Gene Variants Related to Cardiovascular and Pulmonary Diseases May Correlate with Severe Outcome of COVID-19.

Background: Severe outcomes of COVID-19 account for up to 15% of all cases. The study aims to check if any gene variants related to cardiovascular (CVD) and pulmonary diseases (PD) are correlated with a severe outcome of COVID-19 in a Polish cohort of COVID-19 patients. Methods: In this study, a subset of 747 samples from unrelated individuals collected across Poland in 2020 and 2021 was used and whole-genome sequencing was performed. Results: The GWAS analysis of SNPs and short indels located in genes related to CVD identified one variant significant in COVID-19 severe outcome in the HADHA gene, while for the PD gene panel, we found two significant variants in the DRC1 gene. In this study, both potentially protective and risk variants were identified, of which variants in the HADHA gene deserve the most attention. Conclusions: This is the first study reporting the association between the HADHA and DRC1 genetic variants and COVID-19 severe outcome based on the cohort WGS analysis. Although all the identified variants are localised in introns, they may be correlated and therefore inherited along with other risk variants, potentially causative to severe outcome of COVID-19 but not discovered yet.

The Thousand Polish Genomes-A Database of Polish Variant Allele Frequencies.

Although Slavic populations account for over 4.5% of world inhabitants, no centralised, open-source reference database of genetic variation of any Slavic population exists to date. Such data are crucial for clinical genetics, biomedical research, as well as archeological and historical studies. The Polish population, which is homogenous and sedentary in its nature but influenced by many migrations of the past, is unique and could serve as a genetic reference for the Slavic nations. In this study, we analysed whole genomes of 1222 Poles to identify and genotype a wide spectrum of genomic variation, such as small and structural variants, runs of homozygosity, mitochondrial haplogroups, and de novo variants. Common variant analyses showed that the Polish cohort is highly homogenous and shares ancestry with other European populations. In rare variant analyses, we identified 32 autosomal-recessive genes with significantly different frequencies of pathogenic alleles in the Polish population as compared to the non-Finish Europeans, including C2, TGM5, NUP93, C19orf12, and PROP1. The allele frequencies for small and structural variants, calculated for 1076 unrelated individuals, are released publicly as The Thousand Polish Genomes database, and will contribute to the worldwide genomic resources available to researchers and clinicians.

Properties of Non-Aminoglycoside Compounds Used to Stimulate Translational Readthrough of PTC Mutations in Primary Ciliary Dyskinesia.

Primary ciliary dyskinesia (PCD) is a rare disease with autosomal recessive inheritance, caused mostly by bi-allelic gene mutations that impair motile cilia structure and function. Currently, there are no causal treatments for PCD. In many disease models, translational readthrough of premature termination codons (PTC-readthrough) induced by aminoglycosides has been proposed as an effective way of restoring functional protein expression and reducing disease symptoms. However, variable outcomes of pre-clinical trials and toxicity associated with long-term use of aminoglycosides prompt the search for other compounds that might overcome these problems. Because a high proportion of PCD-causing variants are nonsense mutations, readthrough therapies are an attractive option. We tested a group of chemical compounds with known PTC-readthrough potential (ataluren, azithromycin, tylosin, amlexanox, and the experimental compound TC007), collectively referred to as non-aminoglycosides (NAGs). We investigated their PTC-readthrough efficiency in six PTC mutations found in Polish PCD patients, in the context of cell and cilia health, and in comparison to the previously tested aminoglycosides. The NAGs did not compromise the viability of the primary nasal respiratory epithelial cells, and the ciliary beat frequency was retained, similar to what was observed for gentamicin. In HEK293 cells transfected with six PTC-containing inserts, the tested compounds stimulated PTC-readthrough but with lower efficiency than aminoglycosides. The study allowed us to select compounds with minimal negative impact on cell viability and function but still the potential to induce PTC-readthrough.

Coherent Transfer of Spin Angular Momentum by Evanescent Spin Waves within Antiferromagnetic NiO.

Insulating antiferromagnets have recently emerged as efficient and robust conductors of spin current. Element-specific and phase-resolved x-ray ferromagnetic resonance has been used to probe the injection and transmission of ac spin current through thin epitaxial NiO(001) layers. The spin current is found to be mediated by coherent evanescent spin waves of GHz frequency, rather than propagating magnons of THz frequency, paving the way towards coherent control of the phase and amplitude of spin currents within an antiferromagnetic insulator at room temperature.

