The RNA-binding protein HuR is essential for the B cell antibody response.

Post-transcriptional regulation of mRNA by the RNA-binding protein HuR (encoded by Elavl1) is required in B cells for the germinal center reaction and for the production of class-switched antibodies in response to thymus-independent antigens. Transcriptome-wide examination of RNA isoforms and their abundance and translation in HuR-deficient B cells, together with direct measurements of HuR-RNA interactions, revealed that HuR-dependent splicing of mRNA affected hundreds of transcripts, including that encoding dihydrolipoamide S-succinyltransferase (Dlst), a subunit of the 2-oxoglutarate dehydrogenase (α-KGDH) complex. In the absence of HuR, defective mitochondrial metabolism resulted in large amounts of reactive oxygen species and B cell death. Our study shows how post-transcriptional processes control the balance of energy metabolism required for the proliferation and differentiation of B cells.

Fewer Worsening Heart Failure Events With HeartLogic on top of Standard Care: a Propensity-Matched Cohort Analysis.

BACKGROUND: The implantable cardiac defibrillator-based HeartLogic algorithm aims to detect impending fluid retention in patients with heart failure (HF). Studies show that HeartLogic is safe to integrate into clinical practice. The current study investigates whether HeartLogic provides clinical benefit on top of standard care and device telemonitoring in patients with HF. METHODS: A multicenter, retrospective, propensity-matched cohort analysis was performed in patients with HF and implantable cardiac defibrillators, and it compared HeartLogic to conventional telemonitoring. The primary endpoint was the number of worsening HF events. Hospitalizations and ambulatory visits due to HF were also evaluated. RESULTS: Propensity score matching yielded 127 pairs (median age 68 years, 80% male). Worsening HF events occurred more frequently in the control group (2; IQR 0-4) compared to the HeartLogic group (1; IQR 0-3; P = 0.004). The number of HF hospitalization days was higher in controls than in the HeartLogic group (8; IQR 5-12 vs 5; IQR 2-7; P = 0.023), and ambulatory visits for diuretic escalation were more frequent in the control group than in the HeartLogic group (2; IQR 0-3 vs 1; IQR 0-2; P = 0.0001). CONCLUSION: Integrating the HeartLogic algorithm in a well-equipped HF care path on top of standard care is associated with fewer worsening HF events and shorter duration of fluid retention-related hospitalizations.

Clinical inertia in the treatment of heart failure: a major issue to tackle.

Despite an enormous improvement in heart failure management during the last decades, the hospitalization and mortality rate of heart failure patients still remain very high. Clinical inertia, defined as the lack of treatment intensification in a patient not at evidence-based goals for care, is an important underlying cause. Clinical inertia is extensively described in hypertension and type 2 diabetes mellitus, but increasingly recognized in heart failure as well. Given the well-established guidelines for the management of heart failure, these are still not being reflected in clinical practice. While the absolute majority of patients were treated by guideline-directed heart failure drugs, only a small percentage of these patients reached the correct guideline-recommended target dose of angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, beta-blockers, mineralocorticoid receptor antagonists, and angiotensin receptor-neprilysin inhibitors. This considerable under-treatment leads to a large number of avoidable hospitalizations and deaths. This review discusses clinical inertia in heart failure and explains its major contributing factors (i.e., physician, patient, and system) and touches upon some recommendations to prevent clinical inertia and ameliorate heart failure treatment.

Inhibition of MicroRNA-146a and Overexpression of Its Target Dihydrolipoyl Succinyltransferase Protect Against Pressure Overload-Induced Cardiac Hypertrophy and Dysfunction.

