[Cardiovascular treatment in chronic kidney disease]. / Kardiovaskuläre Therapie bei chronischer Nierenerkrankung.

Patients with combined cardiac and renal diseases are particularly challenging in the routine clinical practice due to the substantial risk profile for increased morbidity and mortality. As cardiorenal patients have often been underrepresented in randomized, controlled interventional trials, guideline recommendations regarding the choice of treatment are often weaker for these individuals than for cardiovascular patients without chronic kidney disease. Furthermore, there are limitations in the approval of certain medications depending on the kidney function. This review addresses some considerations in crucial treatment areas for patients with cardiovascular diseases, whose treatment is significantly influenced by concomitant chronic kidney disease.

A prospective, randomized, controlled, multicentre trial for secondary prevention in patients with chronic coronary syndrome using a smartphone application for digital therapy: the CHANGE study protocol.

Aims: Coronary artery disease (CAD) remains the leading cause of death worldwide. 'Stable' CAD is a chronic progressive condition, which recent European guidelines recommend referring to as 'chronic coronary syndrome' (CCS). Despite therapeutic advances, morbidity and mortality among patients with CCS remain high. Optimal secondary prevention in patients with CCS includes optimization of modifiable risk factors with behavioural changes and pharmacological therapy. The CHANGE study aims to provide evidence for optimization of secondary prevention in CCS patients by using a smartphone application (app). Methods and results: The CHANGE study is designed as a prospective, randomized, controlled trial with a 1:1 allocation ratio, which is currently performed in nine centres in Germany in a parallel group design. 210 patients with CCS will be randomly allocated either to the control group (standard-of-care) or to the intervention group, who will be provided the VantisTherapy* app in addition to standard-of-care to incorporate secondary prevention into their daily life. The study will be performed in an open design. Outcomes will be assessed using objective data from three in-person visits (0, 12, and 24 weeks). Primary outcomes will involve adherence to secondary prevention recommendations and quality of life (QoL). The recruitment process started in July 2022. Conclusion: The CHANGE study will investigate whether a smartphone-guided secondary prevention app, combined with a monitor function compared with standard-of-care, has beneficial effects on overall adherence to secondary prevention guidelines and QoL in patients with CCS. Trial registration: The study is listed at the German study registry (DRKS) under the registered number DRKS00028081.

Inhibition of TRIF-Dependent Inflammation Decelerates Afterload-Induced Myocardial Remodeling.

Pressure-overload-induced cardiac hypertrophy represents one cause of the development of heart failure. The aim of this study is to characterize the influence of the TIR-domain-containing adapter-inducing interferon-ß (TRIF) during afterload-induced myocardial remodeling. After trans-aortic constriction (TAC), cardiac pressure overload leads to an early increase in MyD88- (Myeloid differentiation primary response gene 88) and TRIF-dependent cytokines. The maximum cytokine expression appeared within the first week and decreased to its control level within five weeks. While cardiomyocyte hypertrophy was comparable, the myocardial accumulation of the inflammatory cells was lower in TRIF-/-mice. At d7, TRIF deficiency reduced transcription factors and TRIF-dependent cytokines. Through the modulation of the TGF-ß-signaling pathway and anti-fibrotic microRNAs, TRIF was involved in the development of interstitial fibrosis. The absence of TRIF was associated with a decreased expression of proapoptotic proteins. In echocardiography and working heart analyses, TRIF deficiency slowed left-ventricular wall thickening, myocardial hypertrophy, and reduces the ejection fraction. In summary, TRIF is an important adapter protein for the release of inflammatory cytokines and the accumulation of inflammatory cells in the early stage of maladaptive cardiac remodeling. TRIF is involved in the development of cardiac fibrosis by modulating inflammatory and fibrotic signal transduction pathways.

[Update on PCSK9 inhibition]. / PCSK9-Hemmung ­ ein Update.