Optical field tuning of localized plasmon modes in Ag microcrystals at the nanofemto scale.

Nanoscale plasmonic field enhancement at sub-wavelength metallic particles is crucial for surface sensitive spectroscopy, ultrafast microscopy, and nanoscale energy transduction. Here, we demonstrate control of the spatial distribution of localized surface plasmon modes at sub-optical-wavelength crystalline silver (Ag) micropyramids grown on a Si(001) surface. We employ multiphoton photoemission electron microscopy (mP-PEEM) to image how the plasmonic field distributions vary with the photon energy, light polarization, and phase in coherent two-pulse excitation. For photon energy hυ > 2.0 eV, the mP-PEEM images show single photoemission locus, which splits into a dipolar pattern that straddles the Ag crystal at a lower energy. We attribute the variation to the migration of plasmon resonances from the Ag/vacuum to the Ag/Si interfaces by choice of the photon energy. Furthermore, the dipolar response of the Ag/Si interface follows the polarization state of light: for linearly polarized excitations, the plasmon dipole follows the in-plane electric field vector, while for circularly polarized excitations, it tilts in the direction of the handedness due to the conversion of spin angular momentum of light into orbital angular momentum of the plasmons excited in the sample. Finally, we show the coherent control of the spatial plasmon distribution by exciting the sample with two identical circularly polarized light pulses with delay defined with attosecond precision. The near field distribution wobbles at the pyramid base as the pump-probe delay is advanced due to interferences among the contributing fields. We illustrate how the frequency, polarization, and pulse structure can be used to design and control plasmon fields on the nanofemto scale for applications in chemistry and physics.

Truncating mutations in exons 20 and 21 of OFD1 can cause primary ciliary dyskinesia without associated syndromic symptoms.

BACKGROUND: Primary ciliary dyskinesia (PCD) is a motile ciliopathy, whose symptoms include airway infections, male infertility and situs inversus. Apart from the typical forms of PCD, rare syndromic PCD forms exist. Mutations of the X-linked OFD1 gene cause several syndromic ciliopathies, including oral-facial-digital syndrome type 1, Joubert syndrome type 10 (JBTS10), and Simpson-Golabi-Behmel syndrome type 2, the latter causing the X-linked syndromic form of PCD. Neurological and skeletal symptoms are characteristic for these syndromes, with their severity depending on the location of the mutation within the gene. OBJECTIVES: To elucidate the role of motile cilia defects in the respiratory phenotype of PCD patients with C-terminal OFD1 mutations. METHODS: Whole-exome sequencing in a group of 120 Polish PCD patients, mutation screening of the OFD1 coding sequence, analysis of motile cilia, and magnetic resonance brain imaging. RESULTS: Four novel hemizygous OFD1 mutations, in exons 20 and 21, were found in men with a typical PCD presentation but without severe neurological, skeletal or renal symptoms characteristic for other OFD1-related syndromes. Magnetic resonance brain imaging in two patients did not show a molar tooth sign typical for JBTS10. Cilia in the respiratory epithelium were sparse, unusually long and displayed a defective motility pattern. CONCLUSION: Consistent with the literature, truncations of the C-terminal part of OFD1 (exons 16-22) almost invariably cause a respiratory phenotype (due to motile cilia defects) while their impact on the primary cilia function is limited. We suggest that exons 20-21 should be included in the panel for regular mutation screening in PCD.

Short- and long-term outcomes of alcohol septal ablation for hypertrophic obstructive cardiomyopathy in patients with mild left ventricular hypertrophy: a propensity score matching analysis.