BACKGROUND: Cardiovascular diseases remain the predominant cause of death worldwide, with the prevalence of heart failure continuing to increase. Despite increased knowledge of the metabolic alterations that occur in heart failure, novel therapies to treat the observed metabolic disturbances are still lacking. METHODS: Mice were subjected to pressure overload by means of angiotensin-II infusion or transversal aortic constriction. MicroRNA-146a was either genetically or pharmacologically knocked out or genetically overexpressed in cardiomyocytes. Furthermore, overexpression of dihydrolipoyl succinyltransferase (DLST) in the murine heart was performed by means of an adeno-associated virus. RESULTS: MicroRNA-146a was upregulated in whole heart tissue in multiple murine pressure overload models. Also, microRNA-146a levels were moderately increased in left ventricular biopsies of patients with aortic stenosis. Overexpression of microRNA-146a in cardiomyocytes provoked cardiac hypertrophy and left ventricular dysfunction in vivo, whereas genetic knockdown or pharmacological blockade of microRNA-146a blunted the hypertrophic response and attenuated cardiac dysfunction in vivo. Mechanistically, microRNA-146a reduced its target DLST-the E2 subcomponent of the α-ketoglutarate dehydrogenase complex, a rate-controlling tricarboxylic acid cycle enzyme. DLST protein levels significantly decreased on pressure overload in wild-type mice, paralleling a decreased oxidative metabolism, whereas DLST protein levels and hence oxidative metabolism were partially maintained in microRNA-146a knockout mice. Moreover, overexpression of DLST in wild-type mice protected against cardiac hypertrophy and dysfunction in vivo. CONCLUSIONS: Altogether we show that the microRNA-146a and its target DLST are important metabolic players in left ventricular dysfunction.

Adherence, knowledge, and perception about oral anticoagulants in patients with atrial fibrillation at high risk for thromboembolic events after radiofrequency ablation.

AIMS: This study aimed to: (a) determine adherence rates to oral anticoagulants in atrial fibrillation patients with a high risk for thromboembolic events postradiofrequency ablation; (b) evaluate patients' knowledge and perceptions towards oral anticoagulants; and (c) explore the impact of patients' knowledge and perceptions on treatment adherence. BACKGROUND: Atrial fibrillation is a common arrhythmia associated with an increased risk of developing thromboembolic events such as stroke. Although adherence to oral anticoagulants is crucial to prevent such complications, the relationship between adherence, knowledge and patient perceptions is poorly understood in patients with atrial fibrillation at high risk for thromboembolic events after radiofrequency ablation. DESIGN: A cross-sectional observational survey study was performed in a single centre. METHODS: The levels of adherence, knowledge, and perception towards oral anticoagulants were assessed using the 8-item Morisky Medication Adherence Scale, Knowledge of Oral Anticoagulation Tool, Perception of Anticoagulant Treatment Questionnaire and Benefit-Risk Perception Tool, respectively. Results from these self-reported tools were analysed descriptively. A multivariable binary logistic regression model was used to identify factors associated with levels of adequate adherence. RESULTS: Adequate treatment adherence was found in three-quarters of patients. The total mean knowledge score was low. Participants expressed high ease of use and low burden of treatment. Higher total knowledge and satisfaction scores were significant factors associated with higher levels of adherence. CONCLUSION: There remains a huge unmet need to follow-up and educate patients with atrial fibrillation, focusing on good knowledge and correct perception of the advantages and disadvantages of oral anticoagulants. Our results suggest that increased knowledge and satisfaction rates might have a positive impact on adherence to oral anticoagulants.

Should MRAs be at the front row in heart failure? A plea for the early use of mineralocorticoid receptor antagonists in medical therapy for heart failure based on clinical experience.

The brand new 2016 ESC guidelines for the treatment of acute and chronic heart failure continue to give a prominent place to mineralocorticoid receptor antagonists in the treatment of chronic heart failure with reduced ejection fraction (HFrEF). In the prevention of HF hospitalization and death, a class I, level of recommendation A, is given to MRAs for patients with HFrEF, who remain symptomatic despite treatment with an ACE-inhibitor and a beta-blocker and have an LVEF below 35 %. This recommendation is primarily based on two landmark trials, the RALES trial (for spironolactone) and the EMPHASIS-HF trial (for eplerenone). A crucial question is, however, why MRAs are advised only in "third place," i.e., after optimal up-titration of ACE-inhibitors and beta-blockers. We wonder whether MRAs could not or should not be given earlier in the treatment of HFrEF, namely before or together with the up-titration of ACE-inhibitors and beta-blockers. Several arguments to support this plea are described in this short paper.

Leptin-adiponectin ratio in pre-diabetic patients undergoing percutaneous coronary intervention.

