Nonprocedural bleeding after left atrial appendage closure versus direct oral anticoagulants: A subanalysis of the randomized PRAGUE-17 trial.

INTRODUCTION: Observational studies have shown low bleeding rates in patients with atrial fibrillation (AF) treated by left atrial appendage closure (LAAC); however, data from randomized studies are lacking. This study compared bleeding events among patients with AF treated by LAAC and nonvitamin K anticoagulants (NOAC). METHODS: The Prague-17 trial was a prospective, multicenter, randomized trial that compared LAAC to NOAC in high-risk AF patients. The primary endpoint was a composite of a cardioembolic event, cardiovascular death, and major and clinically relevant nonmajor bleeding (CRNMB) defined according to the International Society on Thrombosis and Hemostasis (ISTH). RESULTS: The trial enrolled 402 patients (201 per arm), and the median follow-up was 3.5 (IQR 2.6-4.2) years. Bleeding occurred in 24 patients (29 events) and 32 patients (40 events) in the LAAC and NOAC groups, respectively. Six of the LAAC bleeding events were procedure/device-related. In the primary intention-to-treat analysis, LAAC was associated with similar rates of ISTH major or CRNMB (sHR 0.75, 95% CI 0.44-1.27, p = 0.28), but with a reduction in nonprocedural major or CRNMB (sHR 0.55, 95% CI 0.31-0.97, p = 0.039). This reduction for nonprocedural bleeding with LAAC was mainly driven by a reduced rate of CRNMB (sHR for major bleeding 0.69, 95% CI 0.34-1.39, p = .30; sHR for CRNMB 0.43, 95% CI 0.18-1.03, p = 0.059). History of bleeding was a predictor of bleeding during follow-up. Gastrointestinal bleeding was the most common bleeding site in both groups. CONCLUSION: During the 4-year follow-up, LAAC was associated with less nonprocedural bleeding. The reduction is mainly driven by a decrease in CRNMB.

Transseptal puncture in left atrial appendage closure guided by 3D printing and multiplanar CT reconstruction.

BACKGROUND: The presented study investigates the application of bi-arterial 3D printed models to guide transseptal puncture (TSP) in left atrial appendage closure (LAAC). AIMS: The objectives are to (1) test the feasibility of 3D printing (3DP) for TSP guidance, (2) analyse the distribution of the optimal TSP locations, and (3) define a CT-derived 2D parameter suitable for predicting the optimal TSP locations. METHODS: Preprocedural planning included multiplanar CT reconstruction, 3D segmentation, and 3DP. TSP was preprocedurally simulated in vitro at six defined sites. Based on the position of the sheath, TSP sites were classified as optimal, suboptimal, or nonoptimal. The aim was to target the TSP in the recommended position during the procedure. Procedure progress was assessed post hoc by the operator. RESULTS: Of 68 screened patients, 60 patients in five centers (mean age of 74.68 ± 7.64 years, 71.66% males) were prospectively analyzed (3DP failed in one case, and seven patients did not finally undergo the procedure). In 55 patients (91.66%), TSP was performed in the optimal location as recommended by the 3DP. The optimal locations for TSP were postero-inferior in 45.3%, mid-inferior in 45.3%, and antero-inferior in 37.7%, with a mean number of optimal segments of 1.34 ± 0.51 per patient. When the optimal TSP location was achieved, the procedure was considered difficult in only two (3.6%) patients (but in both due to complicated LAA anatomy). Comparing anterior versus posterior TSP in 2D CCT, two parameters differed significantly: (1) the angle supplementary to the LAA ostium and the interatrial septum angle (160.83° ± 9.42° vs. 146.49° ± 8.67°; p = 0.001), and (2) the angle between the LAA ostium and the mitral annulus (95.02° ± 3.73° vs. 107.38° ± 6.76°; p < 0.001), both in the sagittal plane. CONCLUSIONS: In vitro TSP simulation accurately determined the optimal TSP locations for LAAC and facilitated the procedure. More than one-third of the optimal TSP sites were anterior.

Extracorporeal versus conventional cardiopulmonary resuscitation for refractory out-of-hospital cardiac arrest: a secondary analysis of the Prague OHCA trial.

