Influence of Culprit Lesion Intervention on Outcomes in Infarct-Related Cardiogenic Shock With Cardiac Arrest.

BACKGROUND: Cardiac arrest (CA) is common in patients with infarct-related cardiogenic shock (CS). OBJECTIVES: The goal of this study was to identify the characteristics and outcomes of culprit lesion percutaneous coronary intervention (PCI) of patients with infarct-related CS stratified according to CA in the CULPRIT-SHOCK (Culprit Lesion Only PCI Versus Multivessel PCI in Cardiogenic Shock) randomized trial and registry. METHODS: Patients with CS with and without CA from the CULPRIT-SHOCK study were analyzed. All-cause death or severe renal failure leading to renal replacement therapy within 30 days and 1-year death were assessed. RESULTS: Among 1,015 patients, 550 (54.2%) had CA. Patients with CA were younger, more frequently male, had lower rates of peripheral artery disease, a glomerular filtration rate <30 mL/min, and left main disease, and they presented more often with clinical signs of impaired organ perfusion. The composite of all-cause death or severe renal failure within 30 days occurred in 51.2% of patients with CA vs 48.5% in non-CA patients (P = 0.39) and 1-year death in 53.8% vs 50.4% (P = 0.29), respectively. In a multivariate analysis, CA was an independent predictor of 1-year mortality (HR: 1.27; 95% CI: 1.01-1.59). In the randomized trial, culprit lesion-only PCI was superior to immediate multivessel PCI in patients both with and without CA (P for interaction = 0.6). CONCLUSIONS: More than 50% of patients with infarct-related CS had CA. These patients with CA were younger and had fewer comorbidities, but CA was an independent predictor of 1-year mortality. Culprit lesion-only PCI is the preferred strategy, both in patients with and without CA. (Culprit Lesion Only PCI Versus Multivessel PCI in Cardiogenic Shock [CULPRIT-SHOCK]; NCT01927549).

Tumor necrosis factor alpha-an underestimated risk predictor in patients undergoing transcatheter aortic valve replacement (TAVR)?

BACKGROUND: Systemic inflammation has been identified as a major cardiovascular risk factor in patients undergoing transcatheter aortic valve replacement (TAVR), yet currently, it is not adequately portrayed in scores for pre-interventional risk assessment. The aim of this study was to investigate the predictive ability of TNF-α in TAVR. METHODS: A total of 431 patients undergoing transfemoral TAVR were enrolled in this study. Blood samples were drawn prior to intervention, 24 h post-intervention, 4, 5, and 7 days post-intervention, and 1, 3, and 6 months post-TAVR. RESULTS: In a univariate Cox proportional hazard analysis, plasma concentrations of TNF-α after 24 h and after 5 days were associated with mortality after 12 months (after 24 h: HR 1.002 (1.000-1.004), p = 0.028; after 5d: HR 1.003 (1.001-1.005), p = 0.013). This association remained significant even after correction for confounders in a multivariate Cox regression analysis. Additionally, cut-offs were calculated. Patients above the cut-off for TNF-α after 5d had a significantly worse 12-month mortality than patients below the cut-off (18.8% vs. 2.8%, p = 0.046). CONCLUSION: Plasma levels of TNF-α after 24 h and 5 days were independently associated with 12-month mortality in patients undergoing TAVR. Thus, TNF-α could represent a novel biomarker for enhanced risk stratification in these patients.

Investigating Aortic Valve Calcification via Isolation and Culture of T Lymphocytes using Feeder Cells from Irradiated Buffy Coat.

Calcific aortic valve disease (CAVD), an active disease process ranging from mild thickening of the valve to severe calcification, is associated with high mortality, despite new therapeutic options such as transcatheter aortic valve replacement (TAVR). The complete pathways that start with valve calcification and lead to severe aortic stenosis remain only partly understood. By providing a close representation of the aortic valve cells in vivo, the assaying of T lymphocytes from stenotic valve tissue could be an efficient way to clarify their role in the development of calcification. After surgical excision, the fresh aortic valve sample is dissected in small pieces and the T lymphocytes are cultured, cloned then analyzed using fluorescence activated cell sorting (FACS). The staining procedure is simple and the stained tubes can also be fixed using 0.5% of paraformaldehyde and analyzed up to 15 days later. The results generated from the staining panel can be used to track changes in T cell concentrations over time in relation to intervention and could easily be further developed to assess activation states of specific T cell subtypes of interest. In this study, we show the isolation of T cells, performed on fresh calcified aortic valve samples and the steps of analyzing T cell clones using flow cytometry to further understand the role of adaptive immunity in CAVD pathophysiology.

