Annual evolution of the prescription of drugs with prognostic implications in acute decompensated heart failure with reduced ejection fraction.

BACKGROUND: Quadruple therapy (renin angiotensin system inhibitors, beta-blockers, mineralocorticoid receptor antagonists and sodium/glucose cotransporter type 2 inhibitors [SGLT2i]) has become the current prognostic modifying treatment for heart failure (HF) with reduced ejection fraction (HFrEF). This study aimed to analyse the prescription´s evolution of this combination therapy, the analysis of each pharmacological group and the differences according to HF subgroups. METHODS: Retrospective analysis of consecutive patients admitted for cardiac decompensation. Inclusion period: from 1-1-2020 to 12-31-2022. Patients with left ventricular ejection fraction > 40% and deceased during admission were excluded. Finally, 602 patients were included. These were divided into: (a) de novo HF without previous heart disease (n:108), (b) de novo with previous heart disease (n:107), and (c) non-de novo (n:387). RESULTS: Over the study time, all pharmacological groups experienced an increase in drugs prescription (p < 0.001). The group with the largest prescription rate increase was SGLT2i (2020:20%, 2021:42.9%, 2022:70.4%; mean increase 47.2%). The discharge rate prescription of quadruple therapy increased progressively (2020:7.4%, 2021:21.1%, 2022:32.5%; mean increase 21.9%). The subgroup with the highest combined prescription in 2022 was de novo with previous heart disease (43.9%). CONCLUSION: The pharmacological group with the largest prescription´s rate increase was SGLT2i. The percentage of patients discharged on quadruple therapy has progressed significantly in recent years, although it remains low. The most optimised subgroup at discharge was that of de novo HF with previous heart disease.

Epidemiological Study of Tricuspid Regurgitation After Cardiac Transplantation. Does it Influence Survival?

Background: Tricuspid valve disease is the most frequent valvulopathy after heart transplantation (HTx). Evidence for the negative effect of post-transplant tricuspid regurgitation (TR) on survival is contradictory. The aim of this study was to analyze the causes of post-transplant TR and its effect on overall mortality. Methods: This is a retrospective observational study of all transplants performed in two Spanish centers (1009 patients) between 2000 and 2019. Of the total number of patients, 809 had no TR or mild TR and 200 had moderate or severe TR. The etiology of TR was analyzed in all cases. Results: The prevalence of moderate and severe TR was 19.8%. The risk of mortality was greater when TR was caused by early primary graft failure (PGF) or rejection (p < 0.05). TR incidence was related to etiology: incidence of PGF-induced TR was higher in the first period, while TR due to rejection and undefined causes occurred more frequently in three periods: in the first year, in the 10-14-year period following HTx, and in the long term (16-18 years). In the multivariable analysis, TR was significantly associated with mortality/retransplantation (HR:1.04, 95% CI:1.01-1.07, p:0.02). Conclusion: The development of TR after HTx is relatively frequent. The annual incidence depends on TR severity and etiology. The risk of mortality is greater in severe TR due to PGF or rejection.

Does the calcineurin inhibitor have influence on cytomegalovirus infection in heart transplantation?

Cytomegalovirus (CMV) infection is a major cause of morbidity and mortality in heart transplant (HTx). Our aim was to analyze the rate of CMV infection in HTx patients receiving treatment with cyclosporine (CsA) or tacrolimus (Tac). Ninety-five patients were randomized to receive either CsA (53.7%) or Tac (46.3%). We performed prophylaxis with valganciclovir in patients with the highest risk of CMV infection. We considered CMV infection as an increased viral load or the presence of CMV in histological samples. We analyzed baseline characteristics, CMV infection, and other complications. Event-free rates were calculated using the Kaplan-Meier method. There were no significant differences in baseline characteristics between both groups. CMV infection was detected in 31.6% of patients (in 66.7% due to asymptomatic replication). The group treated with Tac had a lower rate of CMV infection (15.9% vs. 45.1%, p = 0.002) and longer CMV infection-free survival time (1440 vs. 899 d, p = 0.001). No differences were observed in the complications analyzed in both groups. The independent risk factors for infection identified in the multivariate analysis were treatment with CsA and bacterial infections. This was the first study to demonstrate a lower rate of CMV infection in patients treated with Tac vs. those treated with CsA after HTx.