BACKGROUND: Survival rates in refractory out-of-hospital cardiac arrest (OHCA) remain low with conventional advanced cardiac life support (ACLS). Extracorporeal life support (ECLS) implantation during ongoing resuscitation, a method called extracorporeal cardiopulmonary resuscitation (ECPR), may increase survival. This study examined whether ECPR is associated with improved outcomes. METHODS: Prague OHCA trial enrolled adults with a witnessed refractory OHCA of presumed cardiac origin. In this secondary analysis, the effect of ECPR on 180-day survival using Kaplan-Meier estimates and Cox proportional hazard model was examined. RESULTS: Among 256 patients (median age 58 years, 83% male) with median duration of resuscitation 52.5 min (36.5-68), 83 (32%) patients achieved prehospital ROSC during ongoing conventional ACLS prehospitally, 81 (32%) patients did not achieve prehospital ROSC with prolonged conventional ACLS, and 92 (36%) patients did not achieve prehospital ROSC and received ECPR. The overall 180-day survival was 51/83 (61.5%) in patients with prehospital ROSC, 1/81 (1.2%) in patients without prehospital ROSC treated with conventional ACLS and 22/92 (23.9%) in patients without prehospital ROSC treated with ECPR (log-rank p < 0.001). After adjustment for covariates (age, sex, initial rhythm, prehospital ROSC status, time of emergency medical service arrival, resuscitation time, place of cardiac arrest, percutaneous coronary intervention status), ECPR was associated with a lower risk of 180-day death (HR 0.21, 95% CI 0.14-0.31; P < 0.001). CONCLUSIONS: In this secondary analysis of the randomized refractory OHCA trial, ECPR was associated with improved 180-day survival in patients without prehospital ROSC. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01511666, Registered 19 January 2012.

Feasibility of Brachial Occlusion Technique for Beat-to-Beat Pulse Wave Analysis.

Czech physiologist Penaz tried to overcome limitations of invasive pulse-contour methods (PCM) in clinical applications by a non-invasive method (finger mounted BP cuff) for continuous arterial waveform detection and beat-to-beat analysis. This discovery resulted in significant interest in human physiology and non-invasive examination of hemodynamic parameters, however has limitations because of the distal BP recording using a volume-clamp method. Thus, we propose a validation of beat-to-beat signal analysis acquired by novel a brachial occlusion-cuff (suprasystolic) principle and signal obtained from Finapres during a forced expiratory effort against an obstructed airway (Valsalva maneuver). Twelve healthy adult subjects [2 females, age = (27.2 ± 5.1) years] were in the upright siting position, breathe through the mouthpiece (simultaneously acquisition by brachial blood pressure monitor and Finapres) and at a defined time were asked to generate positive mouth pressure for 20 s (Valsalva). For the purpose of signal analysis, we proposed parameter a "Occlusion Cuff Index" (OCCI). The assumption about similarities between measured signals (suprasystolic brachial pulse waves amplitudes and Finapres's MAP) were proved by averaged Pearson's correlation coefficient (r- = 0.60, p < 0.001). The averaged Pearson's correlation coefficient for the comparative analysis of OCCI between methods was r- = 0.88, p < 0.001. The average percent change of OCCI during maneuver: 8% increase, 19% decrease and percent change of max/min ratio is 35%. The investigation of brachial pulse waves measured by novel brachial blood pressure monitor shows positive correlation with Finapres and the parameter OCCI shows promise as an index, which could describe changes during beat-to-beat cardiac cycles.

Effect of Intra-arrest Transport, Extracorporeal Cardiopulmonary Resuscitation, and Immediate Invasive Assessment and Treatment on Functional Neurologic Outcome in Refractory Out-of-Hospital Cardiac Arrest: A Randomized Clinical Trial.