BACKGROUND: The obesity-related hormones leptin and adiponectin are independently and oppositely associated with insulin resistance, which is an important risk factor for coronary artery disease (CAD) and restenosis after coronary intervention. In this report, we set out to determine the role of the leptin-adiponectin ratio (LAR) in non-diabetic patients with or without impaired glucose tolerance undergoing a percutaneous coronary intervention. METHODS: 300 PCI patients were enrolled in this prospective single-centre study. Patients with known diagnosis of diabetes (n = 50) and newly diagnosed diabetes (2h OGTT > 200 mg/dL, n = 25) were excluded. In both stable and acute subjects, assessment was done on the day of discharge and included a fasting glucose level, leptin, adiponectin and an oral glucose tolerance test (OGTT). RESULTS: LAR was significantly higher in diabetic (7.2 ± 0.7) than in non-diabetic patients (3.9 ± 0.3, P = 0.001), and even higher in newly diagnosed diabetics (9.8 ± 1.5, P < 0.001). Likewise, among non-diabetic patients, LAR was significantly higher in patients with impaired glucose tolerance. LAR was significantly higher in pre-diabetic (4.57 ± 0.48) versus normoglycaemic patients (3.45 ± 0.33, P = 0.05). LAR was found to be numerically higher in pre-diabetic versus normoglycaemic patients with two- and three-vessel disease (VD), but not in patients with single VD. In pre-diabetic patients, LAR was found to be significantly increased with more advanced CAD (P = 0.021), independent of stable versus unstable presentation. CONCLUSIONS: LAR is related to the extent of CAD in pre-diabetic patients but not in normoglycaemic patients. This finding might in part explain the poorer outcome in revascularized patients with impaired glucose tolerance compared to normoglycaemic patients.

Implementation of guideline-directed medical therapy for heart failure patients with reduced ejection fraction in Belgium: a Delphi panel approach.

BACKGROUND: The 2021 European Society of Cardiology (ESC) guidelines recommended a shift from a traditional hierarchical treatment for heart failure with reduced ejection fraction (HFrEF) to a four-pillar medical therapy strategy intended for near-simultaneous initiation. However, practical guidance for implementation in clinical practice is lacking. To address this, a Delphi Panel of 12 Belgian heart failure experts aimed to obtain consensus on integrating guideline-directed medical therapy (GDMT) in HFrEF patients in Belgian clinical practice, considering local specificities, including reimbursement criteria. METHODS: A geographically representative sample of 12 Belgian cardiologists engaged in a three-round Delphi process, evolving from 20 open-ended questions to 39 statements. A qualitative analysis after the first round resulted in expert statements for the subsequent questionnaire, categorised into treatment for newly diagnosed and chronic HFrEF patients. RESULTS: The Delphi consensus revealed four key findings: (i) Agreement on initiating the four medical cornerstones within 7-14 days of HFrEF diagnosis, prioritising initiation over individual class up-titration; (ii) Lack of consensus on a fixed sequence for initiation due to patient variability and national reimbursement criteria; (iii) Emphasis on treatment adjustment based on the patient's clinical presentation and comorbidities; (iv) Recognition of the crucial role of regular follow-up visits, allowing optimisation of medical therapy where appropriate. CONCLUSION: This national Delphi consensus addresses clinical implementation of GDMT in HFrEF patients for Belgian cardiologists. The consensus highlights the importance of swift implementation of the four cornerstone medical therapies in newly diagnosed HFrEF patients, individualising treatment sequencing, and ensuring regular follow-up to optimise therapy.

CIED-based remote monitoring in heart failure using the HeartLogic™ algorithm: Which patients benefit most?

BACKGROUND & AIMS: Early identification of worsening HF enables timely adjustments to prevent hospitalization. Recent studies show the HeartLogic™ algorithm detects congestion and reduces HF events. However, it is unclear which patients benefit most. Therefore, this study aims to identify and characterize HF patients who benefit most from CIED-based remote monitoring with HeartLogic™. METHODS: In this multicenter retrospective study, patients with a CIED and HeartLogic™ algorithm under structured follow-up were included. Patients were classified as having "substantial benefit" or "no benefit" from monitoring. RESULTS: In total, 242 patients were included (male n = 190, 79%, median age 61 years [IQR 61-77]). Median follow-up was 1.2 years [IQR 1.1-2.7]. Among 378 alerts, 266 were true positive (70%) and 112 false positive (30%). Of the 242 patients, 69 (29%) were classified as having "substantial benefit", while 173 (71%) had "no benefit" from HeartLogic™ monitoring. Univariate and multivariate analysis showed that patients with "substantial benefit" had higher NYHA functional class (OR 2.64, P = 0.004), higher NT-ProBNP (OR 1.02, P = 0.003), higher serum creatinine (OR 1.10, P < 0.001), lower LVEF (OR 1.19, P = 0.004), more severe mitral regurgitation (OR 2.16, P = 0.006), higher right ventricular end diastolic volume (OR 1.05, P = 0.040), higher pulmonary artery pressures (OR 1.19, P = 0.003), and were more likely to use loop diuretics (OR 2.79, P = 0.001). Among patients with "substantial benefit," the positive predictive value (PPV) of HeartLogic™ to detect congestion was 92%. CONCLUSION: The utilization of CIED-based HeartLogic™ driven HF care demonstrated pronounced efficacy, predominantly in patients exhibiting characteristics of HF at a more advanced disease stage.

