicenter, cross-sectional, single-arm, observational registry study was conducted in adult patients with a clinical echocardiographic diagnosis of left ventricular hypertrophy and/or the presence of prominent papillary muscle. In both genders, genetic analysis was performed by DNA Sanger sequence analysis. RESULTS: A total of 406 patients with left ventricular hypertrophy of unknown origin were included. Of the patients, 19.5% had decreased enzyme activity (≤2.5 nmol/mL/h). Although genetic analysis revealed GLA (galactosidase alpha) gene mutation in only 2  patients (0.5%), these patients were considered to have probable but not 'definite Fabry disease' due to normal lyso Gb3 levels and gene mutations categorized as variants of unknown significance. CONCLUSION: The prevalence of Fabry disease varies according to the characteristics of the population screened and the definition of the disease used in these trials. From cardiology perspective, left ventricular hypertrophy is the major reason to consider screening for Fabry disease. Enzyme testing, genetic analysis, substrate analysis, histopathological examination, and family screening should be performed, when necessary, for a definite diagnosis of Fabry disease. The results of this study underline the importance of the comprehensive use of these diagnostic tools to reach a definite diagnosis. The diagnosis and management of Fabry disease should not be based solely on the results of the screening tests.

Relationship between left atrial functions and ambulatory blood pressure variability in patients with heart failure and preserved ejection fraction.

Aim    The aim of this study was to investigate the relationship between left atrial (LA) abnormalities and ambulatory blood pressure variability (BPV) in heart failure with preserved ejection fraction (HFpEF) patients.Material and methods    In this single-center, prospective study, we included 187 patients with HFpEF. Eighteen patients with poor image quality were excluded from the study. BPV was evaluated using 24-h ambulatory blood pressure (BP) monitoring. The standard deviation of systolic BP (SBP-SD) was calculated to assess BPV. The patients were classified into two groups according to median SBP-SD (10.5 mm Hg).Results    Overall, 169 HFpEF patients (69.2% women, mean age 69.2±11 yrs) were evaluated. There were 98 patients (57.9%) with a SBP-SD greater than 10.5 mm Hg. Patients with higher SPB-SD had significantly higher left atrial stiffness (LASt) and lower LA reservoir strain (LASr) than those with low SPB-SD. LASt was correlated with 24 hr SBP-SD in both sinus rhythm (r= 0.35, p= 0.015) and atrial fibrillation patients (r= 0.32, p= 0.005). There were significant correlations between night-time SBP-SD and LASr (r=-0.23, p=0.045) in HFpEF with sinus rhythm. For all HFpEF patients, multiple regression analyses showed that 24-hr SBP-SD was correlated with LASt (coeff.=0.40, 95%CI= 0.52-5.25, P= 0.017).Conclusions    High BPV is associated with impaired LA function, especially for LASt and LASr. This study may provide insight for larger multicenter studies to evaluate the effects on outcomes in HFpEF.

Left atrial structure and function: association with blood pressure variability in pregnant women.

BACKGROUND: The aim of this study was to investigate the relationship between left atrial (LA) abnormalities and ambulatory blood pressure variability (BPV) in pregnant women and their relationship with hypertension-related clinical outcomes in pregnancy. METHODS: This single-center, prospective study included 119 pregnant women. All participants underwent 24-h ambulatory blood pressure (BP) monitoring and echocardiographic examination before 20 weeks of gestation. BPV was evaluated using 24-h ambulatory BP monitoring. SD of the mean of SBP (SBP-SD) and DBP variability was calculated as 24-h, daytime and nighttime SBP and DBP. The patients were classified into two groups based on median 24-h SBP-SD (11.3 mmHg). LA features of the patients were compared according to the high and low BPV groups. RESULTS: One hundred and nineteen pregnant women (mean age, 28.6 ± 5.2 years) were included in the study. The mean office SBP and DBP were 108.7 ± 15.4 mmHg and 68.2 ± 10.2 mmHg, respectively. In pregnant women with high BPV, even though BP is normal, reservoir and conduit LA functions have decreased and LA stiffness has increased. Gestational hypertension and composite outcomes were more common in pregnant women with high BPV. Among the LA parameters, the most associated with composite outcome was conduit LA function. CONCLUSION: In pregnancy, higher BPV is associated with worse LA function. The LA conduit strain offers potential value in predicting hypertension-related clinical outcomes in pregnancy.