Importance: Out-of-hospital cardiac arrest (OHCA) has poor outcome. Whether intra-arrest transport, extracorporeal cardiopulmonary resuscitation (ECPR), and immediate invasive assessment and treatment (invasive strategy) is beneficial in this setting remains uncertain. Objective: To determine whether an early invasive approach in adults with refractory OHCA improves neurologically favorable survival. Design, Setting, and Participants: Single-center, randomized clinical trial in Prague, Czech Republic, of adults with a witnessed OHCA of presumed cardiac origin without return of spontaneous circulation. A total of 256 participants, of a planned sample size of 285, were enrolled between March 2013 and October 2020. Patients were observed until death or day 180 (last patient follow-up ended on March 30, 2021). Interventions: In the invasive strategy group (n = 124), mechanical compression was initiated, followed by intra-arrest transport to a cardiac center for ECPR and immediate invasive assessment and treatment. Regular advanced cardiac life support was continued on-site in the standard strategy group (n = 132). Main Outcomes and Measures: The primary outcome was survival with a good neurologic outcome (defined as Cerebral Performance Category [CPC] 1-2) at 180 days after randomization. Secondary outcomes included neurologic recovery at 30 days (defined as CPC 1-2 at any time within the first 30 days) and cardiac recovery at 30 days (defined as no need for pharmacological or mechanical cardiac support for at least 24 hours). Results: The trial was stopped at the recommendation of the data and safety monitoring board when prespecified criteria for futility were met. Among 256 patients (median age, 58 years; 44 [17%] women), 256 (100%) completed the trial. In the main analysis, 39 patients (31.5%) in the invasive strategy group and 29 (22.0%) in the standard strategy group survived to 180 days with good neurologic outcome (odds ratio [OR], 1.63 [95% CI, 0.93 to 2.85]; difference, 9.5% [95% CI, -1.3% to 20.1%]; P = .09). At 30 days, neurologic recovery had occurred in 38 patients (30.6%) in the invasive strategy group and in 24 (18.2%) in the standard strategy group (OR, 1.99 [95% CI, 1.11 to 3.57]; difference, 12.4% [95% CI, 1.9% to 22.7%]; P = .02), and cardiac recovery had occurred in 54 (43.5%) and 45 (34.1%) patients, respectively (OR, 1.49 [95% CI, 0.91 to 2.47]; difference, 9.4% [95% CI, -2.5% to 21%]; P = .12). Bleeding occurred more frequently in the invasive strategy vs standard strategy group (31% vs 15%, respectively). Conclusions and Relevance: Among patients with refractory out-of-hospital cardiac arrest, the bundle of early intra-arrest transport, ECPR, and invasive assessment and treatment did not significantly improve survival with neurologically favorable outcome at 180 days compared with standard resuscitation. However, the trial was possibly underpowered to detect a clinically relevant difference. Trial Registration: ClinicalTrials.gov Identifier: NCT01511666.

Noninvasive Assessment of Aortic Pulse Wave Velocity by the Brachial Occlusion-Cuff Technique: Comparative Study.

Cardiovascular diseases are one of most frequent cause of morbidity and mortality in the world. There is an emerging need for integrated, non-invasive, and easy-to-use clinical tools to assess accurately cardiovascular system primarily in the preventative medicine. We present a novel design for a non-invasive pulse wave velocity (PWV) assessment method integrated in a single brachial blood pressure monitor allowing for up to 100 times more sensitive recording of the pressure pulsations based on a brachial occlusion-cuff (suprasystolic) principle. The monitor prototype with built-in proprietary method was validated with a gold standard reference technique SphygmoCor VX device. The blood pressure and PWV were assessed on twenty-five healthy individuals (9 women, age (37 ± 13) years) in a supine position at rest by a brachial cuff blood pressure monitor prototype, and immediately re-tested using a gold standard method. PWV using our BP monitor was (6.67 ± 0.96) m/s compared to PWV determined by SphygmoCor VX (6.15 ± 1.01) m/s. The correlation between methods using a Pearson's correlation coefficient was r = 0.88 (p < 0.001). The study demonstrates the feasibility of using a single brachial cuff build-in technique for the assessment of the arterial stiffness from a single ambulatory blood pressure assessment.

Interventional left atrial appendage closure vs novel anticoagulation agents in patients with atrial fibrillation indicated for long-term anticoagulation (PRAGUE-17 study).

