Nikolaj Ihlemann

Transcatheter Versus Surgical Aortic Valve Replacement in Patients With Severe Aortic Valve Stenosis 1-Year Results From the All-Comers NOTION Randomized Clinical Trial

BACKGROUND Transcatheter aortic valve replacement (TAVR) is an option in certain high-risk surgical patients with severe aortic valve stenosis. It is unknown whether TAVR can be safely introduced to lower-risk patients. OBJECTIVES The NOTION (Nordic Aortic Valve Intervention Trial) randomized clinical trial compared TAVR with surgical aortic valve replacement (SAVR) in an all-comers patient cohort. METHODS Patients ≥ 70 years old with severe aortic valve stenosis and no significant coronary artery disease were randomized 1:1 to TAVR using a self-expanding bioprosthesis versus SAVR. The primary outcome was the composite rate of death from any cause, stroke, or myocardial infarction (MI) at 1 year. RESULTS A total of 280 patients were randomized at 3 Nordic centers. Mean age was 79.1 years, and 81.8% were considered low-risk patients. In the intention-to-treat population, no significant difference in the primary endpoint was found (13.1% vs. 16.3%; p = 0.43 for superiority). The result did not change in the as-treated population. No difference in the rate of cardiovascular death or prosthesis reintervention was found. Compared with SAVR-treated patients, TAVR-treated patients had more conduction abnormalities requiring pacemaker implantation, larger improvement in effective orifice area, more total aortic valve regurgitation, and higher New York Heart Association functional class at 1 year. SAVR-treated patients had more major or life-threatening bleeding, cardiogenic shock, acute kidney injury (stage II or III), and new-onset or worsening atrial fibrillation at 30 days than did TAVR-treated patients. CONCLUSIONS In the NOTION trial, no significant difference between TAVR and SAVR was found for the composite rate of death from any cause, stroke, or MI after 1 year. (Nordic Aortic Valve Intervention Trial [NOTION]; NCT01057173).

Metabolic and Vascular Effects of Tumor Necrosis Factor-α Blockade with Etanercept in Obese Patients with Type 2 Diabetes

Objective: The pro-inflammatory cytokine tumor necrosis factor-α (TNF-α) impairs insulin action in insulin-sensitive tissues, such as fat, muscle and endothelium, and causes endothelial dysfunction. We hypothesized that TNF-α blockade with etanercept could reverse vascular and metabolic insulin resistance. Method and Results: Twenty obese patients with type 2 diabetes were randomized to etanercept treatment (25 mg subcutaneously twice weekly for 4 weeks) or used as controls in an open parallel study. Forearm blood flow and glucose uptake were measured during intra-arterial infusions of serotonin, sodium nitroprusside and insulin co-infused with serotonin. β-Cell function was assessed with oral and intra-venous glucose tolerance tests and whole-body insulin sensitivity by hyperinsulinemic euglycemic clamps. Plasma levels of C-reactive protein and interleukin-6 decreased significantly with etanercept (C-reactive protein from 9.9 ± 3.1 to 4.8 ± 1.4 mg l–1, p = 0.04; interleukin-6 from 3.1 ± 0.4 to 1.9 ± 0.2 ng l–1, p = 0.03). Vasodilatory responses to serotonin and sodium nitroprusside infusions remained unchanged. Insulin effect on vasodilatation and on whole-body and forearm glucose uptake remained unchanged as well. β-Cell function tended to improve. Conclusion: Although short-term etanercept treatment had a significant beneficial effect on systemic inflammatory markers, no improvement of vascular or metabolic insulin sensitivity was observed.

Tumor Necrosis Factor-α Inhibits Insulin’s Stimulating Effect on Glucose Uptake and Endothelium-Dependent Vasodilation in Humans

Background—Inflammatory mechanisms could be involved in the pathogenesis of both insulin resistance and atherosclerosis. Therefore, we aimed at examining whether the proinflammatory cytokine tumor necrosis factor (TNF)-&agr; inhibits insulin-stimulated glucose uptake and insulin-stimulated endothelial function in humans. Methods and Results—Healthy, lean male volunteers were studied. On each study day, 3 acetylcholine (ACh) or sodium nitroprusside (SNP) dose-response studies were performed by infusion into the brachial artery. Before and during the last 2 dose-response studies, insulin and/or TNF-&agr; were coinfused. During infusion of insulin alone for 20 minutes, forearm glucose uptake increased by 220±44%. This increase was completely inhibited during coinfusion of TNF-&agr; (started 10 min before insulin) with a more pronounced inhibition of glucose extraction than of blood flow. Furthermore, TNF-&agr; inhibited the ACh forearm blood flow response (P <0.001), and this inhibition was larger during insulin infusion (P =0.01) but not further increased by NG-monomethyl-l-arginine acetate (P =0.2). Insulin potentiated the SNP response less than the ACh response and the effect of TNF-&agr; was smaller (P <0.001); TNF-&agr; had no effect on the SNP response without insulin infusion. Thus, TNF-&agr; inhibition of the combined response to insulin and ACh was likely mediated through inhibition of NO production. Conclusion—These results support the concept that TNF-&agr; could play a role in the development of insulin resistance in humans, both in muscle and in vascular tissue.