Lowering of low-density lipoprotein (LDL) cholesterol represents one of the most effective interventions in cardiovascular prevention. Besides the oral treatment with statins, ezetimibe and bempedoic acid, subcutaneously administered inhibitors of proprotein convertase subtilisin-kexin type 9 (PCSK9) have been established as further cornerstones of lipid-lowering treatment. The antibodies evolocumab and alirocumab are administered subcutaneously every 2-4 weeks and lower LDL cholesterol by around 60%, independent of pre-treatment with very good tolerability. Both drugs successfully reduced cardiovascular endpoints in large outcome trials. A novel principle of PCSK9 inhibition is RNA interference, which is exploited by the novel compound inclisiran. Inclisiran is a double-stranded modified RNA molecule, which neutralizes the mRNA of PCSK9 and thus inhibits PCSK9 protein synthesis intracellularly. Inclisiran only needs to be administered every 6 months. The cardiovascular outcome trial ORION­4 is currently ongoing. In Germany, prescription of PCSK9 inhibitors is regulated by the decision of the Federal Joint Committee. Novel strategies to inhibit PCSK9 function are under development and include orally available drugs and animal experiment concepts on gene editing, which are in different states of evaluation.

Plasma biomarkers outperform echocardiographic measurements for cardiovascular risk prediction in kidney transplant recipients: results of the HOME ALONE study.

Background: Since kidney transplant recipients (KTRs) have a high cardiovascular disease burden, adequate risk prediction is of importance. Whether echocardiographic parameters and plasma biomarkers, natriuretic peptides [N-terminal pro-B-type natriuretic peptide (NT-proBNP)] and troponin T provide complementary or overlapping prognostic information on cardiovascular events remains uncertain. Methods: The prospective Heterogeneity of Monocytes and Echocardiography Among Allograft Recipients in Nephrology (HOME ALONE) study followed 177 KTRs for 5.4 ± 1.7 years. Predefined endpoints were hospitalization for acute decompensated heart failure or all-cause death (HF/D) and major atherosclerotic cardiovascular events or all-cause death (MACE/D). At baseline, plasma NT-proBNP, plasma troponin T and echocardiographic parameters [left atrial volume index, left ventricular (LV) mass index, LV ejection fraction, and LV filling pressure] were assessed. Results: Among all echocardiographic and plasma biomarkers measured, only NT-proBNP was consistently associated with HF/D in univariate and multivariate {third versus first tertile: hazard ratio [HR] 4.20 [95% confidence interval (CI) 1.02-17.27]} analysis, and only troponin T was consistently associated with MACE/D in univariate and multivariate [third versus first tertile: HR 8.15 (95% CI 2.75-24.18)] analysis. Conclusion: Our data suggest that plasma biomarkers are robust and independent predictors of heart failure and atherosclerotic cardiovascular events after kidney transplantation, whereas standard echocardiographic follow-up does not add to risk prediction.

Chemokine CCL9 Is Upregulated Early in Chronic Kidney Disease and Counteracts Kidney Inflammation and Fibrosis.

Inflammation and fibrosis play an important pathophysiological role in chronic kidney disease (CKD), with pro-inflammatory mediators and leukocytes promoting organ damage with subsequent fibrosis. Since chemokines are the main regulators of leukocyte chemotaxis and tissue inflammation, we performed systemic chemokine profiling in early CKD in mice. This revealed (C-C motif) ligands 6 and 9 (CCL6 and CCL9) as the most upregulated chemokines, with significantly higher levels of both chemokines in blood (CCL6: 3-4 fold; CCL9: 3-5 fold) as well as kidney as confirmed by Enzyme-linked Immunosorbent Assay (ELISA) in two additional CKD models. Chemokine treatment in a mouse model of early adenine-induced CKD almost completely abolished the CKD-induced infiltration of macrophages and myeloid cells in the kidney without impact on circulating leukocyte numbers. The other way around, especially CCL9-blockade aggravated monocyte and macrophage accumulation in kidney during CKD development, without impact on the ratio of M1-to-M2 macrophages. In parallel, CCL9-blockade raised serum creatinine and urea levels as readouts of kidney dysfunction. It also exacerbated CKD-induced expression of collagen (3.2-fold) and the pro-inflammatory chemokines CCL2 (1.8-fold) and CCL3 (2.1-fold) in kidney. Altogether, this study reveals for the first time that chemokines CCL6 and CCL9 are upregulated early in experimental CKD, with CCL9-blockade during CKD initiation enhancing kidney inflammation and fibrosis.