Differential expression of epigenetic modifiers in early and late cardiotoxic heart failure reveals DNA methylation as a key regulator of cardiotoxicity.

Background: Anthracycline-induced cardiotoxicity is a well-known serious clinical entity. However, detailed mechanistic insights on how short-term administration leads to late and long-lasting cardiotoxicity, are still largely undiscovered. We hypothesize that chemotherapy provokes a memory effect at the level of epigenomic DNA modifications which subsequently lead to cardiotoxicity even years after cessation of chemotherapy. Methods: We explored the temporal evolution of epigenetic modifiers in early and late cardiotoxicity due to anthracyclines by means of RNA-sequencing of human endomyocardial left ventricular biopsies and mass spectrometry of genomic DNA. Based on these findings, validation of differentially regulated genes was obtained by performing RT-qPCR. Finally, a proof-of-concept in vitro mechanistic study was performed to dissect some of the mechanistic aspects of epigenetic memory in anthracycline-induced cardiotoxicity. Results: Correlation of gene expression between late and early onset cardiotoxicity revealed an R 2 value of 0.98, demonstrating a total of 369 differentially expressed genes (DEGs, FDR < 0.05). of which 72% (n = 266) were upregulated, and 28% of genes, (n = 103) downregulated in later as compared to earlier onset cardiotoxicity. Gene ontology analysis showed significant enrichment of genes involved in methyl-CpG DNA binding, chromatin remodeling and regulation of transcription and positive regulation of apoptosis. Differential mRNA expression of genes involved in DNA methylation metabolism were confirmed by RT-qPCR in endomyocardial biopsies. In a larger biopsy cohort, it was shown that Tet2 was more abundantly expressed in cardiotoxicity biopsies vs. control biopsies and vs. non-ischemic cardiomyopathy patients. Moreover, an in vitro study was performed: following short-term doxorubicin treatment, H9c2 cells were cultured and passaged once they reached a confluency of 70%-80%. When compared to vehicle-only treated cells, in doxorubicin-treated cells, three weeks after short term treatment, Nppa, Nppb, Tet1/2 and other genes involved in active DNA demethylation were markedly upregulated. These alterations coincided with a loss of DNA methylation and a gain in hydroxymethylation, reflecting the epigenetic changes seen in the endomyocardial biopsies. Conclusions: Short-term administration of anthracyclines provokes long-lasting epigenetic modifications in cardiomyocytes both in vivo and in vitro, which explain in part the time lapse between the use of chemotherapy and the development of cardiotoxicity and, eventually, heart failure.

Serial Non-Invasive Myocardial Work Measurements for Patient Risk Stratification and Early Detection of Cancer Therapeutics-Related Cardiac Dysfunction in Breast Cancer Patients: A Single-Centre Observational Study.

Serial transthoracic echocardiographic (TTE) assessment of LVEF and GLS are the gold standard in screening Cancer Therapeutics-Related Cardiac Dysfunction (CTRCD). Non-invasive left-ventricle (LV) pressure-strain loop (PSL) emerged as a novel method to quantify Myocardial Work (MW). This study aims to describe the temporal changes and longitudinal trajectories of MW indices during cardiotoxic treatment. We included 50 breast cancer patients with normal LV function referred for anthracycline therapy w/wo Trastuzumab. Medical therapy, clinical and echocardiographic data were recorded before and 3, 6, and 12 months after initiation of the chemotherapy. MW indices were calculated through PSL analysis. According to ESC guidelines, mild and moderated CTRCD was detected in 10 and 9 patients, respectively (20% CTRCDmild, 18% CTRCDmod), while 31 patients remained free of CTRCD (62% CTRCDneg). Prior to chemotherapy MWI, MWE and CW were significantly lower in CTRCDmod than in CTRCDneg and CTRCDmild. Overt cardiac dysfunction in CTRCDmod at 6 months was accompanied by significant worse values in MWI, MWE and WW compared to CTRCDneg and CTRCDmild. MW features such as low baseline CW, especially when associated with a rise in WW at follow-up, may identify patients at risk for CTRCD. Additional studies are needed to explore the role of MW in CRTCD.

