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).

The SALINE Technique for the Treatment of the No-Reflow Phenomenon during Percutaneous Coronary Intervention in STEMI.

BACKGROUND: Primary percutaneous coronary intervention (pPCI) performed for STEMI may be complicated by the "no-reflow" phenomenon. AIMS: A super-selective intracoronary injection of saline solution through a thrombus aspiration catheter (SALINE technique), was investigated for the treatment of no-reflow as compared with the standard care of therapy (SCT). METHODS: Among the 1471 patients with STEMI undergoing pPCI between May 2015 and June 2020, 168 patients developed no-reflow. Primary endpoints were the incidence of ST-segment resolution (STR) ≥ 70% at 90 min after PCI and the rate of flow restoration (TIMI flow grade 3 with an MBG > 1). The secondary endpoint was the incidence of major adverse cardiac and cerebrovascular events at 3 years follow-up. RESULTS: After propensity score matching analysis, patients treated with SALINE showed STR ≥ 70% in twelve out of the sixteen patients (75.0%), compared to only three patients out of the sixteen in the SCT control group (19.0%), (p < 0.004). SALINE was associated with a higher probability of final TIMI flow grade 3 with an MBG > 1, as shown in fourteen out of sixteen patients (87.5%), as compared to only seven out of sixteen patients in the SCT group (43.8%), (p < 0.03). MACCE at 3 years follow-up occurred in only one patient (6.3%) in the SALINE group, as compared to eight patients (50%) in the SCT group (p = 0.047). CONCLUSIONS: The SALINE technique showed to be a safe and effective strategy to reduce "no-reflow" in STEMI patients as assessed by significant STR, improvement of TIMI flow grade, and better 3-year outcomes.

The first taxonomic and functional characterization of human CAVD-associated microbiota.

Introduction: Calcific aortic valve disease (CAVD) is the most common heart valve disorder, defined by a remodeling multistep process: namely, valve fibrosis with its area narrowing, impaired blood flow, and final calcification phase. Nowadays, the only treatment is the surgical valve replacement. As for other cardiovascular diseases, growing evidence suggest an active role of the immune system in the calcification process that could be modulated by the microbiota. To address this point, we aimed to investigate and characterize, for the first time, the presence of a valve microbiota and associated immune response in human CAVD. Method: Calcified aortic valve (CAV) samples from twenty patients (11 from Germany and 9 from Italy) with diagnosis of severe symptomatic CAVD were used to assess the presence of infiltrating T cells, by cloning approach, and to characterize the valve microbiota, by 16S rRNA gene sequencing (NGS). Results: We documented the presence of infiltrating T lymphocytes, especially the T helper subset, in CAV samples. Moreover, we found a tissue-associated microbiota in freshly collected CAV samples, which was significantly different in Italian and German patients, suggesting potential correlation with other cardiovascular risk factors. Conclusion: The presence of microbiota in inflamed CAV samples represents the right trigger point to explain the valve calcification process, encouraging further studies to explore the potential link between bacteria and adaptive immune response and to define the critical role of local microbiota-immunity axis on CAVD development.

TAVI With or Without Predilation: Trends From a Large, Propensity-Score Weighted German Aortic Valve Registry (GARY) Population.