Genotype and allele frequencies of drug-metabolizing enzymes and drug transporter genes affecting immunosuppressants in the Spanish white population.

Interpatient variability in drug response can be widely explained by genetically determined differences in metabolizing enzymes, drug transporters, and drug targets, leading to different pharmacokinetic and/or pharmacodynamic behaviors of drugs. Genetic variations affect or do not affect drug responses depending on their influence on protein activity and the relevance of such proteins in the pathway of the drug. Also, the frequency of such genetic variations differs among populations, so the clinical relevance of a specific variation is not the same in all of them. In this study, a panel of 33 single nucleotide polymorphisms in 14 different genes (ABCB1, ABCC2, ABCG2, CYP2B6, CYP2C19, CYP2C9, CYP3A4, CYP3A5, MTHFR, NOD2/CARD15, SLCO1A2, SLCO1B1, TPMT, and UGT1A9), encoding for the most relevant metabolizing enzymes and drug transporters relating to immunosuppressant agents, was analyzed to determine the genotype profile and allele frequencies in comparison with HapMap data. A total of 570 Spanish white recipients and donors of solid organ transplants were included. In 24 single nucleotide polymorphisms, statistically significant differences in allele frequency were observed. The largest differences (>100%) occurred in ABCB1 rs2229109, ABCG2 rs2231137, CYP3A5 rs776746, NOD2/CARD15 rs2066844, TPMT rs1800462, and UGT1A9 rs72551330. In conclusion, differences were recorded between the Spanish and other white populations in terms of allele frequency and genotypic distribution. Such differences may have implications in relation to dose requirements and drug-induced toxicity. These data are important for further research to help explain interindividual pharmacokinetic and pharmacodynamic variability in response to drug therapy.

Circulating long non-coding RNAs detection after heart transplantation and its accuracy in the diagnosis of acute cardiac rejection.

Long non-coding RNAs (lncRNAs) are closely implicated in biological processes and diseases with high inflammatory components. These molecules exhibit significant temporal and tissue specificity. However, the expression and function of lncRNAs have not been studied in patients after heart transplantation. Thus, we aimed to identify circulating lncRNAs in these patients and evaluate their diagnostic capacity as potential biomarkers for the non-invasive detection of acute cellular rejection (ACR). For them, we performed a transcriptomic study based on ncRNA-seq technology to detect lncRNAs in serum samples, matched to routine endomyocardial biopsies, from patients without rejection episode (0R, n = 12) and with mild (1R, n = 16) or moderate-severe (≥ 2R, n = 12) ACR. We identified 11,062 circulating lncRNAs in the serum of patients after heart transplantation. Moreover, 6 lncRNAs showed statistically significant expression when the different ACR grades were compared. Among them, AC008105.3, AC006525.1, AC011455.8, AL359220.1, and AC025279.1 had relevant diagnostic capacity for detection of ≥ 2R (AUC of 0.850 to 1.000) and 1R (AUC of 0.750 to 0.854) grades, along with high specificity and positive predictive values (≥ 83%). In addition, AL359220.1 and AC025279.1 were independent predictors for the presence of moderate-severe ACR (odds ratio = 31.132, p < 0.01 and C statistic = 0.939, p < 0.0001; odds ratio = 18.693, p < 0.05 and C statistic = 0.902, p < 0.001; respectively). In conclusion, we describe, for the first time, circulating lncRNAs after heart transplantation as potential candidates for non-invasive detection of ACR. AL359220.1 and AC025279.1 showed excellent diagnostic capability correlating with the severity episode and were strong independent predictors of rejection.