Atrial fibrillation (AF), with a prevalence of 1% to 2%, is the most common cardiac arrhythmia. Without antithrombotic treatment, the annual risk of a cardioembolic event is 5% to 6%. The source of a cardioembolic event is a thrombus, which is usually formed in the left atrial appendage (LAA). Prevention of cardioembolic events involves treatment with anticoagulant drugs: either vitamin K antagonists or, recently, novel oral anticoagulants (NOAC). The other (nonpharmacologic) option for the prevention of a cardioembolic event involves interventional occlusion of the LAA. OBJECTIVE: To determine whether percutaneous LAA occlusion is noninferior to treatment with NOAC in AF patients indicated for long-term systemic anticoagulation. STUDY DESIGN: The trial will be a prospective, multicenter, randomized noninferiority trial comparing 2 treatment strategies in moderate to high-risk AF patients (ie, patients with history of significant bleeding, or history of cardiovascular event(s), or a with CHA2DS2VASc ≥3 and HAS-BLED score ≥2). Patients will be randomized into a percutaneous LAA occlusion (group A) or a NOAC treatment (group B) in a 1:1 ratio; the randomization was done using Web-based randomization software. A total of 396 study participants (198 patients in each group) will be enrolled in the study. The primary end point will be the occurrence of any of the following events within 24months after randomization: stroke or transient ischemic attack (any type), systemic cardioembolic event, clinically significant bleeding, cardiovascular death, or a significant periprocedural or device-related complications. CONCLUSION: The PRAGUE-17 trial will determine if LAA occlusion is noninferior to treatment with NOAC in moderate- to high-risk AF patients.

Variants in miRNA regulating cardiac growth are not a common cause of hypertrophic cardiomyopathy.

OBJECTIVES: A substantial proportion of patients with hypertrophic cardiomyopathy (HCM) do not have causative mutations in the genes for heart sarcomere. The purpose of this study was to evaluate the association between microRNA (miRNA) sequence variants and HCM. METHODS: We performed genetic testing on 56 HCM patients who had previously been found to be negative for mutations in the 4 major genes for sarcomeric proteins. The coding and adjacent regions (120-220 nt) of selected miRNAs were analyzed for the presence of sequence variants. The testing was based on PCR amplification of DNA-encoding miRNAs and subsequent denaturing capillary electrophoresis. RESULTS: A total of 3 different variants were detected in the 11 selected miRNAs. These included polymorphisms rs45489294 in miRNA 208b, rs13136737 in miRNA 367 and rs9989532 in miRNA 1-2. In the patient group, the most frequent polymorphism was in miRNA 208b (10 times) followed by miRNA 367 (7 times). Both polymorphisms were found to occur with similar frequencies in the group of healthy controls. The remaining detected variant was not present in the control group, but was not connected with the HCM phenotype in the children of the probands. CONCLUSION: Sequence variants in miRNAs of patients with HCM are not frequent and the contribution of these variants to the development of this disease was not demonstrated.

Long-term survival after alcohol septal ablation for hypertrophic obstructive cardiomyopathy: a comparison with general population.

AIMS: We decided to determine the long-term survival of patients after alcohol septal ablation (ASA) for hypertrophic obstructive cardiomyopathy (HOCM) and compare this with the general population. METHODS AND RESULTS: A total of 178 highly symptomatic, consecutive patients (58 ± 12 years, 53% women) were treated by ASA between April 1998 and April 2013 and followed-up for 4.8 years (IQR 2.1-7.5). At baseline, 155 patients (87%) suffered from dyspnoea ≥3 class of NYHA; at the most recent examination, 87 patients (49%) and 23 patients (13%) reported dyspnoea of NYHA class 1 and ≥3, respectively. The left ventricular outflow gradient was significantly reduced (68 ± 42 vs. 20 ± 25 mmHg; P < 0.01). A total of 19 deaths (11%) occurred during 925 patient-years, which means an overall mortality rate of 2.1% per year. Survival free of all-cause mortality at 1, 5, and 10 years was 97% (95% CI, 93-99%), 92% (95% CI, 87-96%), and 82% (95% CI, 70-90%), respectively. This observed mortality was comparable to the expected survival for age- and sex-comparable general population (P = 0.34). According to multivariate analysis, the only independent predictor of all-cause mortality was age at ASA (hazard ratio 1.09, 95% CI 1.04-1.14; P < 0.01). CONCLUSIONS: This study suggests that in patients with HOCM and important symptoms who underwent ASA, long-term survival after the procedure did not differ significantly from that of the general population.

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.

Left ventricular outflow tract obstruction after mitral valve repair treated with alcohol septal ablation.

