Tricuspid regurgitation (TR) is a frequent disease with a progressive increase in mortality as disease severity increases. Transcatheter therapies for treatment of TR may offer a safe and effective ...alternative to surgery in this high-risk population.
The purpose of this report was to study the 1-year outcomes with the TriClip transcatheter tricuspid valve repair system, including repair durability, clinical benefit and safety.
The TRILUMINATE trial (n = 85) is an international, prospective, single arm, multicenter study investigating safety and performance of the TriClip Tricuspid Valve Repair System in patients with moderate or greater TR. Echocardiographic assessment was performed by a core laboratory.
At 1 year, TR was reduced to moderate or less in 71% of subjects compared with 8% at baseline (p < 0.0001). Patients experienced significant clinical improvements in New York Heart Association (NYHA) functional class I/II (31% to 83%, p < 0.0001), 6-minute walk test (272.3 ± 15.6 to 303.2 ± 15.6 meters, p = 0.0023) and Kansas City Cardiomyopathy Questionnaire (KCCQ) score (improvement of 20 ± 2.61 points, p < 0.0001). Significant reverse right ventricular remodeling was observed in terms of size and function. The overall major adverse event rate and all-cause mortality were both 7.1% at 1 year.
Transcatheter tricuspid valve repair using the TriClip device was found to be safe and effective in patients with moderate or greater TR. The repair itself was durable at reducing TR at 1 year and was associated with a sustained and marked clinical benefit with low mortality after 1 year in a fragile population that was at high surgical risk. (TRILUMINATE Study With Abbott Transcatheter Clip Repair System in Patients With Moderate or Greater TR; NCT03227757)
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Abstract
Aims
Patients with pulmonary hypertension (PHT) are often excluded from surgical therapies for tricuspid regurgitation (TR). Transcatheter tricuspid valve repair (TTVR) with the MitraClip™ ...technique is a novel treatment option for these patients. We aimed to assess the role of PHT in severe TR and its implications for TTVR.
Methods and results
A total of 243 patients underwent TTVR at two centres. One hundred twenty-one patients were grouped as iPHT+ invasive systolic pulmonary artery pressures (PAPs) ≥50 mmHg. Patients were similarly stratified according to echocardiographic PAPs (ePHT). The occurrence of the combined clinical endpoint (death, heart failure hospitalization, and reintervention) was investigated during a follow-up of 330 (interquartile range 175–402) days. iPHT+ patients were at higher preoperative risk (P < 0.01), had more severe symptoms (P = 0.01), higher N-terminal pro-B-type natriuretic peptide levels (P < 0.01), more impaired right ventricular (RV) function (P < 0.01), and afterload corrected RV function (P < 0.01). Procedural TTVR success was similar in iPHT+ and iPHT− patients (84 vs. 84%, P = 0.99). The echocardiographic diagnostic accuracy to detect iPHT was only 55%. During follow-up, 35% of patients reached the combined clinical endpoint. The discordant diagnosis of iPHT+/ePHT− carried the highest risk for the combined clinical endpoint HR 3.76 (CI 2.25–6.37), P < 0.01, while iPHT+/ePHT+ patients had a similar survival-free time from the combined endpoint compared to iPHT− patients (P = 0.48). In patients with isolated tricuspid procedure (n = 131) a discordant iPHT+/ePHT− diagnosis and an impaired afterload corrected RV function (P < 0.01 for both) were independent predictors for the occurrence of the combined endpoint.
Conclusion
The discordant echocardiographic and invasive diagnosis of PHT in severe TR predicts outcomes after TTVR.
This study was designed to assess hemodynamic changes in response to transcatheter tricuspid valve edge-to-edge repair (TTVR) and to identify hemodynamic predictors associated with mortality.
Severe ...tricuspid regurgitation (TR) is associated with high mortality. TTVR effectively alleviates heart failure symptoms, but comprehensive hemodynamic characterization of patients undergoing TTVR is currently lacking.
This international, multicenter study included 236 patients undergoing TTVR. Data from clinical assessment, echocardiography, intraprocedural right heart catheterization, and noninvasive cardiac output measurement were analyzed. Hemodynamic predictors for mortality were identified using linear Cox regression analysis and were used for stratification of patients with subsequent analysis of survival time.