BACKGROUND AND AIMS: Currently, it is unclear whether transcatheter aortic valve implantation (TAVI) without predilation (direct TAVI; d-TAVI) or with preimplantation balloon valvuloplasty (b-TAVI) provides similar clinical safety and efficacy. Therefore, we analyzed patients undergoing d-TAVI or b-TAVI for severe aortic stenosis (AS) with either self-expanding or balloon-expandable transcatheter heart valves (THVs) from the German Aortic Valve Registry (GARY). METHODS: Between 2011 and 2017, a total of 44,783 TAVI patients were collected, with 25,717 (57.4%) receiving a balloon-expandable THV and 19,066 (42.6%) receiving a self-expanding THV. A propensity-score weighted model was used to compare d-TAVI vs b-TAVI regarding differences in outcome. RESULTS: B-TAVI was performed in 71% and d-TAVI was performed in 29% of patients. In the investigated time interval, frequency of b-TAVI declined from 88.4% to 58.2%, accompanied by a constant rate of postdilation. After propensity weighting of patients receiving balloon-expandable THV, d-TAVI vs b-TAVI was associated with more frequent postoperative transvalvular mean pressure gradients (mPG) >15 mm Hg (20.7% vs 18.4%; P<.001), similar rates of paravalvular leakage (PVL) ≥ moderate (18.0% vs 16.9%; P=.08), fewer postdilations (13.4% vs 15.5%; P<.001), and fewer complications (permanent pacemaker implantation, 10.2% vs 11.9% [P=.01]; vascular complications, 1.9% vs 2.6% [P<.01]; pericardial tamponade, 0.5% vs 0.9% [P<.01]; and stroke, 0.9% vs 1.3% [P=.02]). In patients receiving self-expanding THVs, d-TAVI vs b-TAVI was associated with more frequent postimplantation mean PG ≥ 15 mm Hg (12.7% vs 10.4%; P<.01), higher rates of PVL ≥ moderate (24.8% vs 16.5%; P<.001), and similar complication rates including permanent pacemaker implantation. CONCLUSIONS: The safety and efficacy of d-TAVI vs b-TAVI depends on the type of THV implanted. For balloon-expandable valves, d-TAVI provides an advantage, while self-expanding valves offer a similar safety profile for d-TAVI compared with b-TAVI. However, increased mPG post intervention with both valve types and more significant PVL in self-expanding THVs emphasize the importance of proper patient selection and evaluation of valve anatomy to identify suitable cases for d-TAVI.

Concomitant mitral regurgitation in patients with low-gradient aortic stenosis: an analysis from the German Aortic Valve Registry.

BACKGROUND: Patients with severe aortic stenosis (AS) frequently presented mitral regurgitation (MR), which may interfere with the standard echocardiographic measurements of mean pressure gradient (MPG), flow velocity, and aortic valve area (AVA). AIMS: Herein we investigated the prevalence and severity of MR in patients with severe AS and its role on the accuracy of the standard echocardiographic parameters of AS quantification. METHODS: Of all patients with severe AS undergoing transcatheter or surgical aortic valve replacement enrolled in the German Aortic Registry from 2011 to 2017, 119,641 were included in this study. The population was divided based on the values of left ventricular ejection fraction ([LVEF] > 50%, LVEF 31-50%, and LVEF ≤ 30%] and AVA (0.80 to ≤ 1.00 cm2, 0.60 to < 0.80 cm2, 0.40 to < 0.60 cm2, and 0.20 to < 0.40 cm2). RESULTS: Overall, 77,890 (65%) patients with mild to-moderate and 4262 (4%) with severe MR were compared with 37,489 (31%) patients without MR. Patients with mild-to-moderate and severe MR presented significantly lower mPG (ΔmPG [95%CI] - 1.694 mmHg [- 2.123 to - 1.265], p < 0.0001 and - 6.954 mmHg [- 7.725 to - 6.183], p < 0.0001, respectively), that increased with LVEF impairment. Conversely, AVA did not differ (severe versus no MR: ΔAVA [95%CI]: - 0.007cm2 [- 0.023 to 0.009], p = 0.973). Increasing MR severity was associated with significant mPG reduction throughout all AVA strata, causing a low-gradient pattern, that manifested since the early stages of severe AS (LVEF > 50%: AVA 0.80 to 1.00 cm2; LVEF 31-50%: AVA 0.60 to 0.80 cm2). CONCLUSIONS: In patients with severe AS, concomitant MR is common, contributes to the onset of a low-gradient AS pattern, and affects the diagnostic accuracy of flow-dependent AVA measurements. In this setting, a multimodality, AVA-centric approach should be implemented. In patients with severe aortic stenosis, concomitant mitral regurgitation contributes to the onset of a low-gradient pattern, warranting a multimodality, and AVA-centric diagnostic approach.