Transcatheter therapies for severe tricuspid regurgitation. Quo vadis?

Moderate-to-severe tricuspid regurgitation (TR) is common and is associated with a poor prognosis. To date, most patients are undertreated; therefore, transcatheter options could be clinically impactful in those who are denied surgery. Several transcatheter solutions have been developed that address the problem via leaflet enhancement, annuloplasty, or heterotopic implantation of self-expandable or balloon-expandable valves in the caval veins. A comprehensive patient evaluation, based on multimodality imaging techniques for a better understanding of the valvular pathology and TR mechanism, remains paramount for an appropriate device selection. To date, several trials have shown the feasibility and safety of a multitude of devices in this setting, but data from randomized clinical trials regarding clinical benefit based on hard endpoints are still lacking. Although the optimal patient profile and timing of intervention remain under investigation, data from available studies indicate that an earlier treatment referral, before onset of irreversible right ventricular remodeling, could be beneficial. This review discusses the present landscape and future implications of transcatheter therapies for severe TR.

Transcatheter valve-in-valve implantation (VinV-TAVR) for failed surgical aortic bioprosthetic valves.

OBJECTIVE: We sought to investigate the procedural and hemodynamic outcome after valve-in-valve transcatheter aortic valve replacement (VinV-TAVR) for different surgical (SBV) and transcatheter (TAVR) bioprosthetic valves. METHODS AND RESULTS: 223 patients (76 ± 11years, STS-Score 8.3 ± 10.1) suffering from SBV failure treated with VinV-TAVR were enrolled at 6 centers across Germany. At time of the intervention, the majority of patients were in NYHA-class ≥ III (88%, n = 180). Failure mode of the SBVs was either stenosis, regurgitation (AR) or a combination of both in 85 (38%), 76 (34%) and 62 (28%) patients, respectively. 138 (62%) patients were treated with first generation TAVR valves (Edwards Sapien XT or CoreValve). Second generation valves were implanted in 85 (38%) patients (Sapien 3, Medtronic CoreValve Evolut, SJM-Portico, JenaValve). VinV-TAVR was associated with high procedural success rate, conversion to surgery was necessary in 3 (2%) patients. After VinV-TAVR procedure, 4 (2%) patients suffered from ≥ moderate AR. In 6 (3%) patients a second valve was implanted due to mispositioning of the first valve and subsequent severe paravalvular AR. Coronary obstruction was observed in 4 (2%) patients. Major bleeding and cerebrovascular complications (according to VARC) were reported in 3 (1%) and 4 (2%) patients at 30 days. Post-interventionally, 44/178 (25%) patients evidenced a mean pressure gradient (mPG) ≥ 20 mmHg. Residual stenosis was not associated with increased mortality (HR 0.39; 95% CI 0.13-1.22; p = 0.11). CONCLUSION: In VinV-TAVR for SBV-failure is a safe procedure resulting in hemodynamic improvement in the majority of patients. Residual stenosis is a common finding which can be observed in 1/4 of patients undergoing VinV-TAVR. However, this condition is not associated with increased 1-year-mortality.

Tricuspid Regurgitation - Medical Management and Evolving Interventional Concepts.

Severe tricuspid regurgitation (TR) is a complex condition of the right ventricle (RV) and tricuspid valve apparatus and is frequently associated with symptomatic heart failure and a significant morbidity and mortality. In these patients, left heart pathologies lead to chronic pressure overload of the RV, eventually causing progressive RV dilatation and functional TR. Therefore, TR cannot be considered as isolated heart valve disease pathology but has to be understood and treated as one component of a complex structural RV pathology and is frequently also a marker of an advanced stage of cardiac disease. In these patients, medical therapy restricted to diuretics and heart failure medication is frequently ineffective. Also, severe TR in the setting of advanced heart failure constitutes a high risk for cardiac surgery. Neither one of these treatment options has demonstrated a beneficial effect on long-term prognosis. The recent innovations in transcatheter technology led to efforts to develop interventional approaches to severe TR. Multiple innovative treatment concepts are currently under preclinical and clinical investigation to replace or repair TV function. However, up to date none of these approaches is established and there is still a lack of clinical data to support the efficacy of transcatheter TR treatment.

Interventional Treatment of Severe Tricuspid Regurgitation: Early Clinical Experience in a Multicenter, Observational, First-in-Man Study.