Transcatheter treatment of heart failure with preserved or mildly reduced ejection fraction using a novel interatrial implant to lower left atrial pressure

Heart failure with preserved or mildly reduced ejection fraction (HFpEF) is common and, to date, therapeutic options are limited. Increased left atrial pressure is a key contributor to the symptoms associated with HFpEF, particularly during physical activity. We report the 30‐day outcome of patients treated with a novel device intended to lower left atrial pressure by creating an 8 mm permanent shunt in the atrial septum.

Two-Year Outcomes in Patients With Severe Aortic Valve Stenosis Randomized to Transcatheter Versus Surgical Aortic Valve Replacement The All-Comers Nordic Aortic Valve Intervention Randomized Clinical Trial

Background—The Nordic Aortic Valve Intervention (NOTION) trial was the first to randomize all-comers with severe native aortic valve stenosis to either transcatheter aortic valve replacement (TAVR) with the CoreValve self-expanding bioprosthesis or surgical aortic valve replacement (SAVR), including a lower-risk patient population than previous trials. This article reports 2-year clinical and echocardiographic outcomes from the NOTION trial. Methods and Results—Two-hundred eighty patients from 3 centers in Denmark and Sweden were randomized to either TAVR (n=145) or SAVR (n=135) with follow-up planned for 5 years. There was no difference in all-cause mortality at 2 years between TAVR and SAVR (8.0% versus 9.8%, respectively; P=0.54) or cardiovascular mortality (6.5% versus 9.1%; P=0.40). The composite outcome of all-cause mortality, stroke, or myocardial infarction was also similar (15.8% versus 18.8%, P=0.43). Forward-flow hemodynamics were improved following both procedures, with effective orifice area significantly more improved after TAVR than SAVR (effective orifice area, 1.7 versus 1.4 cm2 at 3 months). Mean valve gradients were similar after TAVR and SAVR. When patients were categorized according to Society of Thoracic Surgeons Predicted Risk of Mortality (STS-PROM) (<4% versus ≥4%), there was no statistically significant difference for TAVR and SAVR groups in the composite outcome for low-risk (14.7%, 95% confidence interval, 8.3–21.2 versus 16.8%; 95% confidence interval, 9.7–23.8; P=0.58) or intermediate-risk patients (21.1% versus 27.1%; P=0.59). Conclusions—Two-year results from the NOTION trial demonstrate the continuing safety and effectiveness of TAVR in lower-risk patients. Longer-term data are needed to verify the durability of this procedure in this patient population. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT01057173.

Transcatheter treatment of heart failure with preserved or mildly reduced ejection fraction using a novel interatrial implant to lower left atrial pressure: IASD treatment of elevated filling pressures in HFpEF

Heart failure with preserved or mildly reduced ejection fraction (HFpEF) is common and, to date, therapeutic options are limited. Increased left atrial pressure is a key contributor to the symptoms associated with HFpEF, particularly during physical activity. We report the 30‐day outcome of patients treated with a novel device intended to lower left atrial pressure by creating an 8 mm permanent shunt in the atrial septum.

Transcatheter mitral valve implantation via transapical approach: an early experience

OBJECTIVES As many as 50% of patients with severe symptomatic mitral valve regurgitation are denied surgical valve replacement or repair due to high operative risk. We describe an early series of cases of transcatheter implantation with a CardiAQ™ mitral valve via a transapical approach. METHODS Three consecutive patients with an Society of Thoracic Surgeons (STS) mortality score of >22% were selected for transcatheter mitral valve implantation (TMVI) on compassionate grounds. All patients were elderly, had severe mitral regurgitation (MR), were in Class IV heart failure and deemed unsuitable for the MitraClip. Two of the patients had functional MR in the setting of ischaemic cardiomyopathy with left ventricular ejection fraction (LVEF) <40%, deemed while the remaining patient had chordal rupture with extensive anterior leaflet flail (preserved LVEF). Comorbidities included previous coronary artery bypass surgery (n = 2), severe pulmonary hypertension (n = 1) and moderate to severe chronic renal failure (n = 3). A CardiAQ mitral valve was implanted using fluoroscopy and transoesophageal (TEE) guidance via a standard transapical approach. RESULTS Accurate prosthesis positioning and deployment with immediate elimination of the MR was achieved in all 3 cases. Two patients made full clinical recovery and were discharged home. Post-procedural TEE performed on Days 1, 30 and 60 days showed good valve function, stable valve position and minimal LVOT gradient. One patient expired on the postoperative day 9 due to pneumonia. CONCLUSIONS TMVI using the CardiAQ™ device via a transapical approach is feasible and effective.