AIMS: Based on European guidelines, alcohol septal ablation (ASA) for hypertrophic obstructive cardiomyopathy (HOCM) is indicated only in patients with interventricular septum (IVS) thickness >16 mm. The aim of this study was to evaluate the short- and long-term outcomes in ASA patients with mild hypertrophy (IVS ≤ 16 mm). METHODS AND RESULTS: We retrospectively evaluated 1505 consecutive ASA patients and used propensity score to match 172 pairs (344 patients) in groups IVS ≤ 16 mm or IVS > 16 mm. There was no occurrence of post-ASA ventriculoseptal defect in the whole cohort (n = 1505). Matched patients had 30-day mortality rate 0% in IVS ≤ 16 mm group and 0.6% in IVS > 16 mm group (P = 1). Patients in IVS ≤ 16 mm group had more ASA-attributable early complications (16% vs. 9%; P = 0.049), which was driven by higher need for pacemaker implantation (13% vs. 8%; P = 0.22). The mean follow-up was 5.4 ± 4.3 years and the annual all-cause mortality rate was 1.8 and 3.2 deaths per 100-patient-years in IVS ≤ 16 group and IVS > 16 group, respectively (log-rank test P = 0.04). There were no differences in symptom relief and left ventricular (LV) gradient reduction. Patients with IVS ≤ 16 mm had less repeated septal reduction procedures (log-rank test P = 0.03). CONCLUSION: Selected patients with HOCM and mild hypertrophy (IVS ≤ 16 mm) had more early post-ASA complications driven by need for pacemaker implantation, but their long-term survival is better than in patients with IVS >16 mm. While relief of symptoms and LV obstruction reduction is similar in both groups, a need for repeat septal reduction is higher in patients with IVS > 16 mm.

Long-term follow-up and safety assessment of angiogenic gene therapy trial VIF-CAD: Transcatheter intramyocardial administration of a bicistronic plasmid expressing VEGF-A165/bFGF cDNA for the treatment of refractory coronary artery disease.

There have been a number of angiogenic gene therapy trials, yielding mixed results as to efficacy, but demonstrating uniform short-term treatment safety. Data regarding long-term safety of angiogenic gene therapy are limited. Double-blind VIF-CAD trial (NCT00620217) assessed myocardial perfusion and clinical data in 52 refractory coronary artery disease (CAD) patients randomized into treatment (VIF; n = 33) and Placebo (n = 19) arms. VIF group received electromechanical system NOGA-guided intramyocardial injections of VEGF-A165/bFGF plasmid (VIF) into ischemic regions, while the Placebo group-placebo plasmid injections. Full 1-year follow-up data have been published. This study presents the results of over 10-year (median 133 months, range 95-149) safety follow-up of VIF-CAD patients. Overall, 12 (36.4%) patients died in VIF and 8 (42.1%) in Placebo group (P = .68). Cardiovascular mortality was 12/33 (36.4%) in the VIF group and 6/19 (31.6%) in Placebo group (P = .73). Two Placebo patients died due to malignancies, but no VIF patients (P = .17). The Kaplan-Meier curves of combined endpoint: cardiovascular mortality, myocardial infarction and stroke were similar for both patient groups (P = .71). Odds ratio of Placebo group increasing (reaching a worse) their CCS class versus VIF was non-significant (OR 1.28, 95% CI = 0.66-2.45; P = .47). However, CCS class improved in time irrespectively of treatment-OR of reaching a less favorable CCS class per each year of follow-up was 0.74 (95% CI 0.685-0.792; P < .0001, pooled data). There were no differences in readmission rates. Intramyocardial VEGF-A165/bFGF plasmid administration appears safe, with no evidence of an increase in the incidence of death, malignancy, myocardial infarction or stroke during 10-year follow-up in this limited patient population.

Advances in therapeutic use of a drug-stimulated translational readthrough of premature termination codons.

Premature termination codons (PTCs) in the coding regions of mRNA lead to the incorrect termination of translation and generation of non-functional, truncated proteins. Translational readthrough of PTCs induced by pharmaceutical compounds is a promising way of restoring functional protein expression and reducing disease symptoms, without affecting the genome or transcriptome of the patient. While in some cases proven effective, the clinical use of readthrough-inducing compounds is still associated with many risks and difficulties. This review focuses on problems directly associated with compounds used to stimulate PTC readthrough, such as their interactions with the cell and organism, their toxicity and bioavailability (cell permeability; tissue deposition etc.). Various strategies designed to overcome these problems are presented.

Concomitant coronary artery disease and its management in patients referred to transcatheter aortic valve implantation: Insights from the POL-TAVI Registry.