Comparison of PCWP and LVEDP Measurements in Patients with Severe Aortic Stenosis Undergoing TAVI-Same Same but Different?

BACKGROUND: Pulmonary capillary wedge pressure (PCWP) and left ventricular end-diastolic pressure (LVEDP) are often used as equivalents for determination of pulmonary hypertension (PH). PH is a comorbidity in patients with severe aortic valve stenosis (AS) and associated with limited prognosis. The aim of the study was to examine the role of differentiated classification basis of PCWP and LVEDP in patients planning for transcatheter aortic valve implantation (TAVI). METHODS: 284 patients with severe AS completed a combined left (LHC) and right heart catheterization (RHC) as part of a TAVI planning procedure. Patients were categorized twice into subtypes of PH according to 2015 European Society of Cardiology (ESC) guidelines-on the one hand with PCWP and on the other hand with LVEDP as classification basis. PCWP-LVEDP relationships were figured out using Kaplan-Meier curves, linear regressions and Bland-Altman analysis. RESULTS: Regarding 1-year mortality, Kaplan-Meier analyses showed similar curves in spite of different classification bases of PH subtypes according to PCWP or LVEDP with exception of pre-capillary PH subtype. PCWP-LVEDP association in the overall cohort was barely present (R = 0.210, R2 = 0.044). When focusing analysis on PH patients only a slightly increased linear regression was noted compared to the overall cohort (R = 0.220, R2 = 0.048). The strongest regression was observed in patients with creatinine ≥ 132 µmol/L (R = 0.357, R2 = 0.127) and in patients with mitral regurgitation ≥ II° (R = 0.326, R2 = 0.106). CONCLUSIONS: In patients with severe AS, there is a weak association between hemodynamic parameters measured by LHC and RHC. RHC measurements alone are not suitable for risk stratification with respect to one-year mortality. If analysis of hemodynamic parameters is necessary in patients with severe AS scheduled for TAVI, measurement results of LHC and RHC should be combined and LVEDP could serve as a helpful indicator for risk assessment.

Computed tomography predictors of structural valve degeneration in patients undergoing transcatheter aortic valve implantation with balloon-expandable prostheses.

OBJECTIVES: Computed tomography (CT) provides excellent anatomy assessment of the aortic annulus (AoA) and is utilized for pre-procedural planning of transcatheter aortic valve implantation (TAVI). We sought to investigate if geometrical characteristics of the AoA determined by CT may represent predictors of structural valve degeneration (SVD) in patients undergoing TAVI with balloon-expandable valves. METHODS: This is a retrospective study on 124 consecutive patients (mean age: 79 ± 7 years; female: 61%) undergoing balloon-expandable TAVI prospectively enrolled in a registry. AoA maximum diameter (Dmax), minimum diameter (Dmin), and area were assessed using pre-procedural CT. SVD was identified during follow-up with transthoracic echocardiography documenting structural prosthetic valve abnormalities with or without hemodynamic changes. RESULTS: The mean follow-up was 5.9 ± 1.7 years. SVD was found in 48 out of 124 patients (38%). AoA Dmax, Dmin, and area were significantly smaller in patients with SVD compared to patients without SVD (25.6 ± 2.2 mm vs. 27.1 ± 2.8 mm, p = 0.012; 20.5 ± 2.1 mm vs. 21.8 ± 2.1 mm, p = 0.001 and 419 ± 77 mm2 vs. 467 ± 88 mm2, p = 0.002, respectively). At univariable analysis, female sex, BSA, 23-mm prosthetic valve size, Dmax < 27.1 mm, and a Dmin < 19.9 mm were associated with SVD, whereas at multivariable analysis, only Dmin < 19.9 mm (OR = 2.873, 95% CI: 1.191-6.929, p = 0.019) and female sex (OR = 2.659, 95% CI: 1.095-6.458, p = 0.031) were independent predictors of SVD. CONCLUSIONS: Female sex and AoA Dmin < 19.9 mm are associated with SVD in patients undergoing TAVI with balloon-expandable valves. When implanting large prostheses in order to avoid paraprosthetic regurgitation, caution should be observed due to the risk of excessive stretching of the AoA Dmin, which may play a role in SVD. KEY POINTS: • Long-term durability is a concern for transcatheter aortic valve bioprosthesis. • CT provides an excellent assessment of the aortic annulus's geometrical characteristics for prosthesis sizing before transcatheter aortic valve implantation (TAVI). • Female sex and a small minimum aortic annulus diameter measured with CT are independent predictors of structural valve degeneration in patients undergoing TAVI with balloon-expandable valves.