The in- and out-of-hospital management of HF patients: results from a nationwide Belgian survey.

BACKGROUND: We conducted a nationwide survey to describe the in-and out-of-hospital flow (diagnosis, treatment and follow-up) of patients with heart failure with reduced ejection fraction (HFrEF). METHOD: A survey was developed with five dedicated HF cardiologists. The data are all self-reported by cardiologists. RESULTS: The response rate was 84%. Presence of a dedicated HF cardiologist or HF nurse was indicated by 49% and 46% of the hospitals respectively. Devices (p < .05), angiotensin receptor neprilysin inhibitors, and rehabilitation are considered more standard of care therapy by dedicated compared to non-dedicated HF cardiologists. Most cardiologists indicated that target dosages of HF drugs can be reached in 25‒75% of patients. Achieving >75% of the target dose seems easier for angiotensin converting enzyme inhibitor/angiotensin receptor blockers (ACEI/ARB) (22%) and mineralocorticoid receptor antagonists (25%), compared to ß-blockers (10%) and angiotensin receptor neprilysin inhibitors (7%). 62%, 49% and 4% of the cardiologists indicated to use subtypes of angiotensin converting enzyme inhibitors, angiotensin receptor blockers and ß-blockers respectively not validated in the HF population. In the acute setting, dedicated HF cardiologists (23%) are less influenced by blood parameters for decongestion compared to non-dedicated HF cardiologists (39%). They tend to change patients more to guideline-recommended drugs (60% vs 47%). Six minutes walk test and ergospirometry are significantly more used by dedicated compared to non-dedicated HF cardiologists for HF drug change (17% and 29% vs 2% and 4%). CONCLUSION: This survey showed that a minority of hospitals have HF care. Those that do, report a higher implementation of guideline-recommended diagnosis, treatment and follow-up of HF patients. Competent authorities could use this survey as a tool to improve HF care.

Clinical and economic impact of HeartLogic™ compared with standard care in heart failure patients.

AIMS: The implantable cardiac defibrillator/cardiac resynchronization therapy with defibrillator-based HeartLogic™ algorithm has recently been developed for early detection of impending decompensation in heart failure (HF) patients; but whether this novel algorithm can reduce HF hospitalizations has not been evaluated. We investigated if activation of the HeartLogic algorithm reduces the number of hospital admissions for decompensated HF in a 1 year post-activation period as compared with a 1 year pre-activation period. METHODS AND RESULTS: Heart failure patients with an implantable cardiac defibrillator/cardiac resynchronization therapy with defibrillator with the ability to activate HeartLogic and willingness to have remote device monitoring were included in this multicentre non-blinded single-arm trial with historical comparison. After a HeartLogic alert, the presence of HF symptoms and signs was evaluated. If there were two or more symptoms and signs apart from the HeartLogic alert, lifestyle advices were given and/or medication was adjusted. After activation of the algorithm, patients were followed for 1 year. HF events occurring in the 1 year prior to activation and in the 1 year after activation were compared. Of the 74 eligible patients (67.2 ± 10.3 years, 84% male), 68 patients completed the 1 year follow-up period. The total number of HF hospitalizations reduced from 27 in the pre-activation period to 7 in the post-activation period (P = 0.003). The number of patients hospitalized for HF declined from 21 to 7 (P = 0.005), and the hospitalization length of stay diminished from average 16 to 7 days (P = 0.079). Subgroup analysis showed similar results (P = 0.888) for patients receiving cardiac resynchronization therapy during the pre-activation period or not receiving cardiac resynchronization therapy, meaning that the effect of hospitalizations cannot solely be attributed to reverse remodelling. Subanalysis of a single-centre Belgian subpopulation showed important reductions in overall health economic costs (P = 0.025). CONCLUSION: Activation of the HeartLogic algorithm enables remote monitoring of HF patients, coincides with a significant reduction in hospitalizations for decompensated HF, and results in health economic benefits.