Usefulness of biomarkers to predict prognosis after heart transplant.

INTRODUCTION AND OBJECTIVES: Heart transplant (HT) represents a major physiological stress, resulting in elevated levels of analytical biomarkers. This study aimed to determine whether changes in biomarker levels after HT can identify patients with a poor prognosis. METHODS: A prospective longitudinal noninterventional study was conducted in 149 consecutive patients undergoing HT from July 2017 to July 2023. Biomarkers were assessed before HT and at 6, 24, 48, 72, and 96hours after HT. The biomarkers analyzed were high-sensitivity troponin T, N-terminal pro-B-type natriuretic peptide (NT-proBNP), creatinine, and lactic acid. The primary outcome was a composite of death and severe primary graft failure (PGF). RESULTS: NT-proBNP and troponin levels remained highly elevated throughout the period and stabilized from the first 24hours post-HT. Lactate levels stabilized after the first 24hours, and creatinine from the second day onward. Exitus occurred in 23 (15%) of the patients, and severe PGF in 26 (17%). All biomarkers were significantly associated with the incidence of the combined event (P <.0001). Receiver operating characteristic curve analysis at 24hours showed significant areas under the curve (P=.0001). The greatest discriminatory power was observed for the NT-proBNP curve. A value of 10 000 pg/mL had a sensitivity of 90% and specificity of 80%. CONCLUSIONS: A significant elevation of post-HT analytical biomarkers was associated with mortality and/or severe PGF. Among the biomarkers analyzed, NT-proBNP was the most accurate in classifying patients.

Practical Requirements for the Development of an Advanced Cardiorenal Unit.

BACKGROUND: Heart failure is frequently associated with kidney disease, and patients with kidney disease are at increased risk of heart failure. The co-occurrence of both entities not only significantly increases morbidity and mortality but also complicates therapy. SUMMARY: Cardiorenal syndrome often requires a broad, comprehensive, and multidisciplinary approach. As a result, a need has arisen to create specialized cardiorenal units that allow for rigorous and personalized management of this condition. Moreover, in some cases, cardiorenal syndrome is more complex, owing to an acute and critical situation that requires the concept of the cardiorenal unit to be extended toward advanced diagnostic and therapeutic positions, thus confirming the need for an advanced cardiorenal unit. The creation of these units constitutes a real challenge, necessitating a specific multilevel action plan, covering governance and management, type of patient, personnel requirements, service portfolio, care process, information systems, and other resources. Specific lines of action must be proposed for each of the relevant points in order to facilitate development of these units, together with continuous evaluation of unit activity through specific indicators, and to detect areas for improvement. KEY MESSAGES: This study addresses the conditions and organizational characteristics that enable the creation, development, and continuous improvement of advanced cardiorenal units.

Maintained renin-angiotensin-aldosterone system inhibitor therapy with sodium zirconium cyclosilicate following a hyperkalaemia episode: a multicountry cohort study.

Background: This observational cohort study compared the likelihood of maintained (stabilized/up-titrated) renin-angiotensin-aldosterone system inhibitor (RAASi) therapy at 6 months following hyperkalaemia in patients with chronic kidney disease (CKD) and/or heart failure (HF) from the USA, Japan and Spain who received sodium zirconium cyclosilicate (SZC) for at least 120 days, relative to those with no prescription for a potassium (K+) binder. Methods: Using health registers and hospital medical records, patients with CKD and/or HF receiving RAASi therapy who experienced a hyperkalaemia episode were identified. Propensity score (PS) matching (1:4) was applied to balance the SZC cohort to the no K+ binder cohort on baseline characteristics. Logistic regression analysis was performed to compare the odds of maintained RAASi therapy at 6 months in the SZC versus no K+ binder cohorts. Results: The PS-matched SZC cohort included 565 (USA), 776 (Japan) and 56 (Spain) patients; the no K+ binder cohort included 2068, 2629 and 203 patients, respectively. At 6 months, 68.9% (USA), 79.9% (Japan) and 69.6% (Spain) in the SZC cohorts versus 53.1% (USA), 56.0% (Japan) and 48.3% (Spain) in the no K+ binder cohorts had maintained RAASi therapy. Meta-analysed across countries, the odds ratio of maintained RAASi therapy in the SZC cohort versus no K+ binder cohort was 2.56 (95% confidence interval 1.92-3.41; P < .0001). Conclusions: In routine clinical practice across three countries, patients treated with SZC were substantially more likely to maintain guideline-concordant RAASi therapy at 6 months following hyperkalaemia relative to patients with no K+ binder treatment.