Patients (median age 78 years, 53% women) were symptomatic (89% in New York Heart Association functional class III or IV) because of severe TR (grade ≥3+ in 100%). TTVR significantly reduced TR at discharge (grade ≥3+ in 16%; p < 0.001), with a corresponding 19% reduction of the right atrial v wave (21 mm Hg vs. 16 mm Hg; p < 0.001) and an improvement in cardiac output (from 3.5 to 4.0 l/min; p < 0.01). Invasive mean pulmonary artery pressure, transpulmonary gradient, pulmonary vascular resistance, and right ventricular stroke work were significant predictors of 1-year mortality (p < 0.05 for all). Hemodynamic stratification by mean pulmonary artery pressure and transpulmonary gradient best predicted 1-year survival (p < 0.001). Although patients with pre-capillary dominant pulmonary hypertension showed an unfavorable prognosis (1-year survival 38%), patients without or with post-capillary pulmonary hypertension had favorable outcome (1-year survival 92% or 78%, respectively).
Invasive assessment of cardiopulmonary hemodynamic status predicts survival after TTVR. Invasive hemodynamic characterization may help identify patients profiting most from TTVR.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The increasing interest in left atrial appendage occlusion (LAAO) for ischaemic stroke prevention in atrial fibrillation (AF) fuels the need for more clinical data on the safety and effectiveness of ...this therapy. Besides an assessment of the effectiveness of the therapy in specific patients groups, comparisons with pharmacological stroke prophylaxis, surgical approaches, and other device-based therapies are warranted. This paper documents the consensus reached among clinical experts in relevant disciplines from Europe and North America, European cardiology professional societies, and representatives from the medical device industry regarding definitions for parameters and endpoints to be assessed in clinical studies. Adherence to these definitions is proposed in order to achieve a consistent approach across clinical studies on LAAO among the involved stakeholders and various clinical disciplines and thereby facilitate continued evaluation of therapeutic strategies available.
The aim of this study was to investigate the procedural feasibility and short-term durability of the transcatheter tricuspid valve edge-to-edge repair technique in highly symptomatic patients with ...severe tricuspid regurgitation (TR).
Eighteen consecutive patients suffering from severe right-sided heart failure (NYHA Class III-IV), primarily due to moderate to severe tricuspid regurgitation, were included in the study. Applying a modified steering technique for the clip delivery system, six patients were treated for isolated severe TR, while 12 patients were treated for moderate to severe TR and concomitant severe mitral regurgitation. The primary objectives were procedural success, defined as reduction of at least one TR grade, and 30-day echocardiographic and clinical outcomes. A total of 41 clips (2.3±0.7 per patient) were placed into the tricuspid valve of high surgical risk patients (EuroSCORE II: 10±8%). Procedural success was achieved in all patients; no MACCE occurred in hospital. The presence of a TR grade ≥3 was reduced from 94% (17 patients) before the procedure to 33% (six patients) at 30-day follow-up (p<0.001). Sixteen patients (89%) reported an improvement in NYHA functional class at 30 days.
Applying a modified steering technique, the edge-to-edge repair technique can be successfully used for the treatment of TR. At 30-day follow-up, the short-term durability of TR reduction appeared promising and the majority of patients improved clinically. Further studies with larger patient populations and longer follow-up have to define the role of this novel treatment option for patients with right-sided heart failure and severe TR.
Background Right‐sided heart failure (HF) due to severe tricuspid regurgitation (TR) is associated with reduced quality of life (QoL). Here, we analyzed the impact of TR on specific QoL dimensions ...and the effect of transcatheter tricuspid valve intervention (TTVI) on individual QoL items. Methods and Results In this study, we included 174 patients with HF (49% women; median age, 79 years; 97% New York Heart Association ≥3) with baseline QoL assessment undergoing TTVI by transcatheter edge‐to‐edge‐repair at our center between April 2016 and March 2022. QoL was assessed by the standardized Minnesota Living With HF Questionnaire. QoL change after TTVI and correlation to functional end points were analyzed. In addition, all QoL domains and the 21 individual items of the Minnesota Living With HF Questionnaire were analyzed. TTVI significantly reduced TR (TR ≥3: baseline 95%, 1‐year‐follow‐up 7%; P <0.001). Total Minnesota Living with HF Questionnaire score improved from 37 (interquartile range, 26–50) points to 31 (interquartile range, 17–42) points (median follow‐up‐interval, 355 days; P <0.001). QoL improvement was associated with positive New York Heart Association class, 6‐minute walking distance, and actigraphy changes (all P <0.05). The detailed analysis revealed that all items of the physical‐related QoL dimension were impaired at baseline and strongly improved after TTVI. In contrast, the emotional and “social” Minnesota Living With HF Questionnaire dimensions were largely unaffected at baseline, yet specific items improved with TTVI. Conclusions In this single‐center study, we delineate the QoL‐associated disease burden of TR and identify specific QoL items that improved after TTVI. Our findings support TTVI in patients with reduced QoL and may add to the development of specific tools assessing the functional status of an increasing patient population undergoing TTVI.