Recommendations in pre-procedural imaging assessment for transcatheter aortic valve implantation intervention: Italian Society of Cardiology (SIC)-Italian Society of Medical and Interventional Radiology (SIRM) position paper part 1 (Clinical Indication and Basic Technical Aspects, Heart Team, Role of Echocardiography).

Non-invasive cardiovascular imaging owns a pivotal role in the preoperative assessment of patients for transcatheter aortic valve implantation (TAVI), providing a wide range of crucial information to select the patients who will benefit the most and have the procedure done safely. Although advanced cardiac imaging with cardiac computed tomography is routinely used for a detailed anatomic assessment before TAVI, echocardiography remains the first imaging modality to assess aortic stenosis severity and to provide essential functional information. This document results from the collaboration between the Italian Society of Cardiology (SIC) and the Italian Society of Medical and Interventional Radiology (SIRM), aiming to produce an updated consensus statement about the pre-procedural imaging assessment in patient for TAVI. The writing committee is composed of radiologists and cardiologists, experts in the field of cardiac imaging and structural heart diseases. Part 1 of the document, after a brief overview of the clinical indication and basic technical aspects of TAVI, will focus on the role of echocardiography in TAVI pre-procedural planning.

Recommendations in pre-procedural imaging assessment for TAVI intervention: SIC-SIRM position paper part 2 (CT and MR angiography, standard medical reporting, future perspectives).

Non-invasive cardiovascular imaging owns a pivotal role in the preoperative assessment of patient candidates for transcatheter aortic valve implantation (TAVI), providing a wide range of crucial information to select the patients who will benefit the most and have the procedure done safely. This document has been developed by a joined group of experts of the Italian Society of Cardiology and the Italian Society of Medical and Interventional Radiology and aims to produce an updated consensus statement about the pre-procedural imaging assessment in candidate patients for TAVI intervention. The writing committee consisted of members and experts of both societies who worked jointly to develop a more integrated approach in the field of cardiac and vascular radiology. Part 2 of the document will cover CT and MR angiography, standard medical reporting, and future perspectives.

Cerebral embolisation during transcatheter edge-to-edge repair of the mitral valve with the MitraClip system: a prospective, observational study.

BACKGROUND: New ischaemic brain lesions on magnetic resonance imaging (MRI) are reported in up to 86% of patients after transcatheter edge-to-edge repair of the mitral valve (TEER-MV). Knowledge of the exact procedural step(s) that carry the highest risk for cerebral embolisation may help to further improve the procedure. AIMS: The aim of this study was to identify the procedural step(s) that are associated with an increased risk of cerebral embolisation during TEER-MV with the MitraClip system. Furthermore, the risk of overt stroke and silent brain ischaemia after TEER-MV was assessed. METHODS: In this prospective, pre-specified observational study, all patients underwent continuous transcranial Doppler examination during TEER-MV to detect microembolic signals (MES). MES were assigned to specific procedural steps: (1) transseptal puncture and placement of the guide, (2) advancing and adjustment of the clip in the left atrium, (3) device interaction with the MV, and (4) removal of the clip delivery system and the guide. Neurological examination using the National Institutes of Health Stroke Scale (NIHSS) and cerebral MRI were performed before and after TEER-MV. RESULTS: Fifty-four patients were included. The number of MES differed significantly between the procedural steps with the highest numbers observed during device interaction with the MV. Mild neurological deterioration (NIHSS ≤3) occurred in 9/54 patients. New ischaemic lesions were detected in 21/24 patients who underwent MRI. Larger infarct volume was significantly associated with neurological deterioration. CONCLUSIONS: Cerebral embolisation is immanent to TEER-MV and predominantly occurs during device interaction with the MV. Improvements to the procedure may focus on this procedural step.