Effects of selective heart rate reduction with ivabradine on LV function and central hemodynamics in patients with chronic coronary syndrome.

OBJECTIVES: We assessed left ventricular (LV) function and central hemodynamic effects in patients with a heart rate (HR) at rest of ≥70 beats per minute (bpm) and chronic coronary syndrome (CCS) after long-term treatment with ivabradine compared to placebo by cardiac magnetic resonance (CMR) imaging. METHODS AND RESULTS: In a randomized, double-blinded, prospective cross-over design, 23 patients (18 male, 5 female) were treated with ivabradine (7.5 mg bid) or placebo for 6 months. CMR imaging was performed at baseline and after 6 and 12 months to determine LV functional parameters.Mean resting HR on treatment with ivabradine was 58 ± 8.2 bpm and 70.2 ± 8.3 bpm during placebo (p < 0.0001).There was no difference in systolic LV ejection fraction (ivabradine 57.4 ± 11.2% vs placebo 53.0 ± 10.9%, p = 0.18), indexed end-diastolic (EDVi) or end-systolic volumes (ESVi). Indexed stroke volume (SVi) (ml/m2) remained unchanged after treatment with ivabradine. Volume time curve parameters reflecting systolic LV function (peak ejection rate and time) were unaffected by ivabradine, while both peak filling rate (PFR) and PFR/EDV were significantly increased. Mean aortic velocity (cm/s) was significantly reduced during treatment with ivabradine (ivabradine 6.7 ± 2.7 vs placebo 9.0 ± 3.4, p = 0.01). Aortic flow parameters were correlated to parameters of vascular stiffness. The strongest correlation was revealed for mean aortic velocity with aortic distensibility (AD) (r = -0.86 [-0.90 to -0.85], p < 0.0001). CONCLUSION: Long-term reduction of HR with ivabradine in patients with CCS improved diastolic function and reduced mean aortic flow velocity.

[Volume Management in Chronic kidney disease]. / Volumenmanagement bei chronischen Nierenerkrankungen.

Understanding the (patho-)physiology of volume regulation and osmoregulation is fundamental to guide patient advice and therapy in chronic kidney disease (CKD). Volume regulation primarily impacts the amount of sodium in the body, and it mainly affects the extracellular space, while osmoregulation primarily impacts the amount of free water, and it affects both the intra- and extracellular space. The kidneys control water and sodium homeostasis both through their sensor (e. g. tubuloglomerular feedback) and regulator systems (e. g. sodium reabsorption). Many CKD patients are advised by non-nephrologists to a high fluid intake, although they often do not require a daily intake of more than 1.5 litres. Many CKD patients are hypervolemic, and sodium restriction is of key importance in patients' effort to utilize lifestyle changes as therapeutic means. Pharmacologically, (particularly loop) diuretics are the basis of therapy, increasing sodium excretion. Recent developments shift the focus towards classes of drugs ameliorating prognosis in CKD: sodium-glucose linked transporter 2 (SGLT2) inhibitors have proven beneficial in heart and renal failure - by sodium and fluid excretion, among others; additionally, a novel mineralocorticoid receptor antagonist (MRA), finerenone, was recently shown to improve prognosis in CKD.

[SARS-CoV-2 vaccines - what the nephrologist should know]. / SARS-CoV-2-Impfungen ­ Was muss der Nephrologe wissen?

Only fifteen months after the beginning of the COVID-19 pandemic, several vaccines are already available for clinical use. While the spike protein of SARS-CoV-2 constitutes the main target of all predominant SARS-CoV-2 vaccines, they work by different mechanisms (mRNA-based vaccines vs. vector-based vaccines vs. protein-based vaccines).Though there are slight differences regarding the level of protection against mild COVID-19, all five vaccines that have been through phase 3 trials were nearly 100 % effective in preventing severe or fatal cases of COVID-19. The side effects were of short duration.Patients with chronic kidney disease (or other significant comorbidities) were largely excluded from Phase 3 trials, which makes definite recommendations concerning their vaccination difficult. The vaccine's effectiveness may be reduced in that population due to a uremic immune defect and/or immunosuppressive medication. However, these patients have an increased risk for severe or fatal COVID-19, so that they may particularly benefit from the vaccine.