Hyperkalemia-Related RAASi Reduction and Estimated Number Needed to Treat to Avoid a First Hospitalization by Maintaining RAASi.

BACKGROUND: Renin-angiotensin-aldosterone system inhibitor (RAASi) therapy provides cardiorenal protection but is often down-titrated or discontinued following a hyperkalemia episode. This observational study describes the extent of hyperkalemia-related RAASi reduction in patients with chronic kidney disease (CKD) and/or heart failure (HF), and estimates the number needed to treat (NNT) to avoid a first hospitalization if RAASi had been maintained at the prior dose. METHODS: Healthcare registers and claims data from Germany, Spain, Sweden, and the UK were used to identify non-dialysis patients with CKD and/or HF who had a hyperkalemia episode while on RAASi. Patients whose RAASi therapy was reduced (down-titrated/discontinued) after the hyperkalemia episode were propensity score (PS)-matched to those with maintained RAASi, and their risks of a hospitalization within 6 months were estimated using the Kaplan-Meier method. Based on the absolute difference in this 6-month risk, the NNT framework was applied to estimate the number of patients who needed to have maintained instead of reduced their RAASi to avoid a first hospitalization during this period. RESULTS: Overall, 40,059 patients from Germany, Spain, Sweden, and the UK were included. Presence of CKD at baseline was similar across countries (72%-92%), while HF was less common in Spain (18%) versus other countries (32%-71%). After the hyperkalemia episode, RAASi was reduced in 25%-57% of patients. Following PS matching, the 6-month risk of hospitalization was consistently higher in those with reduced versus maintained RAASi; the absolute risk difference ranged from 2.7% to 7.3%. Applying the NNT framework, these data suggest that a first hospitalization within 6 months could potentially have been avoided if 25 patients had maintained instead of reduced their RAASi. CONCLUSIONS: Our findings suggest a potential for avoiding a first hospitalization, even within a short time frame, by increasing adherence to guidelines to maintain instead of reduce RAASi after a hyperkalemia episode.

Metabolic syndrome in heart transplantation: impact on survival and renal function.

The aim of our study was to analyze the early presence of metabolic syndrome (MS) in heart transplant (HTx) patients, and to assess its long-term impact on survival and renal function. From January 2000 to October 2011, 253 consecutive HTx patients who survived more than 90 days were included. MS was diagnosed if patients met revised NCEP-ATP III criteria at HTx or within 3 months post-HTx. The prevalence of MS was 41.9%. Patients with MS had greater overall mortality after a mean follow-up of 1700 ± 979 days (log-rank test, P = 0.020). In the multivariate analysis, and subject to a minimum survival of 90 days, the only independent predictor variables of long-term mortality were the presence of MS (OR, odds ratio 2.087, P = 0.032), and rejection episodes (OR 1.833, P = 0.001). Patients with MS had worse renal function at baseline both in plasma creatinine (1.19 ± 0.44 vs. 1.03 ± 0.29 mg/dl, P = 0.002) and glomerular filtration rate estimated by modified diet in renal disease (73.60 ± 26.76 vs. 87.30 ± 43.55 ml/min/1.73 m(2) , P = 0.005), whereas progressive impairment of renal function was of equal magnitude in both groups. The presence of MS prior to transplant or its development within the first 3 months identified a subgroup at greater risk of mortality and long-term renal dysfunction.

