Clinical Research in Cardiology

A high, Doppler-derived, tricuspid regurgitation velocity (TRV) indicates pulmonary hypertension, which may contribute to right ventricular dysfunction and worsening tricuspid regurgitation leading to systemic venous congestion, reflected by an increase in inferior vena cava (IVC) diameter. We hypothesized that venous congestion rather than pulmonary hypertension would be more strongly associated with prognosis. 895 patients with chronic heart failure (CHF) (median (25th and 75th centile) age 75 (67–81) years, 69% men, LVEF 44 (34–55)% and NT-proBNP 1133 (423–2465) pg/ml) were enrolled. Compared to patients with normal IVC (< 21 mm) and TRV (≤ 2.8 m/s; n = 504, 56%), those with high TRV but normal IVC (n = 85, 9%) were older, more likely to be women and to have LVEF ≥ 50%, whilst those with dilated IVC but normal TRV (n = 142, 16%) had more signs of congestion and higher NT-proBNP. Patients (n = 164, 19%) with both dilated IVC and high TRV had the most signs of congestion and the highest NT-proBNP. During follow-up of 860 (435–1121) days, 239 patients died. Compared to those with both normal IVC and TRV (reference), patients with high TRV but normal IVC did not have a significantly increased mortality (HR: 1.41; CI: 0.87–2.29; P = 0.16). Risk was higher for patients with a dilated IVC but normal TRV (HR: 2.51; CI: 1.80–3.51; P < 0.001) or both a dilated IVC and elevated TRV (HR: 3.27; CI: 2.40–4.46; P < 0.001). Amongst ambulatory patients with CHF, a dilated IVC is more closely associated with an adverse prognosis than an elevated TRV.

After transcatheter aortic valve implantation, early leaflet thickening, presumably reflecting thrombus, has recently been described on computed tomography angiography (CTA) in ~10% of the patients. We sought to investigate the impact of the antithrombotic regimen on the course of leaflet thickening. The study comprised 51 patients with leaflet thickening. Based on the time period, patients without an established indication for anticoagulation were put on phenprocoumon plus clopidogrel for at least 3 months or on dual antiplatelet therapy with aspirin and clopidogrel. Follow-up CTAs were evaluated for leaflet restriction, assessed by four-point-grading score, and maximal thickness. The anticoagulation and the dual antiplatelet therapy group comprised 29 and 22 patients, respectively. After a median of 86 days, we obtained follow-up CTAs in 22 patients on anticoagulation and in 16 patients on dual antiplatelet therapy. Leaflet thickening progressed in 11 on dual antiplatelet therapy, but always regressed onanticoagulation. The course of leaflet restriction and maximal thickness was significantly different between the two groups (P < 0.001): in the dual antiplatelet therapy group, maximal thickness increased by a mean of 1.37 ± 1.67 mm (P = 0.005) and leaflet restriction score by a median 1[quartiles 0;2] (P = 0.013), whereas in the anticoagulation group, maximal thickness regressed by 2.57 ± 1.52 mm (P < 0.001) and leaflet restriction score decreased by 1[−4;0] (P = 0.001). After a median of 91 days after discontinuation of anticoagulation, CTA performed in ten patients revealed a significant recurrent increase in leaflet restriction score and maximal thickness (P = 0.023, P = 0.007). In the entire cohort, changes in leaflet restriction correlated significantly with changes in transvalvular pressure gradients (r = 0.511, P < 0.001). The course of leaflet restriction was fundamentally different depending on the presence or absence of anticoagulation, with consistent regression under phenprocoumon, but mostly progression under antiplatelet therapy alone. Changes in leaflet restriction were associated with changes in transvalvular pressure gradients.

Sympathetic activity plays an important role in the pathogenesis of ventricular tachyarrhythmia. Catheter-based renal sympathetic denervation (RDN) is a novel treatment option for patients with resistant hypertension, proved to reduce local and whole-body sympathetic activity. Two patients with chronic heart failure (CHF) (non-obstructive hypertrophic and dilated cardiomyopathy, NYHA III) suffering from therapy resistant electrical storm underwent therapeutic renal denervation. In both patients, RDN was conducted with agreement of the local ethics committee and after obtaining informed consent. The patient with hypertrophic cardiomyopathy had recurrent monomorphic ventricular tachycardia despite extensive antiarrhythmic therapy, following repeated endocardial and epicardial electrophysiological ablation attempts to destroy an arrhythmogenic intramural focus in the left ventricle. The second patient, with dilated nonischemic cardiomyopathy, suffered from recurrent episodes of polymorphic ventricular tachycardia and ventricular fibrillation. The patient declined catheter ablation of these tachycardias. In both patients, RDN was performed without procedure-related complications. Following RDN, ventricular tachyarrhythmias were significantly reduced in both patients. Blood pressure and clinical status remained stable during the procedure and follow-up in these patients with CHF. Our findings suggest that RDN is feasible even in cardiac unstable patients. Randomized controlled trials are urgently needed to study the effects of RD in patients with electrical storm and CHF.