High-Sensitivity Cardiac Troponin T in Patients with Severe Chronic Kidney Disease and Suspected Acute Coronary Syndrome.

(1) Background: Patients with severe chronic kidney disease (CKD G4-G5) often have chronically elevated high-sensitivity cardiac troponin T (hs-cTnT) values above the 99th percentile of the upper reference limit. In these patients, optimal cutoff levels for diagnosing non-ST-elevation acute coronary syndrome (NSTE-ACS) requiring revascularization remain undefined. (2) Methods: Of 11,912 patients undergoing coronary angiography from 2012 to 2017 for suspected NSTE-ACS, 325 (3%) had severe CKD. Of these, 290 with available serial hs-cTnT measurements were included, and 300 matched patients with normal renal function were selected as a control cohort. (3) Results: In the CKD cohort, 222 patients (76%) had NSTE-ACS with indication for coronary revascularization. Diagnostic performance was high at presentation and similar to that of the control population (AUC, 95% CI: 0.81, 0.75-0.87 versus 0.85, 0.80-0.89, p = 0.68), and the ROC-derived cutoff value was 4 times higher compared to the conventional 99th percentile. Combining the ROC-derived cutoff levels for hs-cTnT at presentation and absolute 3 h changes, sensitivity increased to 98%, and PPV and NPV improved up to 93% and 86%, respectively. (4) Conclusions: In patients with severe CKD and suspected ACS, the diagnostic accuracy of hs-cTnT for the diagnosis of NSTE-ACS requiring revascularization is improved by using higher assay-specific cutoff levels combined with early absolute changes.

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.

Deoxyribonuclease is prognostic in patients undergoing transcatheter aortic valve replacement.

Degenerative aortic valve stenosis is an inflammatory process that resembles atherosclerosis. Neutrophils release their DNA upon activation and form neutrophil extracellular traps (NETs), which are present on degenerated aortic valves. NETs correlate with pressure gradients in severe aortic stenosis. Transcatheter aortic valve replacement (TAVR) is an established treatment option for aortic valve stenosis. Bioprosthetic valve deterioration promoted by inflammatory, fibrotic and thrombotic processes limits outcome. Deoxyribonuclease is a natural counter mechanism to degrade DNA in circulation. In the present observational study, we investigated plasma levels of double-stranded DNA, deoxyribonuclease activity and outcome after TAVR. 345 consecutive patients undergoing TAVR and 100 healthy reference controls were studied. Double-stranded DNA was measured by fluorescence assays in plasma obtained at baseline and after TAVR. Deoxyribonuclease activity was measured at baseline using single radial enzyme diffusion assays. Follow-up was performed at 12 months, and mean aortic pressure gradient and survival were evaluated. Receiver operating characteristic, Kaplan-Meier curves and Cox regression models were calculated. Baseline double-stranded DNA in plasma was significantly higher compared to healthy controls, was increased at 3 and 7 days after TAVR, and declined thereafter. Baseline deoxyribonuclease activity was decreased compared to healthy controls. Interestingly, low deoxyribonuclease activity correlated with higher C-reactive protein and higher mean transaortic gradient after 12 months. Finally, deoxyribonuclease activity was a strong independent predictor of outcome 12 months after TAVR. Deoxyribonuclease activity is a potential biomarker for risk stratification after TAVR. Pathomechanisms of bioprosthetic valve deterioration involving extracellular DNA and deoxyribonuclease merit investigation.

Outcomes of transcatheter tricuspid valve intervention by right ventricular function: a multicentre propensity-matched analysis.