Impact of basal heart rate on long-term prognosis of heart transplant patients.

Previous studies in patients with heart failure have shown that an elevated basal heart rate (HR) is associated with a poor outcome. Our aim with this study was to investigate if this relationship is also present in heart transplantation (HTx) recipients. From 2003 until 2010, 256 HTx performed in our center were recruited. Patients who required pacemaker, heart-lung transplants, pediatrics, retransplants, and those patients with a survival of less than 1 year were excluded. The final number included in the analysis was 191. Using the HR obtained by EKG during elective admission at 1 year post-HTx and the survival rate, an ROC-curve was performed. The best point under the curve was achieved with 101 beats per minute (bpm), so patients were divided in two groups according to their HR. A comparison between survival curves of both groups was performed (Kaplan-Meier). Subsequently, a multivariate analysis considering HR and other variables with influence on survival according to the literature was carried out. A total of 136 patients were included in the group with HR ≤100 bpm, and 55 in the one with HR >100 bpm. There were no basal differences in both groups except for primary graft failure, which was more frequent in the >100 bpm group (30.9 vs. 17%, P = 0.033). Patients with ≤100 bpm had a better long prognosis (P < 0.001). The multivariate analysis proved that high HR was an independent predictor of mortality. Our study shows that HR should be considered as a prognosis factor in HTx patients.

Is the Benefit of Treating Iron Deficiency Greater in Acute Heart Failure with Renal Dysfunction?

BACKGROUND: This study aims to analyse whether in acute heart failure (AHF) with iron deficiency (ID), the administration of ferric carboxymaltose (FCM) produces a greater benefit in renal dysfunction. METHODS: A total of 812 consecutive patients admitted for AHF and ID were studied. Untreated (n:272) and treated (n:540) patients were compared. The six-month prevalence of a combined event (readmission for HF, all-cause death, and emergency department visit for decompensation) was analysed. Three grades of renal dysfunction (KDIGO) were compared, Group 1 (grades 1 and 2), Group 2 (grades 3a and 3b), and Group 3 (grades 4 and 5). RESULTS: There were differences in sex distribution (untreated group: males 39.7% vs. treated group: males 51.9%; p < 0.001). Sex-adjusted combined event analysis showed a greater benefit in Group 1 (OR: 0.31, 95% CI:0.19-0.5; p < 0.001) and Group 2 (OR: 0.23, 95% CI:0.14-0.38; p < 0.001), but not in Group 3 (OR: 0.51, 95% CI:0.17-0.55; p: 0.237). CONCLUSIONS: The administration of FCM in patients with AHF and ID reduces the combined event analysed. The benefit is greater when renal dysfunction is present, except in very advanced degrees where no significant benefit is obtained.

Clinical phenotypes according to diuretic combination in acute heart failure.

BACKGROUND: The treatment of congestion in heart failure (HF) is a challenge despite the therapeutic arsenal available. The aim of this study was to analyze different combinations of diuretics used to resolve congestion in patients admitted for decompensated HF and to define clinical profiles according to these treatments. METHODS: Single-center study of 1,559 patients admitted for decompensated HF was done between 2016 and 2020. Patients were grouped according to the diuretic combination that led to clinical stabilization and discharge from the hospital: (1) Loop diuretic. (2) Loop diuretic + distal tubule (antialdosterone ± thiazides). (3) Loop diuretic + distal + proximal tubule (acetazolamide ± SGLT2 inhibitor). (4) Loop diuretic + distal tubule + collecting duct (tolvaptan). (5) Loop diuretic + distal + proximal + collecting duct. Based on these diuretic combinations, profiles with clinical, analytical, and echocardiographic differences were established. RESULTS: There were more previous hospitalizations in groups 4 and 5 (p = 0.001) with a predominance of pulmonary congestion in profiles 1 and 2 and systemic congestion in 3, 4, and 5. Creatinine and CA125 were higher in profiles 4 and 5 (p = 0.01 and p = 0.0001), with no differences in NT-proBNP. Profiles 4 and 5 had a higher proportion of dilatation and depression of right ventricular (p = 0.0001) and left ventricular (p = 0.003) function. Diuretic therapy-defined groups showed difference in clinical characteristics. CONCLUSIONS: The diuretic treatment used identifies five clinical profiles according to the degree of congestion, renal function, CA125, and right ventricular functionality. These profiles would guide the best diuretic treatment on admission.