Left ventricular outflow tract (LVOT) obstruction due to systolic anterior motion of the mitral valve (SAM) occurs in 4-5% of patients after mitral valve repair. If conservative treatment is unsuccessful, reoperation is indicated. Treatment options include repeated mitral valve repair or valve replacement and septal myectomy if hypertrophy is present. We report a case of a patient with pre-operatively undiagnosed hypertrophic cardiomyopathy who suffered from progressive dyspnea post-operation due to severe LVOT obstruction with SAM. This case was successfully treated with catheter-based alcohol septal ablation.

Comparison of long-term effect of dual-chamber pacing and alcohol septal ablation in patients with hypertrophic obstructive cardiomyopathy.

INTRODUCTION: Nonpharmacological treatment of patients with hypertrophic obstructive cardiomyopathy (HOCM) comprises surgical myectomy (SME), alcohol septal ablation (ASA), and dual-chamber (DDD) pacing. The aim of the study was to compare the long-term effect of DDD pacing and ASA in symptomatic HOCM patients. PATIENTS AND METHODS: We evaluated retrospective data from three cardiocenters; there were 24 patients treated with DDD pacing included and 52 treated with ASA followed for 101 ± 49 and 87 ± 23 months, respectively. RESULTS: In the group treated with DDD pacing, the left ventricle outflow tract gradient (LVOTG) decreased from 82 ± 44 mmHg to 21 ± 21 mmHg, and NYHA class improved from 2.7 ± 0.5 to 2.1 ± 0.6 (both P < 0.001). In the ASA-treated group, a decline in LVOTG from 73 ± 38 mmHg to 24 ± 26 mmHg and reduction in NYHA class from 2.8 ± 0.5 to 1.7 ± 0.8 were observed (both P < 0.001). The LVOTG change was similar in both groups (P = 0.264), and symptoms were more affected by ASA (P = 0.001). CONCLUSION: ASA and DDD pacing were similarly effective in reducing LVOTG. The symptoms improvement was more expressed in patients treated with ASA.

Study of the Mineralogical Composition of an Alumina-Silica Binder System Formed by the Sol-Gel Method.

Colloidal bonds are realized by sol-gel technology. The binder system of the refractory castable belongs to the Al2O3-SiO2 binary diagram. Mullite is the most thermally stable mineral in this system. This work was motivated by an attempt to maximize the mullite content in the NCC binder system, because a high content of mullite is a guarantee of the long service life of refractories. Initially, the mineralogical composition of the pure gel was tested after drying and firing at temperatures between 1000 °C and 1600 °C. The behavior of the gel during drying was described. Subsequently, a method of minimizing gel shrinkage during drying was sought. To this aim, fine fillers (microfillers) of alumina and silica were tested. In particular, the reactivity of the microfillers, the ability of the microfillers to react with the sol to form mullite, and the drying shrinkage of the microfiller-doped gel were evaluated. The study showed that the least suitable source of Al2O3 in terms of its reactivity is tabular corundum, which produces the lowest amount of mullite. The internal structure of the prepared binder system when using different microfillers was described. Based on the results from the second stage of the work, several complete matrixes of the binder system were designed and the degree of their mullitization at different firing temperatures was studied. During this stage, it was shown that the degree of mullitization of the binder system depends mainly on the microsilica content. In the binder system, the maximum mullite content recorded was 76%. The effect of amorphous SiO2 on the bulk density and internal structure of the binder system was also described.

Spectrum and clinical manifestations of mutations in genes responsible for hypertrophic cardiomyopathy.