Effects of edoxaban and warfarin on vascular remodeling: Atherosclerotic plaque progression and collateral artery growth.

BACKGROUND AND PURPOSE: Oral anticoagulation prevents thromboembolism in atrial fibrillation. Factor Xa inhibitors, like edoxaban, are known to reduce inflammation and proliferation of smooth muscle cells, while vitamin K antagonism can cause vascular calcific damage. The influence of edoxaban compared to warfarin on vascular remodeling, atherosclerosis and arteriogenesis is unknown. EXPERIMENTAL APPROACH: Apolipoprotein E knockout (ApoE -/-) mice were fed cholesterol-rich diet alone (control, co), with warfarin+vitamin K1 (warf) or with edoxaban (Edo) for 8 weeks. After 6 weeks, femoral artery ligation was performed. KEY RESULTS: There was no difference in hind-limb perfusion restoration between the three groups after 14 days (Co 0.36 ± 0.05 vs. Warf 0.39 ± 0.09 (p = .39), Co vs. Edo 0.51 ± 0.06 (p = .089), Warf vs. Edo (p = .83)) after ligation. Immuno-histologically, there was no difference in smooth muscle cell count in both hindlimbs between the three groups or in the amount of perivascular macrophages in collateral-bearing hindlimb tissue. Edoxaban showed the lowest amount of plaque tissue in the aortic sinus tissue (Co 74 ± 11% vs. Edo 62 ± 12% (p = .024), Co vs. Warf 69 ± 14% (p = .30), Edo vs. Warf (p = .14)) as well as the least amount of fibrosis (Co 3.1 ± 0.9% vs. Edo 1.7 ± 0.6% (p = .027), Co vs. Warf 4.1 ± 0.7% (p = .081), Edo vs. Warf (p < .001)). No difference in mRNA content of inflammatory cytokines in muscle tissue or spleen was detected between the three groups. CONCLUSION AND IMPLICATIONS: These data suggest that treatment with edoxaban unlike warfarin prevents vascular maladaptive remodeling, which may be clinically important.

[Anticoagulation and anti platelet therapy in patients with chronic kidney disease]. / Antikoagulation und Thrombozytenaggregationshemmung bei chronischer Nierenkrankheit.

Due to a high rate of cardiovascular events and the high-incidence of atrial fibrillation, many patients with chronic kidney disease (CKD) need to be anticoagulated and/or be subjected to anti platelet therapy (APT). As most studies historically excluded patients with CKD and a creatinine-clearance below 30 ml/min, guidelines for this patient group are only slowly being renewed depending on emerging study data.In patients with CKD stage 1-3, any non-vitamin K dependent oral anticoagulant (NOAC) should be preferentially used over vitamin K antagonists (VKA). In CKD stage 4, dabigatran should be avoided.The decision to anticoagulate a maintenance dialysis patient with atrial fibrillation has to be made on an individual basis considering their thrombosis and bleeding risk. Currently, in Europe all oral anticoagulants can be used only on an off-label basis in these patients. Randomized controlled trials investigating the efficacy and safety of apixaban versus VKA are currently underway. Alternative treatment options (e. g. left appendage occlusion) should be considered.Study data on APT in moderate to advanced CKD are similarly scarce. Despite APT not being renally eliminated, bleeding risk is increased due to uremic platelet dysfunction. When combining APT with NOAC, dose reduction of the latter needs to be addressed.

Effects of heart rate reduction with ivabradine on vascular stiffness and endothelial function in chronic stable coronary artery disease.