OBJECTIVE—Anti-inflammatory effects of statins contribute to their clinical benefit. Molecular mechanisms underlying these effects have not been well explored. Because statins attenuate ...lipopolysaccharide (LPS) responsiveness, we hypothesized that part of the pleiotropic effects are mediated through innate immunity.
METHODS AND RESULTS—Toll-like receptor (TLR) 4 expression and downstream signaling in CD14 monocytes after incubation with simvastatin and atorvastatin were quantified via flow-cytometry, quantitative RT-PCR, kinase assay, and enzyme-linked immunosorbent assay. Incubation with intermediates/ inhibitors of the mevalonate pathway was used to identify the mode of statin action. Statin incubation resulted in a dose-dependent reduction of TLR4 expression (53±7.6% reduction compared with untreated monocytes; P<0.005), transcript levels (68±6.3%; P<0.002), decreased IRAK phosphorylation (37±8.3%; P<0.05), and LPS-induced IL-6, IL-12, tumor necrosis factor (TNF)-α, and B7-1 expression (P<0.05). Four weeks of treatment with atorvastatin significantly reduced TLR4 expression on circulating CD14 monocytes by 36.2±4.2% (P<0.05). Effects of statins were reversed by mevalonate (P=0.57). Incubation with specific inhibitors of geranylgeranyltransferase (54±4.3%), farnesyltransferase (57±5.1%), or with clostridium-difficile toxin B (58±6.1%, P<0.01) imitated the statin effects. Whereas wortmannin and LY294002 inhibited the statin effect (P=0.27), incubation with a specific RhoA kinase inhibitor had no effect (P=0.57).
CONCLUSIONS—Statins influence TLR4 expression and signaling via inhibition of protein geranylgeranylation and farnesylation. These observations imply interactions with innate immunity as one pleiotropic mechanism.
We present 2 cases of significant mitral regurgitation secondary to pericardial patch avulsion from the anterior mitral valve leaflet after aortic valve replacement with aortic annulus enlargement. ...Both cases were successfully managed by transcatheter repair with off-label implantation of occluder devices.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Identification of a Common Gene Expression Signature in Dilated Cardiomyopathy Across Independent Microarray Studies
Andreas S. Barth, Ruprecht Kuner, Andreas Buness, Markus Ruschhaupt, Sylvia Merk, ...Ludwig Zwermann, Stefan Kääb, Eckart Kreuzer, Gerhard Steinbeck, Ulrich Mansmann, Annemarie Poustka, Michael Nabauer, Holger Sültmann
Although microarrays have emerged as a powerful tool for delineating complex disease patterns, differences in platform technology, tissue heterogeneity, and small sample sizes hamper a comprehensive interpretation of microarray studies in heart failure. Therefore, we performed 2 cDNA and oligonucleotide microarray studies with septal and left ventricular tissue from nonfailing and DCM hearts (each n = 20). Immune response processes displayed the most pronounced regulation on both microarray platforms. Furthermore, a robust set of 27 genes was identified that classified DCM and NF samples in our own microarray studies as well as in 2 additional publicly available datasets (total of 108 samples) with >90% accuracy.
This study was designed to identify a common gene expression signature in dilated cardiomyopathy (DCM) across different microarray studies.
Dilated cardiomyopathy is a common cause of heart failure in Western countries. Although gene expression arrays have emerged as a powerful tool for delineating complex disease patterns, differences in platform technology, tissue heterogeneity, and small sample sizes obscure the underlying pathophysiologic events and hamper a comprehensive interpretation of different microarray studies in heart failure.
We accounted for tissue heterogeneity and technical aspects by performing 2 genome-wide expression studies based on cDNA and short-oligonucleotide microarray platforms which comprised independent septal and left ventricular tissue samples from nonfailing (NF) (n = 20) and DCM (n = 20) hearts.
Concordant results emerged for major gene ontology classes between cDNA and oligonucleotide microarrays. Notably, immune response processes displayed the most pronounced down-regulation on both microarray types, linking this functional gene class to the pathogenesis of end-stage DCM. Furthermore, a robust set of 27 genes was identified that classified DCM and NF samples with >90% accuracy in a total of 108 myocardial samples from our cDNA and oligonucleotide microarray studies as well as 2 publicly available datasets.
For the first time, independent microarray datasets pointed to significant involvement of immune response processes in end-stage DCM. Moreover, based on 4 independent microarray datasets, we present a robust gene expression signature of DCM, encouraging future prospective studies for the implementation of disease biomarkers in the management of patients with heart failure.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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