INTRODUCTION: Hypertrophic cardiomyopathy (HCM) is a cardiovascular disease with autosomal dominant inheritance. It is caused by mutations in the genes coding for structural and/or regulatory proteins found in the sarcomere of cardiomyocytes. A group of genes, including the heavy chain of beta-myosin (MYH7), myosin binding protein C (MYBPC3), cardiac troponin I (TNNI3) and cardiac troponin T (TNNT2) are frequently affected by causal mutations. While exact mutation frequency data has been obtained for various populations, no screening has been reported for Central European populations. PATIENTS AND METHODS: We performed a complete sequencing of MYH7, MYBPC3, TNNI3 and TNNT2 genes in 100 HCM patients. RESULTS: We discovered mutations in a total of 40 patients (40%), including 4 patients with double mutations. A total of 35 different mutation types were detected, of which 17 were novel. The contributions from individual genes were: 24 mutations in MYBPC3 (54.5%), 14 in MYH7 (31.8%), 4 in TNNI3 (9%) and 2 mutations in TNNT2 (4.5%). We have observed a wide variability in disease manifestation across the different genes/mutation types. In addition, we have discovered differences in both frequency and distribution of mutations of the two most common genes (MYBPC3 and MYH7) compared to other populations. CONCLUSION: The most common gene responsible for HCM in our study population was MYBPC3, followed by MYH7, TNNI3 and TNNT2. Phenotypic heterogeneity, as well as the dissimilarity to other populations, prevents effective use of a pre-screening test, which would be directed at the most common mutation hotspots, in our population.

Development and Testing of Castables with Low Content of Calcium Oxide.

Colloidal silica is used in many kinds of industry. It is an aqueous dispersion of SiO2 nanoparticles. SiO2 colloidal solutions are commercially available in different concentrations, with different particle sizes and are stabilized with different ions. Colloidal SiO2 was used in this study as a cement replacement in refractory castable. The present study, in its first stage, offers an assessment of five different SiO2 colloidal solutions. The particle size of the solutions was 15 nm, the particle concentration was 30% and 40% and the colloidal solutions were stabilized with Na+, OH- and Cl- ions. The effect of the colloidal solutions on selected characteristics of the refractory pastes and on their mineralogical composition after firing at 1000 °C and 1500 °C was described. The most suitable SiO2 colloidal solution from the first stage was subsequently used for the refractory castable test samples' preparation in the second stage. Refractory castables, unlike paste, contain a coarse aggregate (grog) up to a grain size of 6 mm. Four types of coarse refractory grog were evaluated. Their effect on selected characteristics of the refractory castable and on its mineralogical composition after firing at 1000 °C and 1500 °C was described. The selected characteristics, within the scope of this study, include bulk density, apparent porosity, cold modulus of rupture and linear changes after firing. Finally, the study describes the effect of the sol particle concentration and the effect of pore size distribution on corrosion resistance and on the internal structure of the material. Mineral and chemical compositions and microstructures of both the raw materials and designed aggregates were thoroughly investigated by the means of X-ray fluorescence spectroscopy, powder X-ray diffraction and scanning electron microscopy. An analysis of the transition zone between corrosive media (K2CO3) and tested castables showed better corrosion resistance for a sol-gel castable than an ultra-low cement castable.

Coronary angiography and percutaneous coronary intervention in cardiac arrest patients without return of spontaneous circulation.

OBJECTIVES: This study aimed to examine coronary angiography (CAG) findings, percutaneous coronary intervention (PCI) results and outcomes in out-of-hospital cardiac arrest patients (OHCA) without return of spontaneous circulation (ROSC) on admission to hospital. METHODS: We analyzed the OHCA register and compared CAG, PCI, and outcome data in patients with and without ROSC on admission to hospital. RESULTS: Between January 2012 and December 2020, 697 OHCA patients were analyzed. Of these, 163 (23%) did not have ROSC at admission. Patients without ROSC were younger (59 vs. 61 years, p = 0.001) and had a longer resuscitation time (62 vs. 18 minutes, p < 0.001) than patients with ROSC. Significant coronary artery disease was highly prevalent in both groups (65% vs. 68%, p = 0.48). Patients without ROSC had higher rates of acute coronary occlusions (42% vs. 33%, p = 0.046), specifically affecting the left main stem (16% vs. 1%, p < 0.001). PCI was performed in 81 patients (50%) without ROSC and in 295 (55%) with ROSC (p = 0.21). The success rate was 86% in patients without ROSC and 90% in patients with ROSC (p = 0.33). Thirty-day survival was 24% in patients without ROSC and 70% in patients with ROSC. CONCLUSIONS: OHCA patients without ROSC on admission to hospital had higher acute coronary occlusion rates than patients with prehospital ROSC. PCI is feasible with a high success rate in patients without ROSC. Despite prolonged resuscitation times, meaningful survival in patients admitted without ROSC is achievable.

Nationwide screening of Fabry disease in patients with hypertrophic cardiomyopathy in Czech Republic.