BACKGROUND: Coronary artery disease (CAD) and degenerative aortic stenosis often coexist. However, the impact of CAD and its management on the prognosis after transcatheter aortic valve implantation (TAVI) remains uncertain. We sought to evaluate the impact of obstructive CAD, SYNTAX score (Ss), and percutaneous coronary intervention (PCI) prior to TAVI on short-term outcome. METHODS: Overall, 896 patients who underwent TAVI after heart team decision was included. Pre-procedural angiograms were analysed to calculate baseline Ss (bSs) and residual Ss (rSs). Baseline, procedural and follow-up data up to 30 days was acquired from the national POL-TAVI registry. RESULTS: Patients with obstructive CAD at baseline (n = 462, 52%) had higher mortality as compared with the remaining (8.7 vs. 5.1%, log-rank P = 0.039). Also, after correction for confounding factors obstructive CAD was identified as independent predictor of mortality (hazard ratio [HR] 1.74, 95% confidence intervals [CIs] 1.03-2.94, P = 0.037). In obstructive CAD, neither bSs (AUC 0.47, CI 0.38-0.56, P = 0.47) nor rSs (AUC 0.47, CI 0.30-0.64, P = 0.72 for those undergoing PCI and AUC 0.48, CI 0.37-0.59, P = 0.75 for the remaining) was predictive of mortality. When revascularization status was considered, patients with PCI prior to TAVI had similar outcome as those without obstructive CAD at baseline (7.7 vs. 5.1%, log-rank P = 0.23) with no negative impact on mortality (HR 1.13, CI 0.62-2.09, P = 0.69). CONCLUSIONS: In conclusion, obstructive CAD at baseline evaluation for TAVI has independent negative impact on short-term prognosis. However, neither baseline nor residual Ss values have prognostic ability in patients undergoing TAVI. Revascularization prior to TAVI seems to improve survival to levels comparable with patients without obstructive CAD at baseline.

Transcatheter aortic valve-in-valve implantation in failed stentless bioprostheses.

OBJECTIVE: To compare the safety and efficacy of transcathether aortic valve-in-valve implantation (ViV-TAVI) in degenerated stentless bioprostheses with failed stented valves and degenerated native aortic valves. INTRODUCTION: Little is known about ViV-TAVI in degenerated stentless valves. METHODS: Out of 45 ViV-TAVI procedures reported in the POL-TAVI registry, 20 failed stentless valves were compared with 25 stented prostheses and propensity-matched with 45 native TAVI cases. The mean follow-up was 633 (95% confidence interval [CI], 471-795) days and Valve Academic Research Consortium-2 (VARC-2) definitions were applied. RESULTS: Patients with degenerated stentless valves were younger (65.6, CI 58-73.1 years vs 75.6, CI 72.2-78 [stented] vs 80.1, CI 78.7-81.6 y. [native], P < 0.001). Implantation was required later after surgery (11.5, CI 8-14.9 years) in the stentless cohort as compared with the stented one (6.2, CI 4.7-7.6 years, P = 0.006). ViV-TAVI in the stentless group was also associated with larger amount of contrast (211, CI 157-266 mL vs 135, CI 104-167 mL [stented] vs 132 (119-145) mL [native], P = 0.022). Using VARC-2 composite endpoints, ViV-TAVI in stentless prostheses was characterized by a lower device success (50% vs 76% in stented vs 88.9% in native TAVI, P < 0.001), but comparable early safety up to 30 days (73.7% vs 84% vs 81.8%, respectively, log-rank P = 0.667) and long-term clinical efficacy beyond 30 days (72.2% vs 72% vs 73.8%, respectively, log-rank P = 0.963). CONCLUSIONS: Despite technical challenges and a lower device success, ViV-TAVI in stentless aortic bioprostheses achieves similar safety, efficacy, and functional improvement as in stented or degenerated native valves.

Quantification of mitral regurgitation in patients with hypertrophic cardiomyopathy using aortic and pulmonary flow data: impacts of left ventricular outflow tract obstruction and different left ventricular segmentation methods.

