Transcatheter Intervention for Inoperable Tricuspid Surgical Prosthesis Dysfunction: Minimally Invasive Approach to Mitigate Heart Failure.

What is the efficacy and safety of transcatheter tricuspid valve-in-valve implantation for patients with inoperable tricuspid surgical prosthesis dysfunction? Thirty-day mortality after greatly effective transcatheter treatment is 2 times less than the estimated surgical risk.

Tricuspid valve disease and cardiac implantable electronic devices.

The role of cardiac implantable electronic device (CIED)-related tricuspid regurgitation (TR) is increasingly recognized as an independent clinical entity. Hence, interventional TR treatment options continuously evolve, surgical risk assessment and peri-operative care improve the management of CIED-related TR, and the role of lead extraction is of high interest. Furthermore, novel surgical and interventional tricuspid valve treatment options are increasingly applied to patients suffering from TR associated with or related to CIEDs. This multidisciplinary review article developed with electrophysiologists, interventional cardiologists, imaging specialists, and cardiac surgeons aims to give an overview of the mechanisms of disease, diagnostics, and proposes treatment algorithms of patients suffering from TR associated with CIED lead(s) or leadless pacemakers.

Valve-in-valve transcatheter transfemoral mitral valve implantation (ViV-TMVI): Characteristics and early results from nationwide registry.

BACKGROUND: Valve-in-valve transcatheter transfemoral mitral valve implantation (ViV-TMVI) is an emerging treatment alternative to reoperation in high surgical risk patients with a failed mitral bioprostheses. AIM: To describe characteristics and evaluate 30-day outcomes of ViV-TMVI in the Polish population. METHODS: Nationwide registry was initiated to collect data of all patients with failed mitral bioprosthesis undergoing ViV-TMVI in Poland. This study presents 30-days clinical and echocardiographic follow-up. RESULTS: Overall, 27 ViV-TMVI were performed in 8 centers until May 2022 (85% since 2020). Mean (standard deviation [SD]) age was 73 (11.6) years with the median (interquartile range [IQR]) STS score of 5.3% (4.3%-14.3%). Mean (SD) time between surgical implantation and ViV-TMVI was 8.2 (3.2) years. Failed Hancock II (29%) and Perimount Magna (22%) were most frequently treated. Mechanisms of failure were equally often pure mitral regurgitation or stenosis (both 37%) with mixed etiology in 26%. Balloon-expandable Sapien 3/Ultra were used in all but 1 patient. Technical success was 96.3% (1 patient required additional prosthesis). Mean (SD) transvalvular mitral gradient reached 6.7 (2.2) mm Hg and mitral valve area was 1.8 (0.4) cm². None of the patients had moderate or severe mitral regurgitation with only 14.8% graded as mild. In 92.6% device success (2 patients had mean gradient ≥10 mm Hg) and in 85.6% procedural success was present. There were no deaths, cerebrovascular events or need for mitral valve surgery during 30-day follow-up. CONCLUSIONS: In short-term observation ViV-TMVI is safe and effective alternative for patients with failed mitral bioprosthesis at high surgical risk of re-operation. Longer observations on larger sample are warranted.

FGFR1-4 RNA-Based Gene Alteration and Expression Analysis in Squamous Non-Small Cell Lung Cancer.

While fibroblast growth factor receptors (FGFRs) are involved in several biological pathways and FGFR inhibitors may be useful in the treatment of squamous non-small cell lung cancer (Sq-NSCLC), FGFR aberrations are not well characterized in Sq-NSCLC. We comprehensively evaluated FGFR expression, fusions, and variants in 40 fresh-frozen primary Sq-NSCLC (stage IA3−IV) samples and tumor-adjacent normal tissues using real-time PCR and next-generation sequencing (NGS). Protein expression of FGFR1−3 and amplification of FGFR1 were also analyzed. FGFR1 and FGFR4 median gene expression was significantly (p < 0.001) decreased in tumors compared with normal tissue. Increased FGFR3 expression enhanced the recurrence risk (hazard ratio 4.72, p = 0.029), while high FGFR4 expression was associated with lymph node metastasis (p = 0.036). Enhanced FGFR1 gene expression was correlated with FGFR1 protein overexpression (r = 0.75, p = 0.0003), but not with FGFR1 amplification. NGS revealed known pathogenic FGFR2,3 variants, an FGFR3::TACC3 fusion, and a novel TACC1::FGFR1 fusion together with FGFR1,2 variants of uncertain significance not previously reported in Sq-NSCLC. These findings expand our knowledge of the Sq-NSCLC molecular background and show that combining different methods increases the rate of FGFR aberrations detection, which may improve patient selection for FGFRi treatment.