Alpha-cardiac Actin Serum Expression Levels Detect Acute Cellular Rejection in Heart Transplant Patients.

BACKGROUND: Given the central role of sarcomeric dysfunction in cardiomyocyte biology and sarcomere alterations described in endomyocardial biopsies of transplant patients with rejection, we hypothesized that the serum expression levels of genes encoding sarcomeric proteins were altered in acute cellular rejection (ACR). The aim of this study is to identify altered sarcomere-related molecules in serum and to evaluate their diagnostic accuracy for detecting rejection episodes. METHODS: Serum samples from transplant recipients undergoing routine endomyocardial biopsies were included in an RNA sequencing analysis (n = 40). Protein concentrations of alpha-cardiac actin were determined using a specific enzyme-linked immunoassay (n = 80). RESULTS: We identified 17 sarcomeric genes differentially expressed in patients with clinically relevant rejection (grade ≥2R ACR). A receiver operating characteristic curve was done to assess their accuracy for ACR detection and found that 6 relevant actins, myosins, and other sarcomere-related genes showed great diagnostic capacity with an area under the curve (AUC) > 0.800. Specifically, the gene encoding alpha-cardiac actin ( ACTC1 ) showed the best results (AUC = 1.000, P < 0.0001). We determine ACTC1 protein levels in a larger patient cohort, corroborating its overexpression and obtaining a significant diagnostic capacity for clinically relevant rejection (AUC = 0.702, P < 0.05). CONCLUSIONS: Sarcomeric alterations are reflected in peripheral blood of patients with allograft rejection. Because of their precision to detect ACR, we propose sarcomere ACTC1 serum expression levels as potential candidate for to be included in the development of molecular panel testing for noninvasive ACR detection.

Overview of the Treatment of Congestion in Heart Failure.

Heart failure is a major problem in developed countries, leading to a high number of hospitalizations and healthcare costs. The most common symptom of heart failure is congestion, which is also the primary reason for hospitalization. Diuretics, particularly loop diuretics, are the cornerstone of the treatment of congestion. Likewise, there are other types of diuretics with different pathways of action, bioavailability profiles, adverse reactions, and effects on the cardiovascular and renal systems. Moreover, in recent years, new therapeutic alternatives have been proposed for challenging cases of diuretic resistance, such as ultrafiltration through peripheral access or peritoneal dialysis. The main objective of this article is to provide a step-guided approach to the management of congestion in patients with heart failure in order to guide the medical practice. Despite the significant amount of research published in recent years, there are no clear algorithms for managing acute heart failure. Diuretics remain the primary treatment of acute heart failure, and nephron blockade is key, but new therapies are emerging, and ongoing research is needed to develop better strategies for managing this condition.

Combining Serum miR-144-3p and miR-652-3p as Potential Biomarkers for the Early Diagnosis and Stratification of Acute Cellular Rejection in Heart Transplantation Patients.