BACKGROUND: Cardiovascular magnetic resonance (CMR) imaging in patients with hypertrophic cardiomyopathy (HCM) enables the assessment of not only left ventricular (LV) hypertrophy and scarring but also the severity of mitral regurgitation. CMR assessment of mitral regurgitation is primarily based on the difference between LV stroke volume (LVSV) and aortic forward flow (Ao) measured using the phase-contrast (PC) technique. However, LV outflow tract (LVOT) obstruction causing turbulent, non-laminar flow in the ascending aorta may impact the accuracy of aortic flow quantification, leading to false conclusions regarding mitral regurgitation severity. Thus, we decided to quantify mitral regurgitation in patients with HCM using Ao or, alternatively, main pulmonary artery forward flow (MPA) for mitral regurgitation volume (MRvol) calculations. METHODS: The analysis included 143 prospectively recruited subjects with HCM and 15 controls. MRvol was calculated as the difference between LVSV computed with either the inclusion (LVSVincl) or exclusion (LVSVexcl) of papillary muscles and trabeculations from the blood pool and either Ao (MRvolAoi or MRvolAoe) or MPA (MRvolMPAi or MRvolMPAe). The presence or absence of LVOT obstruction was determined based on Doppler echocardiography findings. RESULTS: MRvolAoi was higher than MRvolMPAi in HCM patients with LVOT obstruction [47.0 ml, interquartile range (IQR) = 31.5-60.0 vs. 35.5 ml, IQR = 26.0-51.0; p < 0.0001] but not in non-obstructive HCM patients (23.0 ml, IQR = 16.0-32.0 vs. 24.0 ml, IQR = 15.3-32.0; p = 0.26) or controls (18.0 ml, IQR = 14.3-21.8 vs. 20.0 ml, IQR = 14.3-22.0; p = 0.89). In contrast to controls and HCM patients without LVOT obstruction, in HCM patients with LVOT obstruction, aortic flow-based MRvol (MRvolAoi) was higher than pulmonary-based findings (MRvolMPAi) (bias = 9.5 ml; limits of agreement: -11.7-30.7 with a difference of 47 ml in the extreme case). The differences between aortic-based and pulmonary-based MRvol values calculated using LVSVexcl mirrored those derived using LVSVincl. However, MRvol values calculated using LVSVexcl were lower in all the groups analyzed (HCM with LVOT obstruction, HCM without LVOT obstruction, and controls) and with all methods of MRvol quantification used (p ≤ 0.0001 for all comparisons). CONCLUSIONS: In HCM patients, LVOT obstruction significantly affects the estimation of aortic flow, leading to its underestimation and, consequently, to higher MRvol values than those obtained with MPA-based MRvol calculations.

Is Transcatheter Tricuspid Valve-In-Valve Implantation Feasible in the Presence of Right Atrial Thrombus?

The case is reported of a successful transcatheter implantation of an Edwards SAPIEN 3 valve (29 mm) into a failing tricuspid bioprosthesis (Sorin Pericarbon, 31 mm). The procedure was performed in a 69-year-old woman with post-rheumatic mitral and tricuspid valve disease. Multiple previous cardiac surgeries precluded the use of another surgical approach. A large, organized, two-piece thrombus in the enlarged right atrium was not considered an absolute contraindication to the procedure. The SAPIEN 3 valve was implanted under general anesthesia, via a femoral venous access, under three-dimensional transesophageal echocardiography guidance. Postoperatively, the systolic right ventricular pressure was increased from 35 to 52 mmHg, but good function of the implanted valve was confirmed with transthoracic echocardiography. The clinical outcome was favorable and the patient was discharged home 72 h after the intervention. Video 1: Transthoracic echocardiography. Tricuspid color Doppler flow after the procedure. Video 2: Fluoroscopy. Fully expanded Edwards SAPIEN 3 valve in the tricuspid position. Video 3: Fluoroscopy. Expansion of the Edwards SAPIEN 3 valve on the balloon. Video 4: Fluoroscopy. Introduction of the Edwards SAPIEN 3 valve into the right atrium. Video 5: Transthoracic echocardiography. Tricuspid color Doppler flow before the procedure.

Long-term clinical outcome after alcohol septal ablation for obstructive hypertrophic cardiomyopathy: results from the Euro-ASA registry.