Low MicroRNA-126 Levels in Right Ventricular Endomyocardial Biopsies Coincide With Cardiac Allograft Vasculopathy in Heart Transplant Patients.

Endothelium-enriched microRNAs (miRs) are involved in the development of cardiac allograft vasculopathy (CAV). Recently, serum-derived miR-126-3p and -5p, known endothelial microRNAs with a crucial function in angiogenesis and re-endothelialization, provided additional predictive power for cardiac allograft vasculopathy in addition to clinical predictors. However, their myocardial expression in and relationship with CAV are still unknown. Our study aim was to investigate the expression of endomyocardial microRNA-126-3p and microRNA-126-5p levels in heart transplant recipients and their relationship with allograft vasculopathy. METHODS: We studied 39 heart transplant recipients, 21 with proven allograft vasculopathy (CAV+) and 18 without allograft vasculopathy (CAV-) with serial coronary angiograms. Additionally, 8 patients with end-stage native coronary artery disease (CAD) were added to the study to investigate disease specificity of the microRNA signature. The mRNA levels of miR-126-3p and miR-126-5p were determined by qRT-PCR in the right ventricular endomyocardial biopsies obtained at baseline and during routine follow-up. RESULTS: MiR-126-3p levels were significantly lower in the CAV+ group compared to the CAV- group at follow-up, while miR-126-5p levels were unaltered. This was in stark contrast to native CAD patients in whom miR-126-3p and -5p levels were significantly higher. qPCR levels of miR-126 targets are differentially regulated in CAV versus ischemic cardiomyopathy and are influenced by the administration of immunosuppressive agents in endothelial cells. CONCLUSIONS: Our data provide evidence for a distinct microRNA signature in heart transplantation patients with allograft vasculopathy. In contrast to CAD patients, lower miR-126-3p levels coincide with the development of cardiac allograft vasculopathy. Further studies in a larger patient population are warranted to determine if the serial measurement of myocardial microRNA-126 products could help in risk assessment and early detection of CAV.

Technology Advances to Improve Response to Cardiac Resynchronization Therapy: What Clinicians Should Know.

Cardiac resynchronization therapy (CRT) is a well-established treatment for symptomatic heart failure patients with reduced left ventricular ejection fraction, prolonged QRS duration, and abnormal QRS morphology. The ultimate goals of modern CRT are to improve the proportion of patients responding to CRT and to maximize the response to CRT in patients who do respond. While the rate of CRT nonresponders has moderately but progressively decreased over the last 20 years, mostly in patients with left bundle branch block, in patients without left bundle branch block the response rate is almost unchanged. A number of technological advances have already contributed to achieve some of the objectives of modern CRT. They include novel lead design (the left ventricular quadripolar lead, and multipoint pacing), or the possibility to go beyond conventional delivery of CRT (left ventricular endocardial pacing, His bundle pacing). Furthermore, to improve CRT response, a triad of actions is paramount: reducing the burden of atrial fibrillation, reducing the number of appropriate and inappropriate interventions, and adequately predicting heart failure episodes. As in other fields of cardiology, technology and innovations for CRT delivery have been at the forefront in transforming-improving-patient care; therefore, these innovations are discussed in this review.

Clinical case report: a rare cause of acute kidney failure - tissue is the issue.

A patient was admitted to the medical emergency department by his family physician. His complaints were weakness and fatigue for more than one week. Four days before admission, he went to his general practitioner for these complaints and also for painful elbows. His physician prescribed diclofenac and esomeprazole. Upon presentation, he had high systolic/diastolic blood pressure (>180/>90 mm Hg, measured repeatedly), and otherwise normal parameters. He had gained 6.5 kg in body weight. Clinical examination was normal, except for very mild bilateral malleolar edema. Routine blood tests showed a strongly elevated serum creatinine, hyperkalemia, and elevated lactate dehydrogenase. Haptoglobin levels were normal. Urinalysis showed a normal sediment, urine and blood cultures remained sterile. Ophthalmoscopy was completely normal, as was a routine chest X-ray. Renal ultrasound demonstrated kidneys with a diameter of 13 cm. Due to uncontrollable hypertension, our patient was hospitalized at the intensive care department where intravenous nifedipine was started, with good instantaneous control of blood pressure. Because of increasing potassium levels acute hemodialysis was started within 24 h after admission. Differential diagnosis consisted of diclofenac- or esomeprazole-induced interstitial nephritis or rapidly progressive glomerulonephritis. A renal biopsy was performed within 72 h after admission. The kidney biopsy showed an overwhelming inflammatory cell infiltrate consisting of a monoclonal lymphocytic cell population. However, the numerous mitotic figures, polyploidy, and prominent nucleoli present, were indicative of a lymphoma. Additional stainings confirmed a non-Hodgkin diffuse large-cell B-cell lymphoma. Treatment with R-CHOP (rituximab, cyclophosphamide, doxorubicine, vincristine, and prednisolone) was initiated with very good clinical and biochemical response, yet only mild recovery of kidney function. Occasionally the kidney is involved as an extranodal non-Hodgkin lymphoma (NHL) localization. However, a primary presentation of acute kidney failure due to lymphoma localization is extremely rare. Our case demonstrates that early renal biopsy is indispensable for fast and adequate diagnosis and treatment.

