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Abstract Background Statins have been proved to be effective in reduction of mortality and morbidity when started in the early secondary prevention in stabilized patients after acute coronary syndrome (ACS). The safety and efficacy of statin administration directly in the first-line therapy in unstable ACS patients is not clear. The aim of our study was, therefore, to assess the effect of statin treatment initiated immediately at hospital admission of patients with ACS. Methods The trial was stopped prematurely after enrollment of one hundred and fifty-six patients with ACS that were randomized at admission to fluvastatin 80 mg (N = 78) or placebo (N = 78). Study medication was administered immediately after randomization and then once daily for 30 days; all patients were then encouraged to continue in open-label statin therapy and at the end of one-year follow-up 75% in the fluvastatin group and 78% in the placebo group were on statin therapy. Results We did not demonstrate any difference between groups in the level of C-reactive protein, interleukin 6, and pregnancy-associated plasma protein A on Day 2 and Day 30 (primary endpoint). Fluvastatin-therapy, however, significantly reduced one-year occurrence of major adverse cardiovascular events (11.5% vs. 24.4%, odds ratio (OR) 0.40, 95% CI 0.17-0.95, P = 0.038). This difference was caused mainly by reduction of recurrent symptomatic ischemia (7.7% vs. 20.5%, OR 0.32, 95% CI 0.12-0.88, P = 0.037). Conclusions This study failed to prove the effect of fluvastatin given as first-line therapy of ACS on serum markers of inflammation and plaque instability. Fluvastatin therapy was, however, safe and it may reduce cardiovascular event rate that supports immediate use of a statin in patients admitted for ACS. Trial registration NCT00171275

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., (© 2023 The Authors. Catheterization and Cardiovascular Interventions published by Wiley Periodicals LLC.)

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., (© 2023 The Authors. Journal of Cardiovascular Electrophysiology published by Wiley Periodicals LLC.)

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 &lt; 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 &lt; 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., (© 2022. The Author(s).)

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.

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., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [This work was supported by a research grant from the Ministry of Health, Czech Republic – conceptual development of research organization, General University Hospital in Prague, 00064165. There is no other relevant conflict of interest.], (Copyright © 2022 Elsevier B.V. All rights reserved.)

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 synthase r +heme oxygenase-1 r ): 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.

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.