CT in Transcatheter-delivered Treatment of Valvular Heart Disease.

Minimally invasive strategies to treat valvular heart disease have emerged over the past 2 decades. The use of transcatheter aortic valve replacement in the treatment of severe aortic stenosis, for example, has recently expanded from high- to low-risk patients and became an alternative treatment for those with prohibitive surgical risk. With the increase in transcatheter strategies, multimodality imaging, including echocardiography, CT, fluoroscopy, and cardiac MRI, are used. Strategies for preprocedural imaging strategies vary depending on the targeted valve. Herein, an overview of preprocedural imaging strategies and their postprocessing approaches is provided, with a focus on CT. Transcatheter aortic valve replacement is reviewed, as well as less established minimally invasive treatments of the mitral and tricuspid valves. In addition, device-specific details and the goals of CT imaging are discussed. Future imaging developments, such as peri-procedural fusion imaging, machine learning for image processing, and mixed reality applications, are presented.

Functional CAD-RADS using FFRCT on therapeutic management and prognosis in patients with coronary artery disease.

OBJECTIVES: To propose a novel functional Coronary Artery Disease-Reporting and Data System (CAD-RADS) category system integrated with coronary CT angiography (CCTA)-derived fractional flow reserve (FFRCT) and to validate its effect on therapeutic decision and prognosis in patients with coronary artery disease (CAD). METHODS: Firstly, we proposed a novel functional CAD-RADS and evaluated the performance of functional CAD-RADS for guiding treatment strategies with actual clinical treatment as a reference standard in a retrospective multicenter cohort with CCTA and invasive FFR performed in all patients (n = 466). Net reclassification improvement (NRI) of functional CAD-RADS over anatomical CAD-RADS was calculated. Secondly, the prognostic value of functional CAD-RADS in a prospective two-arm cohort (566 [FFRCT arm] vs. 567 [CCTA arm]) was calculated, after a 1-year follow-up, functional CAD-RADS in FFRCT arm (n = 513) and anatomical CAD-RADS in CCTA arm (n = 511) to determine patients at risk of adverse outcomes were compared with a Cox hazard proportional model. RESULTS: Functional CAD-RADS demonstrated superior value over anatomical CAD-RADS (AUC: 0.828 vs. 0.681, p < 0.001) and comparable performance to FFR (AUC: 0.828 vs. 0.848, p = 0.253) in guiding therapeutic decisions. Functional CAD-RADS resulted in the revision of management plan as determined by anatomical CAD-RADS in 30.0% of patients (n = 140) (NRI = 0.369, p < 0.001). Functional CAD-RADS was an independent predictor for 1-year outcomes with indexes of concordance of 0.795 and the corresponding value was 0.751 in anatomical CAD-RADS. CONCLUSION: The novel functional CAD-RADS gained incremental value in guiding therapeutic decision-making compared with anatomical CAD-RADS and comparable power in 1-year prognosis with anatomical CAD-RADS in a real-world scenario. KEY POINTS: • The novel functional CAD-RADS category system with FFRCT integrated into the anatomical CAD-RADS categories was originally proposed. • The novel functional CAD-RADS category system was validated superior value over anatomical CAD-RADS (AUC: 0.828 vs. 0.681, p < 0.001) in guiding therapeutic decisions and revised management plan in 30.0% of patients as determined by anatomical CAD-RADS (net reclassification improvement index = 0.369, p < 0.001). • Functional CAD-RADS was an independent predictor with an index of concordance of 0.795 and 0.751 in anatomical CAD-RADS for 1-year prognosis of adverse outcomes.