BACKGROUND: There is a dire need for specific, noninvasive biomarkers that can accurately detect cardiac acute cellular rejection (ACR) early. Previously, we described miR-144-3p as an excellent candidate for detecting grade ≥2R ACR. Now, we investigated the combination of miR-144-3p with miR-652-3p, other differentially expressed serum miRNA we previously described, to improve diagnostic accuracy mainly in mild rejection to avoid reaching severe stages. METHODS: We selected miR-652-3p from a preliminary RNA-seq study to be validated by reverse transcription-quantitative polymerase chain reaction on 212 consecutive serum samples from transplantation recipients undergoing routine endomyocardial biopsies to subsequently combine them with miR-144-3p results and investigate their diagnostic capability. RESULTS: We confirmed the miR-652-3p overexpression (P < 0.0001) and its capability to discriminate between patients with and without ACR of any grade (P < 0.0001). The combined serum levels of miR-144-3p and miR-652-3p were significantly higher in patients with rejection regardless of posttransplantation time (P < 0.0001). This combination resulted in a diagnostic efficacy for 1R (area under the curve = 0.794) and ≥2R (area under the curve = 0.892; P < 0.0001) that was superior to each biomarker alone. Furthermore, it was a strong independent predictor of ACR for 1R (odds ratio of 10.950; P < 0.0001) and ≥2R (odds ratio of 14.289; P < 0.01). CONCLUSIONS: We demonstrated that an appropriate combination of blood-based biomarkers could exhibit greater efficiency for cardiac rejection diagnosis. The combined detection of abnormal expression of miR-144-3p and miR-652-3p in the serum of ACR patients can improve the diagnostic sensitivity of rejection at an early stage and contribute to increasing the diagnostic accuracy, mainly in the lower rejection grades.

Mortality After the First Hospital Admission for Acute Heart Failure, De Novo Versus Acutely Decompensated Heart Failure With Reduced Ejection Fraction.

It is not clear to date whether a first admission in heart failure (HF) marks a worse evolution in patients not previously diagnosed with HF ("de novo HF") than those already diagnosed as outpatients ("acutely decompensated HF"). The aim of the study was to analyze whether survival in patients admitted for de novo HF differs from the survival in those admitted for a first episode of decompensation but with a previous diagnosis of HF. This study includes an analysis of 1,728 patients admitted for decompensated HF during 9 years. Readmissions and patients with left ventricular ejection fraction ≥50% were excluded (finally, 524 patients analyzed). We compared de novo HF (n = 186) in patients not diagnosed with HF, although their structural heart disease was defined, versus acutely decompensated HF (n = 338). The clinical profiles in both groups were similar. The de novo HF group more frequently presented with normal right ventricular function, with less presence of severe tricuspid regurgitation. The probability of survival was low in both groups. Thus, the median life in the de novo HF group was 2.1 years and in the acutely decompensated HF group, 3.5 years. There was a lower probability of long-term survival in the de novo HF group (p = 0.035). The variables associated with mortality were age (p <0.0001), ischemic heart disease (p <0.0001), hypertension (p = 0.009), obesity (p = 0.025), diabetes (p = 0.001), and N-terminal pro-brain natriuretic peptide at admission (p <0.0001). A higher glomerular filtration rate was associated with better survival (p = 0.033). De novo HF was associated with a higher mortality than chronic HF with acute decompensation (hazard ratio 1.53, 95% confidence interval 1.03 to 2.27, p = 0.036). In conclusion, the first admission for HF decompensation in patients with no previous diagnosis of HF identifies a subgroup of patients with higher long-term mortality.

Therapeutic approach in heart failure with poor diuretic response: peripheral ultrafiltration vs. conventional treatment.