BACKGROUND: Tricuspid regurgitation (TR) has a poor prognosis and limited treatment options and is frequently accompanied by right ventricular (RV) dysfunction. Transcatheter tricuspid valve interventions (TTVI) to reduce TR have been shown to be safe and feasible with encouraging early results. Patient selection for TTVI remains challenging, with the role of right ventricular (RV) function being unknown. AIMS: The aims of this study were 1) to investigate survival in a TTVI-treated patient population and a conservatively treated TR population, and 2) to evaluate the outcome of TTVI as compared to conservative treatment stratified according to the degree of RV function. METHODS: We studied 684 patients from the multicentre TriValve cohort (TTVI cohort) and compared them to 914 conservatively treated patients from two tertiary care centres. Propensity matching identified 213 pairs of patients with severe TR. As we observed a non-linear relationship of RV function and TTVI outcome, we stratified patients according to tricuspid annular plane systolic excursion (TAPSE) to preserved (TAPSE >17 mm), mid-range (TAPSE 13-17 mm) and reduced (TAPSE <13 mm) RV function. The primary outcome was one-year all-cause mortality. RESULTS: TTVI was associated with a survival benefit in patients with severe TR when compared to matched controls (one-year mortality rate: 13.1% vs 25.8%; p=0.031). Of the three RV subgroups, only in patients with mid-range RV function was TTVI associated with an improved survival (p log-rank 0.004). In these patients, procedural success was associated with a reduced hazard ratio for all-cause mortality (HR 0.22; 95% CI: 0.09, 0.57). CONCLUSIONS: TTVI is associated with reduced mortality compared to conservative therapy and might exert its highest treatment effect in patients with mid-range reduced RV function.

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.

Hypothermia in patients with acute myocardial infarction: a meta-analysis of randomized trials.

BACKGROUND: In patients with acute myocardial infarction (MI) receiving percutaneous coronary intervention (PCI), the role of systemic therapeutic hypothermia remains controversial. We sought to investigate the role of systemic therapeutic hypothermia versus standard of care in patients with acute MI treated with PCI. METHODS: This is a study-level meta-analysis of randomized trials. The primary outcome was all-cause death. The main secondary outcome was infarct size. Other secondary outcomes were recurrent MI, ischemia-driven target vessel revascularization (TVR), major adverse cardiovascular events, and bleeding. RESULTS: A total of 1012 patients with acute MI receiving a PCI in nine trials (503 randomly assigned to hypothermia and 509 to control) were available for the quantitative synthesis. The weighted median follow-up was 30 days. As compared to controls, patients assigned to hypothermia had similar risk of all-cause death (risk ratio, [95% confidence intervals], 1.25 [0.80; 1.95], p = 0.32), with a trend toward higher risk of ischemia-driven TVR (3.55 [0.80; 15.87], p = 0.09) mostly due to acute or subacute stent thrombosis. Although in the overall cohort, infarct size was comparable between groups (standardized mean difference [95% Confidence intervals], 0.06 [- 0.92; 1.04], p = 0.92), patients effectively achieving the protocol-defined target temperature in the hypothermia group had smaller infarct size as compared to controls (p for interaction = 0.016). Treatment strategies did not differ with respect to the other outcomes. CONCLUSIONS: As compared to standard of care, systemic therapeutic hypothermia in acute MI patients treated with PCI provided similar mortality with a signal toward more frequent repeat revascularization. Among patients assigned to hypothermia, those effectively achieving the protocol-defined target temperature displayed smaller infarct size. TRIAL REGISTRATION: PROSPERO, CRD42019138754.

Serum levels of C-terminal FGF23 (cFGF23) are associated with 1-year-mortality in patients undergoing transcatheter aortic valve replacement (TAVR).