BACKGROUND: Transcatheter caval valve implantation is under evaluation as a treatment option for inoperable patients with severe tricuspid regurgitation (TR). The procedure involves the catheter-based implantation of bioprosthetic valves in the inferior vena cava and superior vena cava to treat symptoms associated with TR. This study is the first to evaluate the feasibility, safety, and efficacy of this interventional concept. METHODS AND RESULTS: Twenty-five patients (mean age, 73.9±7.6 years; women, 52.0%) with severe symptomatic TR despite optimal medical treatment deemed unsuitable for surgery were treated with caval valve implantation under a compassionate clinical use program. Technical feasibility defined as procedural success, hemodynamic effect defined as venous pressure reduction, and safety defined as periprocedural adverse events were evaluated, with clinical follow-up at discharge and up to 12 months. The functional impact was evaluated by assessment of New York Heart Association class at the time of hospital discharge. The total number of valves implanted in the caval position was 31. Patients were treated with single (inferior vena cava-only; n=19; 76.0%) or bicaval valve implantation (inferior vena cava+superior vena cava; n=6; 24.0%). Either balloon-expandable valves (Sapien XT/3: n=18; 72.0%) or self-expandable valves (TricValve: n=6; 24.0%; Directflow: n=1; 4.0%) were used. Procedural success was achieved in 96% (n=24). Early and late valve migration requiring surgical intervention occurred in 1 patient each. Thirty-day and in-hospital mortality were 8% (2 of 25) and 16% (4 of 25). Causes of in-hospital mortality included respiratory (n=1) or multiple organ failure (n=3) and were not linked to the procedure. Mean overall survival in the study cohort was 316±453 days (14-1540 days). CONCLUSIONS: Caval valve implantation for the treatment of severe TR and advanced right ventricular failure is associated with a high procedural success rate and seems safe and feasible in an excessive-risk cohort. The study demonstrates hemodynamic efficacy with consistent elimination of TR-associated venous backflow and initial clinical improvement. These results encourage further trials to determine which patients benefit most from this interventional approach.

Restrictive cardiomyopathy : Delayed occurrence after radiotherapy of breast cancer.

A 74-year-old female patient was referred to our department in 2015 with dyspnea, cough and dysphagia. She had been diagnosed with adenocarcinoma of the right breast in 1986 and underwent mastectomy. When she presented with a local recurrence in 1988, she was receiving high-voltage radiation therapy. Transthoracic echocardiography and magnetic resonance imaging revealed tricuspid regurgitation grade III and unclear right heart failure with a massively dilated right atrium. Coronary heart disease could be ruled out. In summary, the patient's findings represented right ventricular myocardial restriction which we attributed to irradiation of the right anterior chest 17 years previously.

Protein disulfide isomerase A3-specific Th1 effector cells infiltrate colon cancer tissue of patients with circulating anti-protein disulfide isomerase A3 autoantibodies.

To investigate novel colorectal cancer (CRC)-associated antigens that could be targets of humoral or cellular responses, we analyzed the reactivity of serum from a long-surviving CRC patient (for more than 100 months of follow-up) in clinical remission, by serologic proteome analysis. Two-dimensional Western blotting (2D-WB) and mass spectrometry analysis revealed a strong reactivity of this serum against protein disulfide isomerase A3 (PDIA3). Anti-PDIA3 antibodies are not a diagnostic marker of CRC, 2D-WB and Luminex analysis revealed that they were equally present in about 10% of sera from healthy subjects and CRC patients. Kaplan-Meier analysis of survival in CRC patient cohort, after 48 months of follow-up, showed a trend of higher survival in patients with increased levels of autoantibodies to PDIA3. Therefore, the interplay between the presence of these antibodies and T-cell response was investigated. Peripheral blood T cells from CRC patients with high immunoglobulin G (IgG) reactivity to PDIA3 also secreted interferon gamma (IFN-γ) when stimulated in vitro with recombinant PDIA3, whereas those from CRC with low IgG reactivity to PDIA3 did not. PDIA3-pulsed dendritic cells efficiently induced proliferation and IFN-γ production of autologous CD4(+) and CD8(+) T cells. Finally, ex vivo analysis of tumor-infiltrating T lymphocytes from CRC patients with autoantibodies to PDIA3 revealed that PDIA3-specific Th1 effector cells accumulated in tumor tissue. These data indicate that the presence of autoantibodies to PDIA3 favors the development of an efficient and specific T-cell response against PDIA3 in CRC patients. These results may be relevant for the design of novel immunotherapeutic strategies in CRC patients.