Percutaneous left atrial appendage occlusion for stroke prevention in atrial fibrillation: an update

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia encountered in clinical practice. One of its most devastating complications is the development of thromboembolism leading to fatal or disabling stroke. Oral anticoagulation (OAC, warfarin) is the standard treatment for stroke prevention in patients with AF with an increased stroke risk. However, there are several obstacles to long-term OAC therapy, including the risk of serious bleeding, several drug–drug interactions and the need for frequent blood testing. Although newer oral anticoagulants have been developed, these drugs also face issues of major bleeding and non-compliance. Therefore, alternative treatment options for stroke prevention in patients with AF with a high stroke risk are needed. Percutaneous left atrial appendage (LAA) occlusion is an evolving therapy, which should be taken into consideration in those patients with non-valvular AF with a high stroke risk and contraindications for OAC. This article aims to discuss the rationale for LAA closure, the available LAA occlusion devices and their clinical evidence until now. Moreover, we discuss the importance of proper patient selection, the role of various imaging techniques and the need for a more tailored postprocedural antithrombotic therapy.

Prosthetic Valve Endocarditis After Transcatheter Aortic Valve Implantation

Background—Transcatheter aortic valve implantation (TAVI) is an advancing mode of treatment for inoperable or high-risk patients with aortic stenosis. Prosthetic valve endocarditis (PVE) after TAVI is a serious complication, but only limited data exist on its incidence, outcome, and procedural risk factors. Methods and Results—Observational single-center study of 509 consecutive patients treated with a transcatheter implanted self-expandable aortic valve prosthesis (Medtronic CoreValve). We identified 18 patients diagnosed with TAVI-PVE during a median follow-up period of 1.4 years (interquartile range, 0.5–2.5 years; longest follow-up was 6.3 years). TAVI-PVE was most frequent in the first year after implantation (first-year incidence, 3.1% [confidence interval, 1.4%–4.8%]); the overall annualized rate was 2.1% per patient-year (confidence interval, 1.2%–3.3%). Seventeen patients (94%) were treated conservatively and 1 with surgery. Four patients (22%) died from endocarditis or complications to treatment, 2 of those (11%) during initial hospitalization for PVE. An increased risk of TAVI-PVE was seen in patients with low implanted valve position (hazard ratio, 2.8 [1.1–7.2]), moderate or worse postprocedural paravalvular regurgitation (hazard ratio, 4.0 [1.5–11]), implantation of >1 prosthesis (hazard ratio, 5.2 [1.5–18]), and any vascular complication (hazard ratio, 3.8 [1.5–9.8]). Conclusions—TAVI-PVE occurred at a slightly higher rate than reported for surgically implanted valves. Conservative treatment was associated with an acceptable outcome. Suboptimal valve deployment and vascular complications were associated with an increased risk of TAVI-PVE.

Infective endocarditis following percutaneous pulmonary valve replacement: Diagnostic challenges and application of intra-cardiac echocardiography

BACKGROUND Infective endocarditis (IE) following percutaneous pulmonary valve replacement (PPVR) with the Melody valve is rarely reported. Furthermore, there are challenges in this diagnosis; especially echocardiographic evidence of vegetation within the prosthesis may be difficult. METHOD AND RESULT This study is a retrospective review of all patients with Melody valve implantation in a tertiary centre. Between November 2006 and November 2012, 43 procedures were performed in 42 patients (mean age 25 years, 6-67 years). At a median follow-up of 27 months (2-66 months), six patients were suspected for IE. However, repeated transthoracic echocardiography (TTE) and transesophageal echocardiography (TEE) showed no evidence of IE and the patients were diagnosed as possible cases according to the modified Dukes criteria. Two patients did not respond to antibiotic treatment and underwent intra-cardiac echocardiography (ICE), which clearly demonstrated vegetations. These two cases required surgical explantation, while the other four patients were treated medically without complications. CONCLUSION IE after Melody valve implantation is uncommon, but difficult to verify since TTE and TEE often cannot demonstrate vegetations inside the stent. ICE should be considered in suspected cases of IE following PPVR with negative TTE and TEE examinations in order to early tailor the best treatment for the individual patient suspected for IE.