Immunoadsorption therapy in refractory heart failure patients with dilated cardiomyopathy: a potential therapeutic option.

OBJECTIVE: Removal of cardiac autoantibodies by immunoadsorption might confer clinical improvement in dilated cardiomyopathy. In this pilot study, we investigated the efficacy and safety of immunoadsorption therapy in refractory heart failure patients with dilated cardiomyopathy. METHODS: This study consisted of 9 heart failure patients with dilated cardiomyopathy, NYHA III-IV, left ventricular ejection fraction <30%, unresponsive to heart failure therapy, and with cardiac autoantibodies. Patients underwent immunoadsorption therapy for five consecutive days using a tryptophan column. Changes in cardiac function (left ventricular ejection fraction, left ventricular end-diastolic diameter, left ventricular end-systolic diameter), exercise capacity (6-minute walk distance), neurohormonal (N-terminal pro-brain natriuretic peptide), proinflammatory (high-sensitive C-reactive protein), and myocardial (cardiac troponin-I), biochemical, and hematological variables were obtained at baseline and after 3 and 6 months of immunoadsorption therapy. RESULTS: Mean left ventricular ejection fraction and 6-minute walk distance significantly increased at 3 months (from 23.27±5.09 to 32.1±1.7%, p=0.01 for left ventricular ejection fraction and from 353±118 to 434±159 m, p=0.04 for 6-minute walk distance) and further increased at 6 months after immunoadsorption therapy (to 34.5±7.7%, p=0.02 for ejection fraction and to 441±136 m, p=0.04 for 6-minute walk distance). NT-proBNP level reduced from 1161(392.8-3034) to 385(116.1-656.5) ng/L (p=0.04), and high-sensitive C-reactive protein decreased from 9.74±0.96 to 4.3±5.8 mg/L (p=0.04) at 6 months. Left ventricular end-diastolic diameter (66.1±5.8 vs. 64.7±8.9 mm) and left ventricular end-systolic diameter (56.1±8.6 vs. 52.3±10.8 mm) tended to decrease but did not reach statistical significance. No significant worsening was observed in creatinine, cardiac troponin-I, and hemoglobin levels after the immunoadsorption procedure. CONCLUSION: In dilated cardiomyopathy patients with refractory heart failure, immunoadsorption may be considered a potentially useful therapeutic option to improve a patient's clinical status.

Immunoadsorption therapy in refractory heart failure patients with dilated cardiomyopathy: a potential therapeutic option

SUMMARY OBJECTIVE: Removal of cardiac autoantibodies by immunoadsorption might confer clinical improvement in dilated cardiomyopathy. In this pilot study, we investigated the efficacy and safety of immunoadsorption therapy in refractory heart failure patients with dilated cardiomyopathy. METHODS: This study consisted of 9 heart failure patients with dilated cardiomyopathy, NYHA III-IV, left ventricular ejection fraction <30%, unresponsive to heart failure therapy, and with cardiac autoantibodies. Patients underwent immunoadsorption therapy for five consecutive days using a tryptophan column. Changes in cardiac function (left ventricular ejection fraction, left ventricular end-diastolic diameter, left ventricular end-systolic diameter), exercise capacity (6-minute walk distance), neurohormonal (N-terminal pro-brain natriuretic peptide), proinflammatory (high-sensitive C-reactive protein), and myocardial (cardiac troponin-I), biochemical, and hematological variables were obtained at baseline and after 3 and 6 months of immunoadsorption therapy. RESULTS: Mean left ventricular ejection fraction and 6-minute walk distance significantly increased at 3 months (from 23.27±5.09 to 32.1±1.7%, p=0.01 for left ventricular ejection fraction and from 353±118 to 434±159 m, p=0.04 for 6-minute walk distance) and further increased at 6 months after immunoadsorption therapy (to 34.5±7.7%, p=0.02 for ejection fraction and to 441±136 m, p=0.04 for 6-minute walk distance). NT-proBNP level reduced from 1161(392.8-3034) to 385(116.1-656.5) ng/L (p=0.04), and high-sensitive C-reactive protein decreased from 9.74±0.96 to 4.3±5.8 mg/L (p=0.04) at 6 months. Left ventricular end-diastolic diameter (66.1±5.8 vs. 64.7±8.9 mm) and left ventricular end-systolic diameter (56.1±8.6 vs. 52.3±10.8 mm) tended to decrease but did not reach statistical significance. No significant worsening was observed in creatinine, cardiac troponin-I, and hemoglobin levels after the immunoadsorption procedure. CONCLUSION: In dilated cardiomyopathy patients with refractory heart failure, immunoadsorption may be considered a potentially useful therapeutic option to improve a patient's clinical status.