AIMS: Patients with heart failure (HF) admitted for decompensation often require high doses of intravenous diuretics. This study aims to analyse whether the use of peripheral ultrafiltration (UF) in patients hospitalized for acute HF with systemic-predominant congestion results in better hydric control, renal protection, and reduction of hospital stay compared with conventional treatment. METHODS AND RESULTS: This study was a retrospective, comparative, single-centre study of 56 patients admitted for HF with systemic congestion with a poor diuretic response after diuretic escalation. One group underwent peripheral UF (35 patients) and others were maintained on intense diuretic treatment (control group, 21 patients). The diuretic response and days of hospital stay were compared between and within groups. The baseline characteristics of both groups were similar: males with right ventricular failure and renal dysfunction. The inter-group analysis showed that patients who received UF had better glomerular filtration rate (GFR; UF: 39.2 ± 18.2 vs. control: 28.7 ± 13.4 mL/min; P = 0.031) and higher diuresis (UF: 2184 ± 735 vs. control: 1335 ± 297 mL; P = 0.0001) at hospital discharge despite less need for diuretic drugs. Days of hospital stay were shorter in the UF group (UF: 11.7 ± 10.1 vs. control: 19.1 ± 14.4 days; P = 0.027). Intra-group analysis showed that patients receiving UF improved GFR, increased diuresis, and reduced weight at discharge (P < 0.001), whereas patients on conventional treatment only experienced improved weight but worsening renal function at discharge. CONCLUSIONS: In patients with acute HF with systemic congestion and diuretic resistance, UF compared with conventional treatment produces greater decongestion and renal protection, reduces the total diuretic load, and shortens the length of hospital stay.

[Usefulness of short-term peripheral ambulatory ultrafiltration in heart failure refractory to diuretics. Initial experience]. / Utilidad de la ultrafiltración ambulatoria de corta duración por vía periférica en insuficiencia cardíaca refractaria a diuréticos. Experiencia inicial.

INTRODUCTION AND OBJECTIVE: In heart failure congestion is the most common symptom and diuretic resistance is frequent. This study aims to analyse whether short-term peripheral outpatient ultrafiltration (UF) is useful and safe in these patients. MATERIAL AND METHODS: The first 5 patients ultrafiltrated for diuretic resistance in a fast-track unit of a referral hospital for 12hours were analysed. RESULTS: These patients were on treatment with at least 3 oral diuretics; UF made it possible to reduce and/or withdraw some of them. The volume extracted during the procedure was 1520±271ml. There were significant changes in diuresis (PreUF: 1360±164, PostUF: 1670±254ml; P=.035), weight (PreUF: 69.6±14, PostUF: 66.2±15kg; P=.0001) and creatinine (PreUF: 2.1±0.3, PostUF: 1.8±0.4mg; P= 0.023). CONCLUSIONS: In outpatients with heart failure and diuretic resistance, short-course peripheral UF was effective and safe.

Cardiac protein changes in ischaemic and dilated cardiomyopathy: a proteomic study of human left ventricular tissue.

The development of heart failure (HF) is characterized by progressive alteration of left ventricle structure and function. Previous works on proteomic analysis in cardiac tissue from patients with HF remain scant. The purpose of our study was to use a proteomic approach to investigate variations in protein expression of left ventricle tissue from patients with ischaemic (ICM) and dilated cardiomyopathy (DCM). Twenty-four explanted human hearts, 12 from patients with ICM and 12 with DCM undergoing cardiac transplantation and six non-diseased donor hearts (CNT) were analysed by 2DE. Proteins of interest were identified by mass spectrometry and validated by Western blotting and immunofluorescence. We encountered 35 differentially regulated spots in the comparison CNT versus ICM, 33 in CNT versus DCM, and 34 in ICM versus DCM. We identified glyceraldehyde 3-phophate dehydrogenase up-regulation in both ICM and DCM, and alpha-crystallin B down-regulation in both ICM and DCM. Heat shock 70 protein 1 was up-regulated only in ICM. Ten of the eleven differentially regulated proteins common to both aetiologies are interconnected as a part of a same network. In summary, we have shown by proteomics analysis that HF is associated with changes in proteins involved in the cellular stress response, respiratory chain and cardiac metabolism. Although we found altered expression of eleven proteins common to both ischaemic and dilated aetiology, we also observed different proteins altered in both groups. Furthermore, we obtained that seven of these eleven proteins are involved in cell death and apoptosis processes, and therefore in HF progression.