INTRODUCTION: Epidemiological and clinical studies have shown a relevant association between heart rate and cardiovascular mortality. Experimental studies identified vascular effects of heart rate reduction with the If channel inhibitor ivabradine. Therefore, the effects of heart rate reduction on endothelial function and indices of arterial stiffness were examined in patients with stable coronary artery disease in a prospective, placebo-controlled clinical crossover study. METHODS AND RESULTS: Twenty-three patients (18 men and 5 women) with a resting heart rate (HR) of at least 70 beats per minute (bpm) and stable coronary artery disease were enrolled in this study. In a cross-over design, all patients were treated with ivabradine (Iva, 7.5 mg b.i.d.) and placebo for 6 months each. Iva reduced heart rate by 11.4 bpm (Iva 58.8 ±â€Š8.2 bpm vs. placebo 70.2 ±â€Š8.3 bpm, P < 0.0001). Augmentation index (AIx75), carotid-femoral pulse wave velocity (cfPWV) and central aortic blood pressure were measured using applanation tonometry (SphygmoCor). HRR by Iva increased AIx75 by 12.4% (Iva 24.3 ±â€Š10.5% vs. placebo 21.3 ±â€Š10.1%, P < 0.05) and reduced cfPWV by 14.1% (Iva 6.3 ±â€Š1.7 m/s vs. placebo 7.3 ±â€Š1.4 m/s, P < 0.01). Iva increased mean central blood pressure by 7.8% (Iva 107.5 ±â€Š15.4 mmHg vs. placebo 99.1 ±â€Š12.2 mmHg, P < 0.001). Endothelial function was determined measuring the flow-mediated vasodilation (FMD) of the brachial artery. HRR by Iva increased FMD by 18.5% (Iva 7.3 ±â€Š2.2% vs. placebo 6.0 ±â€Š2.0%, P < 0.001). Aortic distensibility was characterized by MRI. HRR by Iva increased aortic distensibility by 33.3% (Iva 0.003 ±â€Š0.001/mmHg vs. placebo 0.002 ±â€Š0.010/mmHg, P < 0.01) and circumferential cyclic strain by 37.1% (Iva 0.062 ±â€Š0.027 vs. placebo 0.039 ±â€Š0.018, P < 0.0001). CONCLUSION: Heart rate reduction with Iva increased endothelium-dependent vasodilation and reduced arterial stiffness in patients with stable CAD. These findings corroborate and expand the results collected in experimental studies and indicate the importance of heart rate as a determinant of vascular function.

Echocardiographic criteria to detect unicuspid aortic valve morphology.

Aims: Unicuspid aortic valve (UAV) is a rare congenital malformation associated with severe aortic stenosis or regurgitation. This study aimed to systematically determine echocardiographic criteria to identify UAV. Methods and results: All patients underwent a preoperative baseline examination, including echocardiography. A total of 69 patients with intraoperatively confirmed UAV underwent an aortic valve repair procedure between August 2001 and May 2011. To compare the findings of UAV cases with those of other valve morphologies, we examined 99 consecutive patients with a bicuspid aortic valve (BAV) and 103 consecutive patients with a tricuspid aortic valve (TAV) undergoing isolated aortic valve surgery before May 2016. The mean age of the 271 patients was 44.2 ± 12.8 years; 85% were male, with a mean body mass index of 26.2 ± 4.0 kg/m2. Patients with UAV were younger and had fewer co-morbidities than patients with BAV or TAV, respectively. The major criteria for the echocardiographic diagnosis of UAV were defined based on our preoperative examination as follows: (i) single commissural attachment zone, (ii) rounded, leaflet-free edge on the opposite side of the commissural attachment zone, (iii) eccentric valvular orifice during systole, and (iv) patient age <20 years and mean transvalvular gradient >15 mmHg. The minor criteria were defined as an associated thoracic aortopathy and age <40 years. Three out of the four major criteria or two out of the four major criteria and one minor criterion were met in all patients with UAV and in none of the patients with BAV or TAV. Associated 95% confidence intervals were calculated for each estimate of sensitivity (94.7-100%) and specificity (98.1-100%), indicating that an adequate number of patients were included in each of the three groups. Conclusion: The proposed echocardiographic score appears to be a specific and sensitive method to distinguish UAV from BAV and TAV.