Usefulness of Age, Creatinine and Ejection Fraction - Modification of Diet in Renal Disease Score for Predicting Survival in Patients with Heart Failure. / Utilidade da Idade, Creatinina e Fração de Ejeção - Modificação da Dieta no Escore de Doença Renal para Prever a Sobrevivência em Pacientes com Insuficiência Cardíaca.

BACKGROUND: Central Illustration: Usefulness of Age, Creatinine and Ejection Fraction - Modification of Diet in Renal Disease Score for Predicting Survival in Patients with Heart Failure Summary of the study design and key findings. ACEF: Age, creatinine and ejection fraction, MDRD: Modified Diet in Renal Disease. While many risk models have been developed to predict prognosis in heart failure (HF), these models are rarely useful for the clinical practitioner as they include multiple variables that might be time-consuming to obtain, they are usually difficult to calculate, and they may suffer from statistical overfitting. OBJECTIVES: To investigate whether a simpler model, namely the ACEF-MDRD score, could be used for predicting one-year mortality in HF patients. METHODS: 748 cases within the SELFIE-HF registry had complete data to calculate the ACEF-MDRD score. Patients were grouped into tertiles for analyses. For all tests, a p-value <0.05 was accepted as significant. RESULTS: Significantly more patients within the ACEF-MDRD high tertile (30.0%) died within one year, as compared to other tertiles (10.8% and 16.1%, respectively, for ACEF-MDRD low and ACEF-MDRD med , p<0.001 for both comparisons). There was a stepwise decrease in one-year survival as the ACEF-MDRD score increased (log-rank p<0.001). ACEF-MDRD was an independent predictor of survival after adjusting for other variables (OR: 1.14, 95%CI:1.04 - 1.24, p=0.006). ACEF-MDRD score offered similar accuracy to the GWTG-HF score for predicting one-year mortality (p=0.14). CONCLUSIONS: ACEF-MDRD is a predictor of mortality in patients with HF, and its usefulness is comparable to similar yet more complicated models.