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 CHA 2 DS 2 -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, CHA 2 DS 2 -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)., Competing Interests: Funding Support and Author Disclosures This work was supported by a research grant AZV 15-29565A from the Ministry of Health, Czech Republic. Dr Osmancik has received occasional speaking honoraria from Bayer and Abbott. Dr Taborsky has served on Advisory Boards for Bayer and Pfizer. Dr Kala has served on an Advisory Board and Speakers Bureau for Bayer; has served on an Advisory Board for Boston Scientific; and has received consulting fees from Boston Scientific. Dr Poloczek has received speaking honoraria from Abbott. Dr Haman has received speaking honoraria from Pfizer. Dr Zemanek has received speaking honoraria from Abbott and Bayer. Dr Peichl has received occasional speaking honoraria from Abbott; and has received consulting fees from Abbott, Biotronik, and Medtronic. Dr Havranek has received speaking honoraria from Boehringer Ingelheim; and has served on an Advisory Board for Boehringer Ingelheim. Dr Widimsky has received occasional honoraria from Bayer, Pfizer, and Boehringer Ingelheim. Dr Reddy has received consulting income and grant support from Abbott Inc and Boston Scientific Inc; unrelated to this manuscript, he has also served as a consultant for Ablacon, Acutus Medical, Affera, Apama Medical, APN Health, Aquaheart, Atacor, Autonomix, Axon Therapies, Backbeat, BioSig, Biosense Webster, BioTel Heart, Biotronik, Cardiac Implants, CardiaCare, Cardiofocus, Cardionomic, CardioNXT/AFTx, Circa Scientific, CoreMap, Corvia Medical, Dinova-Hangzhou DiNovA EP Technology, East End Medical, EBR, EPD, Epix Therapeutics, EpiEP, Eximo, Farapulse, Fire1, Gore and Associates, HRT, Impulse Dynamics, Intershunt, Javelin, Kardium, Keystone Heart, LuxMed, Medlumics, Medtronic, Middlepeak, Nuvera, Philips, Pulse Biosciences, Sirona Medical, and Valcare Vizaramed; and owns equity in Ablacon, Acutus Medical, Affera, Apama Medical, APN Health, Aquaheart, Atacor, Autonomix, Axon Therapies, Backbeat, BioSig, Cardiac Implants, CardiaCare, CardioNXT/AFTx, Circa Scientific, Corvia Medical, Dinova-Hangzhou DiNovA EP Technology, East End Medical, EPD, Epix Therapeutics, EpiEP, Eximo, Farapulse, Fire1, HRT, Intershunt, Javelin, Kardium, Keystone Heart, LuxMed, Manual Surgical Sciences, Medlumics, Middlepeak, Newpace, Nuvera, Pulse Biosciences, Sirona Medical, Surecor, Valcare, and Vizaramed. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: EXPLORER-HCM (Clinical Study to Evaluate Mavacamten [MYK-461] in Adults With Symptomatic Obstructive Hypertrophic Cardiomyopathy) demonstrated that mavacamten, a cardiac myosin inhibitor, improves symptoms, exercise capacity, and left ventricular outflow tract (LVOT) obstruction in patients with obstructive hypertrophic cardiomyopathy (oHCM)., Objectives: The purpose of this study was to evaluate mavacamten's effect on measures of cardiac structure and function and its association with changes in other clinical measures., Methods: Key echocardiographic parameters from serial echocardiograms over 30 weeks from 251 symptomatic oHCM patients (mavacamten [n = 123], placebo [n = 128]) were assessed in a core laboratory., Results: More patients on mavacamten (80.9%; n = 76 of 94) vs placebo (34.0%; n = 33 of 97) showed complete resolution of mitral valve systolic anterior motion after 30 weeks (difference, 46.8%; P < 0.0001). Mavacamten also improved measures of diastolic function vs placebo, including left atrial volume index (LAVI) (mean ± SD baseline: 40 ± 12 mL/m 2 vs 41 ± 14 mL/m 2 ; mean change from baseline of -7.5 mL/m 2 [95% CI: -9.0 to -6.1 mL/m 2 ] vs -0.09 mL/m 2 [95% CI: -1.6 to 1.5 mL/m 2 ]; P < 0.0001) and lateral E/e' (baseline, 15 ± 6 vs 15 ± 8; change of -3.8 [95% CI: -4.7 to -2.8] vs 0.04 [95% CI: -0.9 to 1.0]; P < 0.0001). Among mavacamten-treated patients, improvement in resting, Valsalva, and post-exercise LVOT gradients, LAVI, and lateral E/e' was associated with reduction in N-terminal pro-B-type natriuretic peptide (P ≤ 0.03 for all). Reduction in LAVI was associated with improved peak exercise oxygen consumption (P = 0.04)., Conclusions: Mavacamten significantly improved measures of left ventricular diastolic function and systolic anterior motion. Improvement in LVOT obstruction, LAVI, and E/e' was associated with reduction in a biomarker of myocardial wall stress (N-terminal pro-B-type natriuretic peptide). These findings demonstrate improvement in important markers of the pathophysiology of oHCM with mavacamten. (Clinical Study to Evaluate Mavacamten [MYK-461] in Adults With Symptomatic Obstructive Hypertrophic Cardiomyopathy; NCT03470545)., Competing Interests: Funding Support and Author Disclosures Study funding was provided by MyoKardia, Inc, Brisbane, CA, a wholly owned subsidiary of Bristol Myers Squibb. Dr Hegde serves on the faculty of the Cardiovascular Imaging Core Laboratory at Brigham and Women’s Hospital; and her institution has received payments for her consulting work from MyoKardia. Dr Lester’s institution has received payments for his consulting work for MyoKardia. Dr Solomon is Director of the Cardiovascular Imaging Core Laboratory at Brigham and Women’s Hospital; has received research grants from Actelion, Alnylam, Amgen, AstraZeneca, Bellerophon, Bayer, Bristol Myers Squibb, Celladon, Cytokinetics, Eidos, Gilead, GlaxoSmithKline, Ionis, Lilly, Lone Star Heart, Mesoblast, MyoKardia, National Institutes of Health/National Heart, Lung, and Blood Institute, NeuroTronik, Novartis, Novo Nordisk, Respicardia, Sanofi Pasteur, and Theracos; and has consulted for Abbott, Action Akros, Alnylam, Amgen, Arena, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Cardior, Cardurion, Corvia, Cytokinetics, Daiichi-Sankyo, Gilead, GlaxoSmithKline, Ironwood, Lilly, Merck, MyoKardia, Novartis, Roche, Takeda, Theracos, Quantum Genetics, AOBiome, Janssen, Cardiac Dimensions, Tenaya, Sanofi Pasteur, DiNAQOR, Tremeau, CellProthera, Moderna, and American Regent. Dr Michels has received personal fees and payments as a consultant from MyoKardia. Dr Elliott has received payments as a consultant from MyoKardia, Pfizer, AstraZeneca, and Sanofi Genzyme; and has received speaker fees from Sanofi Genzyme. Dr Zemanek has received speaking honoraria from Abbott and Bayer. Dr Zwas has received personal fees from MyoKardia. Dr Jacoby has received personal fees from MyoKardia. Dr Wang has received grants and payments as a consultant from MyoKardia; and has received personal fees from Cytokinetics. Dr Ho has received payments as a consultant from MyoKardia, Tenaya, Novartis, and Ambry Genetics. Drs Li and Sehnert are employees of and have stocks or stock options in MyoKardia. Dr Olivotto has received grants from MyoKardia, Sanofi Genzyme, Shire, and Bayer; has received personal fees from Sanofi Genzyme, Shire, Amicus, and Bayer; and has received payments as a consultant from MyoKardia and Cytokinetics. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Mucopolysaccharidosis type VII (MPS VII) is a rare autosomal recessive lysosomal storage disorder. MPS VII is caused by mutations in the GUSB gene that encodes β-glucuronidase. Adult MPS VII patients present with musculoskeletal abnormalities, coarse features, and corneal clouding. Cardiac and valvular impairment are common; however, severe valvular disease necessitating surgery has not yet been reported. We present a 32-year-old male MPS VII patient admitted to our hospital with decompensated heart failure. We identified aortic valve disease with severe stenosis (valve area 0.69 cm 2 ) and moderate regurgitation. Severe mitral valve stenosis (valve area 1 cm 2 ) with moderate to severe regurgitation was also found in the patient. In addition, an occlusion of the right coronary artery (RCA) was documented. The patient underwent surgical replacement of the mitral and aortic valves with mechanical prostheses and implantation of a venous bypass graft to his RCA. The surgery led to a significant improvement of his clinical symptoms. Six months after the procedure, both mechanical valves function normally. Histopathological assessment identified chronic inflammatory infiltrates, fibrosis and calcifications in both resected valves. Foamy cytoplasmic transformation was most evident in the valvular interstitial cells. The ultrastructural vacuolar abnormality seen in these cells corresponded to storage changes observed in other MPSs. In conclusion, we describe clinical findings and valvular pathology in an MPS VII patient with the first-reported successful combined surgical valve replacement and myocardial revascularization. The histological and ultrastructural analyses revealed that the lysosomal storage predominantly affected the valvular interstitial cells., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: We tested whether the level of endothelial dysfunction assessed by digital tonometry, and expressed as reactive hyperemia index (RHI), is related to occurrences of a discrepancy between fractional flow reserve (FFR) and the instantaneous wave free ratio (iFR) (ClinicalTrials.gov identifier: NCT03033810). Methods: We examined patients with coronary stenosis in the range of 40-70%, assessed by both FFR and iFR (system Philips-Volcano) for stable angina. We included consecutive patients with FFR and iFR in one native coronary artery, and who had had no previous intervention. Results: We included 138 patients. Out of those, 24 patients (17.4%) had a negative FFR (with an FFR value >0.8) and positive iFR (with a iFR value ≤0.89) - designated the FFRn/iFRp discrepancy group, and 22 patients (15.9%) had a positive FFR (≤0.8) and negative iFR (>0.89) - designated the FFRp/iFRn discrepancy. RHI was higher in the discrepancy groups compared the group without discrepancy (1.73 ± 0.79 vs. 1.48 ± 0.50, p  = 0.025). However, this finding was not confirmed in multivariant logistic regression analyses. Patients with any type of discrepancy differed from the agreement group by having a higher occurrence of diabetes mellitus [9 patients (21.4%) vs. 36 patients (39.6%), p  = 0.029], active smoking (23 patients or 54.8% vs. 26 patients or 28.6%, p  = 0.003) and lower use of calcium channel blockers (9 patients, 21.4%, vs. 43 patients, 46.7%, p  = 0.004). Conclusion: The presence of endothelial dysfunction can be associated with a discrepancy in FFR/iFR. However, RHI correlated with risk factors of atherosclerosis, not with FFR or iFR.