AIMS: The first cases of alcohol septal ablation (ASA) for obstructive hypertrophic cardiomyopathy (HCM) were published two decades ago. Although the outcomes of single-centre and national ASA registries have been published, the long-term survival and clinical outcome of the procedure are still debated. METHODS AND RESULTS: We report long-term outcomes from the as yet largest multinational ASA registry (the Euro-ASA registry). A total of 1275 (58 ± 14 years, median follow-up 5.7 years) highly symptomatic patients treated with ASA were included. The 30-day post-ASA mortality was 1%. Overall, 171 (13%) patients died during follow-up, corresponding to a post-ASA all-cause mortality rate of 2.42 deaths per 100 patient-years. Survival rates at 1, 5, and 10 years after ASA were 98% (95% CI 96-98%), 89% (95% CI 87-91%), and 77% (95% CI 73-80%), respectively. In multivariable analysis, independent predictors of all-cause mortality were age at ASA (P < 0.01), septum thickness before ASA (P < 0.01), NYHA class before ASA (P = 0.047), and the left ventricular (LV) outflow tract gradient at the last clinical check-up (P = 0.048). Alcohol septal ablation reduced the LV outflow tract gradient from 67 ± 36 to 16 ± 21 mmHg (P < 0.01) and NYHA class from 2.9 ± 0.5 to 1.6 ± 0.7 (P < 0.01). At the last check-up, 89% of patients reported dyspnoea of NYHA class ≤2, which was independently associated with LV outflow tract gradient (P < 0.01). CONCLUSIONS: The Euro-ASA registry demonstrated low peri-procedural and long-term mortality after ASA. This intervention provided durable relief of symptoms and a reduction of LV outflow tract obstruction in selected and highly symptomatic patients with obstructive HCM. As the post-procedural obstruction seems to be associated with both worse functional status and prognosis, optimal therapy should be focused on the elimination of LV outflow tract gradient.

Aminoglycoside-stimulated readthrough of premature termination codons in selected genes involved in primary ciliary dyskinesia.

Translational readthrough of premature termination codons (PTCs) induced by pharmacological compounds has proven to be an effective way of restoring functional protein expression and reducing symptoms in several genetic disorders. We tested the potential of different concentrations of several aminoglycosides (AAGs) for promoting PTC-readthrough in 5 genes involved in the pathogenesis of primary ciliary dyskinesia, an inherited disorder caused by the dysfunction of motile cilia and flagella. The efficiency of readthrough stimulation of PTCs cloned in dual reporter vectors was examined in 2 experimental settings: in vitro (transcription/translation system) and ex vivo (transiently transfected epithelial cell line). PTC-readthrough was observed in 5 of the 16 mutations analyzed. UGA codons were more susceptible to AAG-stimulated readthrough than UAG; no suppression of UAA was observed. The efficiency of PTC-readthrough in vitro (from less than 1% to ∼28% of the translation from the corresponding wild-type constructs) differed with the AAG type and concentration, and depended on the combination of AAG and PTC, indicating that each PTC has to be individually tested with a range of stimulating compounds. The maximal values of PTC suppression observed in the ex vivo experiments were, depending on AAG used, 3-5 times lower than the corresponding values in vitro, despite using AAG concentrations that were 2 orders of magnitude higher. This indicates that, while the in vitro system is sufficient to examine the readthrough-susceptibility of PTCs, it is not sufficient to test the compounds potential to stimulate PTC-readthrough in the living cells. Most of the tested compounds (except for G418) at their highest concentrations did not disturb ciliogenesis in the cultures of primary respiratory epithelial cells from healthy donors.

Translational readthrough potential of natural termination codons in eucaryotes--The impact of RNA sequence.

Termination of protein synthesis is not 100% efficient. A number of natural mechanisms that suppress translation termination exist. One of them is STOP codon readthrough, the process that enables the ribosome to pass through the termination codon in mRNA and continue translation to the next STOP codon in the same reading frame. The efficiency of translational readthrough depends on a variety of factors, including the identity of the termination codon, the surrounding mRNA sequence context, and the presence of stimulating compounds. Understanding the interplay between these factors provides the necessary background for the efficient application of the STOP codon suppression approach in the therapy of diseases caused by the presence of premature termination codons.

Early outcomes of alcohol septal ablation for hypertrophic obstructive cardiomyopathy: a European multicenter and multinational study.

BACKGROUND: This study was designed to evaluate the outcomes of alcohol septal ablation (ASA) under multicenter and multinational conditions. METHODS: Data for 459 patients (age 57 ± 13 years) from nine European centers were prospectively collected and retrospectively analyzed. RESULTS: ASA led to a significant reduction in outflow gradient (PG) and dyspnea [median of PG from 88 (58-123) mm Hg to 21 (11-41) mm Hg; median of NYHA class from 3 (2-3) to 1 (1-2); P < 0.01]. The incidence of 3-month major adverse events (death, electrical cardioversion for tachyarrhythmias, resuscitation) and mortality was 2.8% and 0.7%, respectively. Permanent pacemakers for post-ASA complete heart block were implanted in 43 patients (9%). Multivariate analysis identified higher amount of alcohol (however, in generally low-dose procedures), higher baseline left ventricular ejection fraction and higher age as independent predictors of PG decrease ≥50%. CONCLUSIONS: The results of the first European multicenter and multinational study demonstrate that real-world early outcomes of ASA patients are better than was reported in observations from the first decade after ASA introduction.