FUNDAMENTO: Figura Central: Utilidade da Idade, Creatinina e Fração de Ejeção - Modificação da Dieta no Escore de Doença Renal para Prever a Sobrevivência em Pacientes com Insuficiência Cardíaca Resumo do desenho do estudo e principais conclusões. ACEF: Idade, creatinina e fração de ejeção (Age, creatinine and ejection fraction) MDRD: Dieta Modificada em Doença Renal (Modified Diet in Renal Disease). Embora muitos modelos de risco tenham sido desenvolvidos para prever o prognóstico na insuficiência cardíaca (IC), esses modelos raramente são úteis para o clínico, pois incluem múltiplas variáveis que podem ser demoradas para serem obtidas, são geralmente difíceis de calcular e podem sofrer de overfitting estatístico. OBJETIVOS: Investigar se um modelo mais simples, nomeadamente o escore ACEF-MDRD, poderia ser usado para prever a mortalidade em um ano em pacientes com IC. MÉTODOS: 748 casos do registro SELFIE-HF tinham dados completos para calcular o escore ACEF-MDRD. Os pacientes foram agrupados em tercis para análise. Para todos os testes, um valor de p <0,05 foi aceito como significativo. RESULTADOS: Significativamente mais pacientes dentro do tercil ACEF-MDRD alto (30,0%) morreram dentro de um ano, em comparação com outros tercis (10,8% e 16,1%, respectivamente, para ACEF-MDRD baixo e ACEF-MDRD med , p<0,001 para ambas as comparações). Houve uma diminuição gradual na sobrevida em um ano à medida que o escore ACEF-MDRD aumentou (log-rank p<0,001). ACEF-MDRD foi preditor independente de sobrevida após ajuste para outras variáveis (OR: 1,14, IC95%:1,04 ­ 1,24, p=0,006). O escore ACEF-MDRD ofereceu precisão semelhante ao escore GWTG-HF para prever a mortalidade em um ano (p=0,14). CONCLUSÕES: ACEF-MDRD é um preditor de mortalidade em pacientes com IC e sua utilidade é comparável a modelos semelhantes, porém mais complicados.

Thrombolysis in Myocardial Infarction Risk Index Predicts 1-Year Mortality in Patients with Heart Failure: An Analysis of the SELFIE-TR Study.

OBJECTIVE: Predicting outcomes is an essential part of evaluation of patients with heart failure (HF). While there are multiple individual laboratory and imaging variables as well as risk scores available for this purpose, they are seldom useful during the initial evaluation. In this analysis, we aimed to elucidate the predictive usefulness of Thrombolysis in Myocardial Infarction Risk Index (TIMI-RI), a simple index calculated at the bedside with three commonly available variables, using data from a multicenter HF registry. SUBJECTS AND METHODS: A total of 728 patients from 23 centers were included in this analysis. Data on hospitalizations and mortality were collected by direct interviews, phone calls, and electronic databases. TIMI-RI was calculated as heart rate × (age/10)2/systolic pressure. Patients were divided into three equal tertiles to perform analyses. RESULTS: Rehospitalization for HF was significantly higher in patients within the 3rd tertile, and 33.5% of patients within the 3rd tertile had died within 1-year follow-up as compared to 14.5% of patients within the 1st tertile and 15.6% of patients within the 2nd tertile (p < 0.001, log-rank p < 0.001 for pairwise comparisons). The association between TIMI-RI and mortality remained significant (OR: 1.74, 95% CI: 1.05-2.86, p = 0.036) after adjustment for other variables. A TIMI-RI higher than 33 had a negative predictive value of 84.8% and a positive predictive value of 33.8% for prediction of 1-year mortality. CONCLUSION: TIMI-RI is a simple index that predicts 1-year mortality in patients with HF; it could be useful for rapid evaluation and triage of HF patients at the time of initial contact.

Heart failure with non-reduced ejection fraction: Epidemiology, pathophysiology, phenotypes, diagnosis and treatment approaches.

Heart failure (HF) has been classified as reduced ejection fraction (HFrEF), mildly reduced ejection fraction (HFmrEF) and preserved ejection fraction (HFpEF) by the recent HF guidelines. In addition, HF with improved ejection fraction has been defined as a subgroup of HFrEF. In HFrEF, diagnostic workup and evidence-based pharmacological and device-based therapies have been well established. However, HFpEF, which comprises almost half of the HF population, represents significant uncertainties regarding its pathophysiology, clinical phenotypes, diagnosis and treatment. Diagnostic criteria of HFpEF have been changed a few times over the years and still remained a matter of debate. New paradigms including a prominent role of co-morbidities, inflammation, endothelial dysfunction have been proposed in its pathophysiology. As a complex, multifactorial syndrome HFpEF consists of many overlapping clinical and hemodynamic phenotypes. In contrast to HFrEF, clinical outcomes of HFpEF have not improved over the last decades due to lack of proven effective therapies. Although HFrEF and HFpEF have different clinical spectrums and proposed pathophysiological mechanisms, there is no clear defining syndrome postulated for HFmrEF. Clinical characteristics and risk factors of HFmrEF overlap with HFrEF and HFpEF. HFmrEF is also referred as a transitional zone for dynamic temporal changes in EF. So, HFpEF and HFmrEF, both namely HF with non-reduced ejection fraction (HF-NEF), have some challenges in the management of HF. The purpose of this paper is to provide a comprehensive review including epidemiology, pathophysiology, clinical presentation and phenotypes of HF-NEF and to guide clinicians for the diagnosis and therapeutic approaches based on the available data in the literature.