Background: Percutaneous left atrial appendage closure (LAAC) is noninferior to vitamin K antagonists (VKAs) for preventing atrial fibrillation (AF)-related stroke. However, direct oral anticoagulants (DOACs) have an improved safety profile over VKAs, and their effect on cardiovascular and neurological outcomes relative to LAAC is unknown., Objectives: This study sought to compare DOACs with LAAC in high-risk patients with AF., Methods: Left Atrial Appendage Closure vs. Novel Anticoagulation Agents in Atrial Fibrillation (PRAGUE-17) was a multicenter, randomized, noninferiority trial comparing LAAC with DOACs. Patients were eligible to be enrolled if they had nonvalvular AF; were indicated for oral anticoagulation (OAC); and had a history of bleeding requiring intervention or hospitalization, a history of a cardioembolic event while taking an OAC, and/or a CHA 2 DS 2 -VASc of ≥3 and HAS-BLED of >2. Patients were randomized to receive LAAC or DOAC. The primary composite outcome was stroke, transient ischemic attack, systemic embolism, cardiovascular death, major or nonmajor clinically relevant bleeding, or procedure-/device-related complications. The primary analysis was by modified intention to treat., Results: A high-risk patient cohort (CHA 2 DS 2 -VASc: 4.7 ± 1.5) was randomized to receive LAAC (n = 201) or DOAC (n = 201). LAAC was successful in 181 of 201 (90.0%) patients. In the DOAC group, apixaban was most frequently used (192 of 201; 95.5%). At a median 19.9 months of follow-up, the annual rates of the primary outcome were 10.99% with LAAC and 13.42% with DOAC (subdistribution hazard ratio [sHR]: 0.84; 95% confidence interval [CI]: 0.53 to 1.31; p = 0.44; p = 0.004 for noninferiority). There were no differences between groups for the components of the composite endpoint: all-stroke/TIA (sHR: 1.00; 95% CI: 0.40 to 2.51), clinically significant bleeding (sHR: 0.81; 95% CI: 0.44 to 1.52), and cardiovascular death (sHR: 0.75; 95% CI: 0.34 to 1.62). Major LAAC-related complications occurred in 9 (4.5%) patients., Conclusions: Among patients at high risk for stroke and increased risk of bleeding, LAAC was noninferior to DOAC in preventing major AF-related cardiovascular, neurological, and bleeding events. (Left Atrial Appendage Closure vs. Novel Anticoagulation Agents in Atrial Fibrillation [PRAGUE-17]; NCT02426944)., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