AIMS: Fabry disease (FD) is a rare X-linked genetic disorder caused by α-galactosidase A (AGALA) deficiency. Whereas 'classic' variant has multisystemic manifestation, the more recently described 'later-onset' variant is characterized by predominant cardiac involvement that often mimics hypertrophic cardiomyopathy (HCM). METHODS AND RESULTS: Consecutive unrelated patients with HCM were screened for FD in 16 (out of 17) cardiac centres in the Czech Republic covering specialized cardiology care from June 2017 to December 2018. AGALA activity and globotriaosylsphingosine (lyso-Gb3 ) levels were measured in all subjects using the dry blood spot method. FD was suspected in male patients with AGALA activity <1.2 µmol/h/L and in females with either low AGALA activity or lyso-Gb3  > 3.5 ng/mL. Positive screening results were confirmed by genetic testing. We evaluated 589 patients (390 males, 66%) with HCM (mean maximal myocardial thickness 19.1 ± 4.3 mm). The average age was 58.4 ± 14.7 years. In total, 17 patients (11 males, 6 females) had a positive screening result, and subsequently, six of them (four males and two females) had a genetically confirmed pathogenic GLA mutation (total prevalence of 1.02%). Five of these patients were carrying the p.N215S mutation known to cause a typical later-onset cardiac FD. CONCLUSIONS: We confirmed the prevalence of FD repeatedly reported in previous screening programmes (approximately 1% irrespective of gender) in a non-selected HCM population in Central Europe. Our findings advocate a routine screening for FD in all adult patients with HCM phenotype including both genders. The dry blood spot method used led to identification of clearly pathogenic variants.

Fractional Flow Reserve Versus Instantaneous Wave-Free Ratio in Assessment of Lesion Hemodynamic Significance and Explanation of their Discrepancies. International, Multicenter and Prospective Trial: The FiGARO Study.

Background The FiGARO (FFR versus iFR in Assessment of Hemodynamic Lesion Significance, and an Explanation of Their Discrepancies) trial is a prospective registry searching for predictors of fractional flow reserve/instantaneous wave-free ratio (FFR/iFR) discrepancy. Methods and Results FFR/iFR were analyzed using a Verrata wire, and coronary flow reserve was analyzed using a Combomap machine (both Philips-Volcano). The risk polymorphisms for endothelial nitric oxide synthase and for heme oxygenase-1 were analyzed. In total, 1884 FFR/iFR measurements from 1564 patients were included. The FFR/iFR discrepancy occurred in 393 measurements (20.9%): FFRp (positive)/iFRn (negative) type (264 lesions, 14.0%) and FFRn/iFRp (129 lesions, 6.8%) type. Coronary flow reserve was measured in 343 lesions, correlating better with iFR (R=0.56, P<0.0001) than FFR (R=0.36, P<0.0001). The coronary flow reserve value in FFRp/iFRn lesions (2.24±0.7) was significantly higher compared with both FFRp/iFRp (1.39±0.36), and FFRn/iFRn lesions (1.8±0.64, P<0.0001). Multivariable logistic regression analysis confirmed (1) sex, age, and lesion location in the right coronary artery as predictors for FFRp/iFRn discrepancy; and (2) hemoglobin level, smoking, and renal insufficiency as predictors for FFRn/iFRp discrepancy. The FFRn/iFRp type of discrepancy was significantly more frequent in patients with both risk types of polymorphisms (endothelial nitric oxide synthaser+heme oxygenase-1r): 8 patients (24.2%) compared with FFRp/iFRn type of discrepancy: 2 patients (5.9%), P=0.03. Conclusions Predictors for FFRp/iFRn discrepancy were sex, age, and location in the right coronary artery. Predictors for FFRn/iFRp were hemoglobin level, smoking, and renal insufficiency. The risk type of polymorphism in endothelial nitric oxide synthase and heme oxygenase-1 genes was more frequently found in patients with FFRn/iFRp type of discrepancy. Registration URL: https://clinicaltrials.gov; Unique identifier: NCT03033810.

4-Year Outcomes After Left Atrial Appendage Closure Versus Nonwarfarin Oral Anticoagulation for Atrial Fibrillation.