Cost-of-disease of Heart Failure in Turkey: A Delphi Panel-based Analysis of Direct and Indirect Costs.

Background: Heart failure (HF) is considered a significant public health issue with a substantial and growing epidemiologic and economic burden in relation to longer life expectancy and aging global population. Aims: To determine cost-of-disease of heart failure (HF) in Turkey from the payer perspective. Study Design: Cross-sectional cost of disease study. Methods: In this cost-of-disease study, annual direct and indirect costs of management of HF were determined based on epidemiological, clinical and lost productivity inputs provided by a Delphi panel consisted of 11 experts in HF with respect to ejection fraction (EF) status (HF patients with reduced EF (HFrEF), mid-range EF (HFmrEF) and preserved EF (HFpEF)) and New York Heart Association (NYHA) classification. Direct medical costs included cost items on outpatient management, inpatient management, medications, and non-pharmaceutical treatments. Indirect cost was calculated based on the lost productivity due to absenteeism and presenteeism. Results: 51.4%, 19.5%, and 29.1% of the patients were estimated to be HFrEF, HFmrEF, and HFpEF patients, respectively. The total annual direct medical cost per patient was $887 and non-pharmaceutical treatments ($373, 42.1%) were the major direct cost driver. Since an estimated nationwide number of HF patients is 1,128,000 in 2021, the total annual national economic burden of HF is estimated to be $1 billion in 2021. The direct medical cost was higher in patients with HFrEF than in those with HFmrEF or HFpEF ($1,147 vs. $555 and $649, respectively). Average indirect cost per patient was calculated to be $3,386 and was similar across HFrEF, HFmrEF and HFpEF groups, but increased with advanced NYHA stage. Conclusion: Our findings confirm the substantial economic burden of HF in terms of both direct and indirect costs and indicate that the non-pharmaceutical cost is the major direct medical cost driver in HF management, regardless of the EF status of HF patients.

Pre-Discharge and Post-Discharge Management and Treatment Optimization in Acute Heart Failure.

Acute heart failure is associated with high mortality and rehospitalization rates and required urgent evaluation and early initiation or intensification of therapy. The risk of death and heart failure rehospitalization is greatest in the early post-discharge period, particularly within the first 3-6 months, and declines over time, which is referred as a vulnerable period of acute heart failure hospitalization. Therefore, implementation of guidelines-directed optimal therapy is not only so crucial in the acute phase but also very important in the pre-discharge and early post- discharge period in reducing mortality and rehospitalization rates. The pre-discharge period represents a window of opportunity for treatment optimization which includes to eliminate congestion, to treat comorbidities or precipitating factors, and to initiate or uptitrate oral ther- apy before discharge. Early assessment in the post-discharge period based on clinical evalu- ation and laboratory exams, further optimization of disease-modifying therapy is associated with lower 30-day hospitalization for heart failure. In clinical practice, clinicians usually focus on acute phase intravenous medications and short-term device therapies and, in fact, neglect short- and long-term comprehensive approaches. This paper reviews management strategies that may help reduce mortality and heart failure rehospitalizations in pre-discharge and post- discharge periods and include adopting holistic approaches for heart failure, increasing optimi- zation of evidence-based therapies, treating cardiac and noncardiac comorbidities, improving care transitions, monitoring, and disease management.