Interventional closure vs. medical therapy of patent foramen ovale for secondary prevention of stroke: updated meta-analysis.

BACKGROUND: We aimed to explore whether interventional closure of patent foramen ovale (PFO) results in reduction of composite outcome [stroke/transitory ischemic attack (TIA), death, and thrombolysis in myocardial infarction-TIMI bleeding], stroke and stroke/TIA compared to medical treatment in patients with cryptogenic stroke. METHODS AND RESULTS: Searching the PUBMED and Cochrane library database, we performed meta-analysis from all randomized controlled studies that compared effects of interventional PFO closure with medical treatment on stroke prevention. 3560 patients from six randomized trials were included. Interventional PFO closure reduced composite outcome (RR of 0.47, 0.26-0.85, p = 0.01), stroke (RR of 0.38, 0.18-0.82, p = 0.01) and stroke/TIA (RR of 0.56, 0.43-0.74, p < 0.0001). Analysis had 70.5% power to detect observed reduction of RR for the primary outcome, 70.6% for stroke and 98.7% for stroke/TIA. Bleeding rates were comparable (RR of 0.91, 0.60-1.38, p = 0.66), while there was higher burden of new AF (RR of 5.54, 3-10.2, p < 0.0001) after interventional closure. Subgroup analysis revealed that patients with large shunts had substantial less recurrent strokes over patients with small shunts (p for interaction = 0.02). Use of Amplatzer PFO device was associated with substantial less AF (RR of 2.36, p = 0.06) compared with other devices (RR of 8.93, p < 0.0001) (p for interaction = 0.04), with comparable benefit for stroke prevention (p for interaction = 0.73). CONCLUSIONS: Interventional closure of PFO resulted in significant reduction of stroke and stroke/TIA compared with antiplatelets/anticoagulants with comparable bleeding rates between the groups, whereas AF occurred more frequently in the intervention group. Patients with large shunts had more benefit from interventional closure.

Long-Term Hemodynamic Improvement after Transcatheter Mitral Valve Repair.

BACKGROUND: Correction of mitral regurgitation (MR) alters the load on the left ventricle. There are few data on the long-term hemodynamic adaptations of the cardiovascular system after transcatheter mitral valve repair (TMVR). The aim of this study was to determine a comprehensive hemodynamic status using noninvasive pressure-volume analysis. METHODS: Pressure-volume parameters were calculated from echocardiography with simultaneous arm-cuff blood pressure measurements at baseline before TMVR and 12 months after TMVR. Eighty-eight consecutive patients undergoing edge-to-edge mitral clip implantation because of grade 3+ or 4+, symptomatic (79.5% in New York Heart Association functional class ≥III) MR were prospectively enrolled. The mean left ventricular (LV) ejection fraction was 42 ± 14%. Sixty-seven percent of the patients had secondary MR. RESULTS: Twelve months after TMVR, 17.7% of patients had died, and 19.0% were rehospitalized because of decompensated heart failure. MR grade was ≤2+ in 90% of surviving patients, and 77% were in New York Heart Association functional class ≤II. LV end-diastolic volume index decreased from 87 ± 38 to 77 ± 40 mL/m2 (P < .0001), end-systolic volume index changed from 54 ± 34 to 50 ± 36 mL/m2 (P = .018), hence total stroke volume index was reduced (from 34 ± 11 to 28 ± 7 ml/m2, P < .0001). Ejection fraction and global longitudinal peak systolic strain remained unchanged. Increased forward ejection fraction (30 ± 14% vs 41 ± 20%, P < .0001), cardiac index (from 1.7 ± 0.4 to 1.9 ± 0.5 mL/min/m2, P = .003), and peak power index (214 ± 114 vs 280 ± 149 mm Hg/sec, P = .0001) as well as similar end-systolic elastance at reduced LV volumes indicated improved LV performance. Cardiac efficiency, measured as cardiac index relative to myocardial energy, was improved (0.012 ± 0.008 vs 0.019 ± 0.010 mm Hg-1, P = .002). Logistic regression analysis revealed baseline values of total ejection fraction and diastolic pulmonary pressure gradient as predictors of clinical improvement (odds ratios, 1.076 [P = .009] and 0.812 [P = .015], respectively) after TMVR. CONCLUSIONS: One year after TMVR, patients showed reverse remodeling and improved LV performance that was associated with improved symptom status. This hemodynamic improvement supports TMVR as long-term effective therapy for patients with symptomatic MR.