BACKGROUND: The PRAGUE-17 (Left Atrial Appendage Closure vs Novel Anticoagulation Agents in Atrial Fibrillation) trial demonstrated that left atrial appendage closure (LAAC) was noninferior to nonwarfarin direct oral anticoagulants (DOACs) for preventing major neurological, cardiovascular, or bleeding events in patients with atrial fibrillation (AF) who were at high risk. OBJECTIVES: This study sought to assess the prespecified long-term (4-year) outcomes in PRAGUE-17. METHODS: PRAGUE-17 was a randomized noninferiority trial comparing percutaneous LAAC (Watchman or Amulet) with DOACs (95% apixaban) in patients with nonvalvular AF and with a history of cardioembolism, clinically-relevant bleeding, or both CHA2DS2-VASc ≥3 and HASBLED ≥2. The primary endpoint was a composite of cardioembolic events (stroke, transient ischemic attack, or systemic embolism), cardiovascular death, clinically relevant bleeding, or procedure-/device-related complications (LAAC group only). The primary analysis was modified intention-to-treat. RESULTS: This study randomized 402 patients with AF (201 per group, age 73.3 ± 7.0 years, 65.7% male, CHA2DS2-VASc 4.7 ±1.5, HASBLED 3.1 ± 0.9). After 3.5 years median follow-up (1,354 patient-years), LAAC was noninferior to DOACs for the primary endpoint by modified intention-to-treat (subdistribution HR [sHR]: 0.81; 95% CI: 0.56-1.18; P = 0.27; P for noninferiority = 0.006). For the components of the composite endpoint, the corresponding sHRs were 0.68 (95% CI: 0.39-1.20; P = 0.19) for cardiovascular death, 1.14 (95% CI: 0.56-2.30; P = 0.72) for all-stroke/transient ischemic attack, 0.75 (95% CI: 0.44-1.27; P = 0.28) for clinically relevant bleeding, and 0.55 (95% CI: 0.31-0.97; P = 0.039) for nonprocedural clinically relevant bleeding. The primary endpoint outcomes were similar in the per-protocol (sHR: 0.80; 95% CI: 0.54-1.18; P = 0.25) and on-treatment (sHR: 0.82; 95% CI: 0.56-1.20; P = 0.30) analyses. CONCLUSIONS: In long-term follow-up of PRAGUE-17, LAAC remains noninferior to DOACs for preventing major cardiovascular, neurological, or bleeding events. Furthermore, nonprocedural bleeding was significantly reduced with LAAC. (PRAGUE-17 [Left Atrial Appendage Closure vs Novel Anticoagulation Agents in Atrial Fibrillation]; NCT02426944).

Sublingual isosorbide dinitrate for the detection of obstruction in hypertrophic cardiomyopathy.

AIMS: Hypertrophic cardiomyopathy (HCM) is predominantly associated with left ventricular outflow tract (LVOT) obstruction. The assessment of the obstruction with a provoking test should be a routine part of HCM evaluation. The aim of the study was to determine the utility of a sublingual spray application of isosorbide dinitrate (ISDN) for detection of an obstruction. METHODS AND RESULTS: We have prospectively analysed 77 consecutive HCM patients, measuring the LVOT gradient at rest, using the sublingual spray application of ISDN (2.5 mg; after 2, 5, and 10 min), and with exercise echocardiography. An obstruction was defined as a gradient ≥ 30 mmHg. An obstruction was present in 15 patients (19%) at rest, in 42 patients (55%) after ISDN, and in 55 patients (71%) after exercise. The ISDN test had a sensitivity of 76% and the specificity of 100% relative to exercise echocardiography, while at-rest measurements had a sensitivity of 27% and a specificity of 100%. The chronological difference in the prevalence of obstructions during the ISDN test was statistically significant (P < 0.05); at ISDN plus 2 min, obstructions were seen in only 29 patients (38%, gradient 28.8 ± 25.0 mmHg), however, at ISDN plus 5 and 10 min, obstructions were found in 42 patients (55%, gradient 44.5 ± 39.6 mmHg). CONCLUSION: The ISDN test is a reliable screening method for the detection of an HCM obstruction, however, the measurement should be delayed 5-10 min after the application of ISDN. Patients with negative ISDN tests should undergo exercise echocardiography.