Efficacy and safety of coronary computed tomography angiography in patients with a high clinical likelihood of obstructive coronary artery disease.

BACKGROUND: The CAT-CAD trial showed that coronary computed tomography angiography (CTA) in patients with a high prevalence of coronary artery disease (CAD) and indications for invasive coronary angiography (ICA) reduces the number of patients undergoing ICA by two-thirds and nearly eradicates non-actionable ICAs. However, the long-term benefits of this non-invasive strategy remain unknown. AIMS: To evaluate the long-term efficacy and safety of a non-invasive strategy employing coronary CTA vs. ICA as the first-line imaging test in stable patients with a high clinical likelihood of obstruc-tive CAD. METHODS: The long-term outcomes were evaluated for 36 months following randomization and included the efficacy outcome (analyzed as the composite of major adverse cardiovascular events (MACE): all-cause death, acute coronary syndrome, unplanned coronary revascularization, urgent hospitalization for a cardiovascular reason, a stroke) and the safety outcome (analyzed as a cumulative incidence of serious adverse events). RESULTS: One hundred and twenty participants at a mean age of 60.6 (7.9) years (female, 35.0%) were randomized with an allocation ratio of 1:1 to coronary CTA and direct ICA as the first-line anatomical test for suspected obstructive CAD. There were no significant differences between both diagnostic strategies neither in terms of the long-term efficacy (MACE occurrence: 15.5% in coronary CTA group vs. 16.7% in ICA group; log-rank P = 0.89) nor the long-term safety (cumulative number of serious adverse events: 36 vs. 38; P = 0.79, respectively). CONCLUSIONS: Long-term follow-up of the randomized CAT-CAD trial confirms that the strategy employing coronary CTA is an effective and safe, non-invasive, outpatient-based alternative to ICA for patients with a high clinical likelihood of obstructive CAD.

Identifying Patients without a Survival Benefit following Transfemoral and Transapical Transcatheter Aortic Valve Replacement.

Transcatheter aortic valve replacement (TAVR) offers a novel treatment option for patients with severe symptomatic aortic valve stenosis, particularly for patients who are unsuitable candidates for surgical intervention. However, high therapeutical costs, socio-economic considerations, and numerous comorbidities make it necessary to target and allocate available resources efficiently. In the present study, we aimed to identify risk factors associated with futile treatment following transfemoral (TF) and transapical (TA) TAVR. Five hundred and thirty-two consecutive patients (82 ± 9 years, female 63%) who underwent TAVR between June 2009 and December 2016 at the Vienna Heart Center Hietzing were retrospectively analyzed to identify predictors of futility, defined as all-cause mortality at one year following the procedure for the overall patient cohort, as well as the TF and TA cohort. Out of 532 patients, 91 (17%) did not survive the first year after TAVR. A multivariate logistic model identified cerebrovascular disease, home oxygen dependency, wheelchair dependency, periinterventional myocardial infarction, and postinterventional renal replacement therapy as the factors independently associated with an increased one-year mortality. Our findings underscore the significance of a precise preinterventional evaluation, as well as illustrating the subtle differences in baseline characteristics in the TF and TA cohort and their impact on one-year mortality.

Detection of EGFR mutations in liquid biopsy samples using allele-specific quantitative PCR: A comparative real-world evaluation of two popular diagnostic systems.