Oral Anticoagulation in Chronic Kidney Disease and Atrial Fibrillation.

BACKGROUND: Cardiological societies recommend, in their guidelines, that patients with atrial fibrillation and an intermediate (or higher) risk of stroke and systemic embolization should be treated with oral anticoagulant drugs. For patients who do not have mitral valve stenosis or a mechanical valve prosthesis, non-vitamin-K dependent oral anticoagulants (NOAC) are preferred over vitamin K antagonists (VKA) for this purpose. It is unclear, however, whether patients with chronic kidney disease and atrial fibrillation benefit from oral anticoagulation to the same extent as those with normal kidney function. It is also unclear which of the two types of anti - coagulant drug is preferable for patients with chronic kidney disease; NOAC are, in part, renally eliminated. METHODS: This review is based on pertinent publications retrieved by a selective literature search, and on international guidelines. RESULTS: Current evidence suggests that patients with atrial fibrillation who have chronic kidney disease with a glomerular filtration rate (GFR) above 15 mL/ min/1.73 m² should be treated with an oral anticoagulant drug if they have an at least intermediate risk of embolization, as assessed with the CHA2DS2-VASc score. For patients with advanced chronic kidney disease (GFR from 15 to 29 mL/ min/1.73 m²), however, this recommendation is based only on registry studies. For dialysis patients with atrial fibrillation, decisions whether to give oral anticoagulant drugs should be taken on an individual basis, in view of the elevated risk of hemorrhage and the unclear efficacy of such drugs in these patients. The subgroup analyses of the NOAC approval studies show that, for patients with atrial fibrillation and chronic kidney disease with a creatinine clearance of >25-30 mL/min, NOAC should be given in preference to VKA, as long as the patient does not have mitral valve stenosis or a mechanical valve prosthesis. For those whose creatinine clearance is less than 25 mL/min, the relative merits of NOAC versus VKA are still debated. CONCLUSION: The cardiological societies' recommendation that patients with atrial fibrillation should be given oral anticoagulant drugs applies to the majority of such patients who also have chronic kidney disease.

Mitral valve interventions in heart failure.

Secondary mitral regurgitation (MR) results from left ventricular dilatation and dysfunction. Quantification of secondary MR is challenging because of the underlying myocardial disease. Clinical and echocardiographic evaluation requires a multi-parametric approach. Severe secondary MR occurs in up to one-fourth of patients with heart failure with reduced ejection fraction, which is associated with a mortality rate of 40% to 50% in 3 years. Percutaneous edge-to-edge mitral valve repair (MitraClip) has emerged as an alternative to surgical valve repair to improve symptoms, functional capacity, heart failure hospitalizations, and cardiac haemodynamics. Further new transcatheter strategies addressing MR are evolving. The Carillion, Cardioband, and Mitralign devices were designed to reduce the annulus dilatation, which is a frequent and important determinant of secondary MR. Several transcatheter mitral valve replacement systems (Tendyne, CardiAQ-Edwards, Neovasc, Tiara, Intrepid, Caisson, HighLife, MValve System, and NCSI NaviGate Mitral) are emerging because valve replacement might be more durable compared with valve repair. In small studies, these interventional therapies demonstrated feasibility and efficiency to reduce MR and to improve heart failure symptoms. However, neither transcatheter nor surgical mitral valve repair or replacement has been proven to impact on the prognosis of heart failure patients with severe MR, which remains high with a mortality rate of 14-20% at 1 year. To date, the primary indication for treatment of secondary severe MR is the amelioration of symptoms, reinforcing the value of a Heart Team discussion. Randomized studies to investigate the treatment effect and long-term outcome for any transcatheter or surgical mitral valve intervention compared with optimized medical treatment are urgently needed and underway.