INTRODUCTION: Serum levels of FGF23 have been associated with adverse outcomes in cardiovascular diseases in patients with and without impaired renal function. Hence, this study aimed to explore the prognostic relevance of intact FGF23 (iFGF23) and its derivate C-terminal FGF23 (cFGF23) in patients undergoing transcatheter aortic valve replacement (TAVR) with regard to renal function. METHODS: A total of 274 patients undergoing transfemoral TAVR were enrolled in this study. Blood samples were obtained preinterventionally and analyzed for iFGF23 and cFGF23 by means of enzyme linked immunosorbent assay (ELISA). Follow-up was obtained for 12 months. RESULTS: Serum levels of cFGF23 and iFGF23 both correlated positively with serum creatinine and inversely with estimated glomerular filtration rate (eGFR). Cox regression analysis revealed a significant association of cFGF23 with 1-year-mortality in patients with eGFR ≥45ml/min/1.73m², but not in patients with an eGFR <45ml/min/1.73m². A cut-off was calculated for cFGF23 (6.82 pmol/l) and patients with eGFR ≥45ml/min/1.73m² were retrospectively divided into two groups (above/below cut-off). Patients above the cut-off had a significantly worse 1-year-mortality than patients below the cut-off (33.3% vs. 19.6%; OR 2.05 (95%CI 1.03-4.07), p= 0.038). The association of cFGF23 with 1-year-mortality in patients with eGFR ≥45ml/min/1.73m² remained statistically significant even after correction for possible confounders in a multivariate Cox regression analysis. CONCLUSION: cFGF23 could be an individual risk factor for mortality in patients undergoing TAVR with an eGFR ≥45ml/min/1.73m².

Transcatheter Aortic Valve Replacement in Young Low-Risk Patients With Severe Aortic Stenosis: A Review.

In the last decades, transcatheter aortic valve replacement (TAVR) revolutionized the treatment of symptomatic severe aortic stenosis. The efficacy and safety of TAVR were first proven in inoperable and high-risk patients. Then, subsequent randomized clinical trials showed non-inferiority of TAVR as compared to surgical aortic valve replacement also in intermediate- and low-risk populations. As TAVR was progressively studied and clinically used in lower-risk patients, issues were raised questioning its opportunity in a younger population with a longer life-expectancy. As long-term follow-up data mainly derive from old studies with early generation devices on high or intermediate surgical risk patients, results can hardly be extended to most of currently treated patients who often show a low surgical risk and are treated with newer generation prostheses. Thus, in this low-risk younger population, decision making is difficult due to the lack of supporting data. The aim of the present review is to revise current literature regarding TAVR in younger patients.

Transcatheter tricuspid valve repair in the setting of heart failure with preserved or reduced left ventricular ejection fraction.

AIMS: Severe tricuspid regurgitation (TR) impairs prognosis in patients with left-sided heart failure (HF) with preserved (≥50%, HFpEF) and reduced ejection fraction (<50%, HFrEF). Transcatheter tricuspid valve edge-to-edge repair (TTVR) potentially improves prognosis among patients with severe TR. We sought to assess the impact of left-sided HF types on outcomes of TTVR. METHODS AND RESULTS: In this retrospective study, 71 HFpEF and 40 HFrEF patients, defined according to the European Society of Cardiology criteria, with isolated TR treated by TTVR in two tertiary care centres between 2016 and 2019 were analysed. The primary outcome was a composite outcome of all-cause mortality and HF hospitalization at 12 months [median follow-up 238 (interquartile range 175-365) days]. Additionally, a propensity score matching with a conservatively treated cohort of 914 patients with severe TR was performed. Procedural success did not differ between HFpEF (mean age 75.9 ± 9.3 years) or HFrEF (mean age 74.7 ± 9.1 years) patients (86% vs. 78%, P = 0.299). The primary endpoint occurred more frequently in patients with HFrEF as compared to HFpEF (50% vs. 30%, P = 0.016). Procedural success was associated with a reduced occurrence of the primary endpoint among patients with HFpEF (P < 0.001) but not HFrEF (P = 0.813), while both groups showed improvement in New York Heart Association functional class (both P < 0.001). After matching for age, EuroSCORE II, presence of a right ventricular lead and systolic pulmonary artery pressure, successful TTVR was associated with lower mortality as compared to conservative therapy in HFpEF patients (P = 0.020), but not in HFrEF patients (P = 0.274). CONCLUSION: Transcatheter tricuspid valve edge-to-edge repair might be a treatment option in patients with severe TR and HFpEF compared to conservative therapy.