PURPOSE: The detection of epidermal growth factor receptor (EGFR) mutations in plasma cell-free DNA (cfDNA) is an auxiliary tool for the molecular diagnosis of non-small cell lung cancer (NSCLC), especially when an adequate tumor tissue specimen cannot be obtained. We compared the diagnostic accuracy of two commonly used in vitro diagnostic-certified allele-specific quantitative PCR assays for detecting plasma cfDNA EGFR mutations. METHODS: We analyzed EGFR mutations in plasma cfDNA from 90 NSCLC patients (stages I-IV) before treatment (n â€‹= â€‹60) and after clinical progression on EGFR tyrosine kinase inhibitors (n â€‹= â€‹30) using the cobas EGFR mutation test v2 (Roche Molecular Systems, Inc.) and therascreen EGFR Plasma RGQ PCR kit (Qiagen GmbH). RESULTS: There was higher concordance between plasma cfDNA and matched tumor tissue EGFR mutations with cobas (66.67%) compared with therascreen (55.93%). The concordance rate increased to 90.00% with cobas (Cohen's kappa coefficient, κ â€‹= â€‹0.80; p â€‹< â€‹0.0001) and 73.33% with therascreen (κ â€‹= â€‹0.49; p â€‹= â€‹0.0009) in advanced NSCLC patients. In treatment-naïve patients, cobas was superior to therascreen (sensitivity: 82.35% vs. 52.94%; specificity: 100% vs. 100%). In patients with clinical progression on EGFR tyrosine kinase inhibitors, EGFR exon 20 p.T790M was detected in 30% and 23% of cfDNA samples by cobas and therascreen, respectively. CONCLUSIONS: Cobas was superior to therascreen for detection of plasma EGFR mutations in advanced NSCLC. Plasma cfDNA EGFR mutation analysis is complex; therefore, the diagnostic accuracy of commercially available assays should be validated.

Complex transcatheter aortic valve replacement in aortic regurgitation and transcatheter mitral annuloplasty in severe dextrocardia.

A 70-year-old female with symptomatic severe native aortic regurgitation, acquired dextrocardia, moderate-to-severe secondary mitral regurgitation and prohibitive surgical risk was admitted for transcatheter aortic valve replacement. A balloon-expendable Sapien 3 Ultra valve was implanted successfully. After 6 months, the patient remained symptomatic due to the concomitant moderate-to-severe secondary mitral regurgitation. Transcatheter mitral valve repair using a Carillon Mitral Contour System was performed resulting in a significant reduction of mitral regurgitation and uneventful follow-up. Most importantly, other transcatheter repair techniques would not have been feasible due to the impossible transoesophageal echocardiography guidance. This is the first case of transcatheter aortic valve replacement in a patient with native aortic regurgitation, acquired dextrocardia and severe aortic annulus malrotation using a balloon-expendable valve. Moreover, it is the first transcatheter mitral valve repair procedure using Carillon device performed by a cardiac surgeon.

The Iliofemoral tortuosity score predicts access and bleeding complications during transfemoral transcatheter aortic valve replacement: DataData from the VIenna Cardio Thoracic aOrtic valve registrY (VICTORY).

BACKGROUND: Arterial tortuosity is linked to a higher risk of adverse clinical events after transfemoral transcatheter aortic valve replacement (TF-TAVR). Currently, there are no assessment tools that can quantify this variable in three-dimensional space. This study investigated the impact of novel scoring methods of iliofemoral tortuosity on access and bleeding complications after TF-TAVR. METHODS: The main access vessel was assessed between the aortoiliacal and femoral bifurcation in preoperative multislice computed tomography scans of 240 consecutive patients undergoing TF-TAVR. Tortuosity was assessed by three methods: largest single angle, sum of all angles, and iliofemoral tortuosity (IFT) score [((true vessel length/ideal vessel length)-1)*100]. The primary study endpoint was a composite of access and bleeding complications. The secondary study endpoints were 30-day mortality and long-term survival. RESULTS: Among 240 patients, only the IFT score demonstrated a good positive correlation with the composite primary endpoint of access and bleeding complications (P = 0.031). A higher incidence of access and bleeding complications was found in patients with a higher IFT score (56 [36.8%] vs 17 [19.3%]; P = 0.003). In a multivariate logistic regression analysis, only the IFT score was a significant predictor of the primary endpoint (OR: 2.11; 95% CI: 1.09-4.05; P = 0.026). CONCLUSION: Vascular tortuosity is an underestimated risk factor during TF-TAVR. The IFT score is a valuable tool in risk stratification before TF-TAVR, predicting periprocedural access and bleeding complications.