Metabolic support for the heart: complementary therapy for heart failure?

The failing heart has an increased metabolic demand and at the same time suffers from impaired energy efficiency, which is a detrimental combination. Therefore, therapies targeting the energy-deprived failing heart and rewiring cardiac metabolism are of great potential, but are lacking in daily clinical practice. Metabolic impairment in heart failure patients has been well characterized for patients with reduced ejection fraction, and is coming of age in patients with 'preserved' ejection fraction. Targeting cardiomyocyte metabolism in heart failure could complement current heart failure treatments that do improve cardiovascular haemodynamics, but not the energetic status of the heart. In this review, we discuss the hallmarks of normal cardiac metabolism, typical metabolic disturbances in heart failure, and past and present therapeutic targets that impact on cardiac metabolism.

Avances tecnológicos para mejorar la respuesta ventricular en la resincronización cardiaca: lo que el clínico debe conoce / Technology advances to improve response to cardiac resynchronization therapy: what clinicians should know

La terapia de resincronización cardiaca (TRC) es un tratamiento establecido para los pacientes con insuficiencia cardiaca, fracción de eyección reducida y con intervalo QRS ancho El objetivo actual de la TRC es «incrementar la tasa de pacientes respondedores a la resincronización». Si bien la tasa de no respondedores a la TRC ha ido decreciendo en los últimos 20 años, sobre todo en los pacientes con bloqueo de rama izquierda, en aquellos pacientes sin bloqueo de rama izquierda dicha tasa se ha mantenido inalterada. Ciertos avances tecnológicos recientes han contribuido a aumentar la tasa de respondedores a la TRC. Entre ellos los nuevos diseños de los cables (cable cuadripolar de ventrículo izquierdo con estimulación en varios puntos), o la posibilidad de ir más allá de la TRC convencional (estimulación endocárdica en ventrículo izquierdo, estimulación del haz de His). Además, para mejorar la tasa de respondedores, se tienen que abordar 3 aspectos: reducir la carga de fibrilación auricular, reducir el número de intervenciones apropiadas e inapropiadas y predecir con precisión los episodios de insuficiencia cardiaca. En esta revisión se presentan las últimas innovaciones tecnológicas en la TRC, las cuales prentenden transformar (mejorar), como en otras áreas de la cardiología, el manejo y cuidado de los pacientes

Cardiac resynchronization therapy (CRT) is a well-established treatment for symptomatic heart failure patients with reduced left ventricular ejection fraction, prolonged QRS duration, and abnormal QRS morphology. The ultimate goals of modern CRT are to improve the proportion of patients responding to CRT and to maximize the response to CRT in patients who do respond. While the rate of CRT nonresponders has moderately but progressively decreased over the last 20 years, mostly in patients with left bundle branch block, in patients without left bundle branch block the response rate is almost unchanged. A number of technological advances have already contributed to achieve some of the objectives of modern CRT. They include novel lead design (the left ventricular quadripolar lead, and multipoint pacing), or the possibility to go beyond conventional delivery of CRT (left ventricular endocardial pacing, His bundle pacing). Furthermore, to improve CRT response, a triad of actions is paramount: reducing the burden of atrial fibrillation, reducing the number of appropriate and inappropriate interventions, and adequately predicting heart failure episodes. As in other fields of cardiology, technology and innovations for CRT delivery have been at the forefront in transforming-improving-patient care; therefore, these innovations are discussed in this review