Second transcatheter aortic valve implantation for treatment of suboptimal function of previously implanted prosthesis: review of the literature.

OBJECTIVES: To systematically review reported cases of second transcatheter aortic valve deployment within a previously implanted prosthesis (TAV-in-TAV). BACKGROUND: TAV-in-TAV deployment is one of the rescue strategies undertaken due to an unsuccessful or suboptimal transcatheter aortic valve implantation (TAVI) result. Currently, there are no clear indications for second valve implantation and outcomes of patients with 2 prostheses deployed remain poorly known. METHODS: The MEDLINE and PubMed databases were searched for cases of TAV-in-TAV implantations of aortic valve. RESULTS: Forty-three articles reporting on TAV-in-TAV deployment were included in the review. The most frequently observed indication for second valve implantation was aortic regurgitation (AR) occurring shortly after TAVI. There was a strong dominance of paravalvular over intravalvular AR, with prosthesis malposition being the main underlying cause of TAVI failure (81% of all identified cases). Perioperative echocardiographic images are crucial in identifying causes of failure and helpful in optimal rescue strategy selection. Success rate of TAV-in-TAV implantation varies from 90% to 100% with mortality rate of 0-14.3% at 30 days. Despite similar aortic valve function in follow-up, TAV-in-TAV may be an independent predictor of increased cardiovascular mortality. CONCLUSIONS: TAV-in-TAV implantation is feasible and results in favorable short- and mid-term outcomes in patients with acute failure of TAVI without recourse to open-heart surgery. Further studies are needed to establish algorithm of the management of unsuccessful or suboptimal implantation results.

Vascular complications after transcatheter aortic valve implantation (TAVI): risk and long-term results.

UNLABELLED: Vascular complications are the main safety limitations of transcatheter aortic valve implantation (TAVI). The aim of the study was to assess the incidents, predictors, and the impact of early vascular complications on prognosis after TAVI. This was a single-center analysis of vascular complications related to TAVI. Early vascular complications were defined as incidents within 30 days after TAVI and comprised complications related to transvascular: transfemoral/transsubclavian ,and transapical bioprosthesis implantation. Evaluated risk factors were: (1) clinical characteristics, (2) TAVI route, and (3) center experience. In patients with transvascular TAVI the impact of: (1) diameters of access arteries, vascular sheathes and difference between them, (2) arterial wall calcification, and (3) ProStar devices used for access site closure were assessed. Arterial wall calcification and arteries diameters were measured by 64-slice computer tomography. Arterial wall calcification was graded according to 5° scale. RESULTS: between 2009-2011; follow-up 1-23 months (12 ± 15.55), 83 consecutive patients, and 62-91 (81.10 ± 7.20) years, underwent TAVI: 67 (80.72%) patients had transvascular, and 16 (19.27%) patients had transapical bioprosthesis implantation. We noted 44 (53.01%) early vascular complications: 17 (20.48%) were major and 27 (32.53%) were minor incidents. Independent predictors of early vascular complications were: history of anaemia (OR 3.497: 95% CI [1.276-9.581]; p = 0.014), diabetes (OR 0.323: 95% CI [0.108-0.962]; p = 0.042), percutaneous coronary intervention performed as preparation for TAVI (OR 4.809: 95 % CI [1.172-19.736]; p = 0.029), and arterial wall calcification (OR 1.945: 95% CI [1.063-3.558]; p = 0.03). Of 6 (7.22%) in-hospital and 10 (12.98%) late deaths: 5 (83.33%) patients and 8 (80%) patients respectively had post-procedural vascular complications. Vascular complications, which occurred in 30-days after TAVI, predict late mortality (p = 0.036). Conclusions derived were: (1) TAVI patients with history of anaemia and diabetes required careful monitoring for early vascular complications. (2) If coronary intervention before TAVI is required, it should be performed in the time allowing vascular injuries to heal. (3) Calcification of access arteries is an independent predictor of post-procedural vascular complications; therefore, its estimation should be a regular element of preceding computer tomography. (4) Vascular complications seem to be predictors of late mortality after TAVI.

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.