Validation of Lung EpiCheck, a novel methylation-based blood assay, for the detection of lung cancer in European and Chinese high-risk individuals.

AIM: Lung cancer screening reduces mortality. We aim to validate the performance of Lung EpiCheck, a six-marker panel methylation-based plasma test, in the detection of lung cancer in European and Chinese samples. METHODS: A case-control European training set (n=102 lung cancer cases, n=265 controls) was used to define the panel and algorithm. Two cut-offs were selected, low cut-off (LCO) for high sensitivity and high cut-off (HCO) for high specificity. The performance was validated in case-control European and Chinese validation sets (cases/controls 179/137 and 30/15, respectively). RESULTS: The European and Chinese validation sets achieved AUCs of 0.882 and 0.899, respectively. The sensitivities/specificities with LCO were 87.2%/64.2% and 76.7%/93.3%, and with HCO they were 74.3%/90.5% and 56.7%/100.0%, respectively. Stage I nonsmall cell lung cancer (NSCLC) sensitivity in European and Chinese samples with LCO was 78.4% and 70.0% and with HCO was 62.2% and 30.0%, respectively. Small cell lung cancer (SCLC) was represented only in the European set and sensitivities with LCO and HCO were 100.0% and 93.3%, respectively. In multivariable analyses of the European validation set, the assay's ability to predict lung cancer was independent of established risk factors (age, smoking, COPD), and overall AUC was 0.942. CONCLUSIONS: Lung EpiCheck demonstrated strong performance in lung cancer prediction in case-control European and Chinese samples, detecting high proportions of early-stage NSCLC and SCLC and significantly improving predictive accuracy when added to established risk factors. Prospective studies are required to confirm these findings. Utilising such a simple and inexpensive blood test has the potential to improve compliance and broaden access to screening for at-risk populations.

Non-ST-elevation myocardial infarction after complex percutaneous coronary intervention and transcatheter aortic valve implantation: a case report of bioprosthesis-related delayed coronary obstruction and its difficult diagnosis.

BACKGROUND: There is a high coincidence of significant coronary artery disease and severe aortic stenosis. Coronary revascularization should be performed prior to transcatheter aortic valve implantation (TAVI). We report a case of non-ST-elevation myocardial infarction (NSTEMI) after complex percutaneous coronary intervention (PCI) prior to TAVI, where differential diagnosis between coronary stent failure and bioprosthesis-related sinus obstruction was substantial. CASE SUMMARY: A 79-year-old woman was re-admitted to the hospital 5 days after TAVI due to troponin-negative new-onset angina. She underwent complex PCI 3 days before TAVI and was not compliant to medications. Symptoms initially resolved after re-establishment of anti-hypertensive treatment. There were no signs of aortic bioprosthesis failure, paravalvular leak, or myocardial ischaemia. After 1 month, the symptoms re-occurred. Due to elevated troponins, myocardial ischaemia in electrocardiogram and new contractility disorders, NSTEMI was diagnosed. Because it was impossible to intubate the left coronary artery (LCA), cardiac surgery was performed. Calcified native coronary leaflet was pushed by the stent frame of aortic bioprosthesis towards LCA ostium causing its subtotal occlusion. Transcatheter heart valve (THV) was removed and the new surgical aortic bioprosthesis was implanted. Further hospitalization and 1-month follow-up were uneventful. DISCUSSION: Pre-procedural assessment is crucial prior to THV interventions. Delayed coronary obstruction caused by the native leaflet is extremely rare and potentially fatal complication of TAVI. The diagnosis is difficult and high clinical suspicion is required to detect this pathology. Given our experience, the indication towards interventional or surgical repair should be established faster to avoid coronary ischaemia.