While pulmonary hypertension (PH) in patients with severe aortic valve stenosis (AS) is associated with increased mortality after transcatheter aortic valve replacement (TAVR), there is limited data on gender differences in the effects on long-term survival. The aim of this retrospective, multicenter study was to investigate the prognostic impact of pre-interventional PH on survival of TAVR patients with respect to gender. 303 patients undergoing TAVR underwent echocardiography to detect PH prior to TAVR via measurement of systolic pulmonary artery pressure (sPAP). Different cut-off values were set for the presence of PH. The primary endpoint was all-cause mortality at 1, 3 and 5 years. Kaplan–Meier analysis by gender showed that only males exhibited significant increased mortality at elevated sPAP values during the entire follow-up period of 5 years (sPAP ≥ 40 mmHg: p ≤ 0.001 and sPAP ≥ 50 mmHg: p ≤ 0.001 in 1- to 5-year survival), whereas high sPAP values had no effect on survival in females. In Cox regression analysis based on the selected sPAP thresholds, male gender was an independent risk factor for long-term mortality after TAVR in all time courses. Male gender was an isolated risk factor for premature death after TAVR in patients with echocardiographic evidence of PH and severe AS. This could mean that, the indication for TAVR should be discussed more critically in men with severe AS and an elevated sPAP, while in females, PH should not be an exclusion criterion for TAVR. Graphical abstract of the study (Created with BioRender.com) Image material of CoreValve™ Evolut™ was kindly provided by © Medtronic Inc.

The aim of this health economic analysis was to compare the cost-effectiveness of ticagrelor versus clopidogrel within the German health care system. A two-part decision model was adapted to compare treatment with ticagrelor or clopidogrel in a low-dose acetylsalicylic acid (ASA) cohort (≤150 mg) for all ACS patients and subtypes NSTEMI/IA and STEMI. A decision-tree approach was chosen for the first year after initial hospitalization based on trial observations from a subgroup of the PLATO study. Subsequent years were estimated by a Markov model. Following a macro-costing approach, costs were based on official tariffs and published literature. Extensive sensitivity analyses were performed to test the robustness of the model. One-year treatment with ticagrelor is associated with an estimated 0.1796 life-years gained (LYG) and gained 0.1570 quality-adjusted life-years (QALY), respectively, over the lifetime horizon. Overall average cost with ticagrelor is estimated to be EUR 11,815 vs. EUR 11,387 with generic clopidogrel over a lifetime horizon. The incremental cost-effectiveness ratio (ICER) was EUR 2,385 per LYG (EUR 2,728 per QALY). Comparing ticagrelor with Plavix® or the lowest priced generic clopidogrel, ICER ranges from dominant to EUR 3,118 per LYG (EUR 3,567 per QALY). These findings are robust under various additional sensitivity analyses. Hence, 12 months of ACS treatment using ticagrelor/ASA instead of clopidogrel/ASA may offer a cost-effective therapeutic option, even when the generic price for clopidogrel is employed.

Percutaneous edge-to-edge repair with the MitraClip device has been shown to allow effective treatment of mitral regurgitation. It is mainly guided by transesophageal echocardiography while fluoroscopic guidance is of less importance. The impact of real-time three-dimensional transesophageal echocardiography (RT 3-D TEE) for guidance of this complex interventional procedure has not been evaluated. In 28 high-surgical risk patients with moderate or severe mitral regurgitation (mean age 67 ± 10 years; 15 male), 2-D and RT 3-D TEE were used for the guidance of percutaneous edge-to-edge mitral valve repair using the MitraClip device. We performed a structured analysis to compare information and guidance capacity provided by RT 3-D TEE compared to 2-D TEE. RT 3-D TEE was found to provide advantages in 9 of 11 steps of the percutaneous mitral repair procedure. The advantages related to optimized definition of the transseptal puncture site, improved guidance of the clip delivery system towards the mitral valve, precise positioning of the clip delivery system simultaneously in anterior–posterior and lateral–medial direction above the mitral valve considering mitral valve scallops A2 and P2 and valvular regurgitation jet position, adjustment of the opened clip-arms perpendicular to the commissural line, visualization of the clip position relative to the valvular orifice and of the remaining regurgitant jet after clip closure from atrial as well as ventricular views providing double orifice images and thereby allowing confirmation or rejection of clip position in medial–lateral direction. RT 3-D TEE was inferior to 2-D TEE for leaflet grasping and analysis of leaflet insertion. In complex interventional edge-to-edge repair with the MitraClip device requiring optimal spatial information RT 3-D TEE allows improved guidance of the procedure. RT 3-D TEE guidance compared with 2-D TEE guidance alone resulted in greater operator confidence to adequately perform the procedure.

Treatment with warfarin greatly reduces the risk of stroke related to atrial fibrillation, but will not be effective unless patients adhere to treatment. Lack of fixed dosing makes it difficult to objectively estimate adherence to treatment from prescription data. To evaluate two methods that assess adherence to warfarin from prescription data. Retrospective study of Swedish health care registers. Age- and sex-specific dose requirements were determined from approx. 1 million blood tests and dosing instructions. By applying these dosages to 163,785 warfarin-treated patients with atrial fibrillation, we calculated the quantity of warfarin that was needed to keep these patients on effective treatment during a mean follow-up of 3.9 years and compared that with the dispensed quantities. The ratio of available drug/time at risk constitutes a measure of adherence on group level. In addition, time intervals between refills were used to assess discontinuation. Both methods showed that 45 % of the patients did not have enough warfarin to last 80 % of the time at risk. Between 16 and 21 % of the patients discontinued within the first year, followed by 8–9 % annually during the following years. Patients with high bleeding risk and patients with low embolic risk showed lower endurance. Adherence to treatment with warfarin can be estimated on group level from prescription data and may be useful for comparison of adherence with warfarin and new oral anticoagulants. When applied to a large warfarin-treated cohort with atrial fibrillation, we found that adherence is low and that measures aiming for improvements are needed .