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.

Atherosclerosis is the most common cause of both carotid and coronary steno-occlusive disease. Rupture of an atherosclerotic plaque may lead to the formation of an overlying thrombosis resulting in complete arterial occlusion or downstream embolism. Clinically, this may manifest as a stroke or acute myocardial infarction, the overall leading causes of mortality and disability in developed countries. In this article, we summarize current concepts of the development of vulnerable plaque and provide an overview of commonly used imaging methods that may suggest/indicate atherosclerotic plaque vulnerability.

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 CHA 2 DS 2 VASc ≥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., (Copyright © 2016 Elsevier Inc. All rights reserved.)

We present a case report of two rare arterial anomalies diagnosed during transradial coronary catheterization-arteria lusoria (aberrant right subclavian artery) and superdominant right coronary artery. Importantly, these anomalies may cause difficulty in performance or interpretation of catheterization procedure, especially in urgent situation and with wide acceptance of transradial approach. To the best of our knowledge, the combination of these anomalies has never been described in the literature.

Introduction: A left ventricular outflow tract (LVOT) obstruction assessment with a provoking test should be a routine part of the evaluation of patients with hypertrophic cardiomyopathy (HCM). The aim of this study was to compare the utility of the Valsalva maneuver (VM) and sublingual spray application of isosorbide dinitrate (ISDN) for detection of an obstruction., Material and Methods: We prospectively evaluated 81 consecutive HCM patients without severe rest LVOT obstruction (defined as peak rest pressure gradient (PG) ≥ 50 mm Hg). We measured PG at rest, during the VM, after sublingual ISDN spray, and during the VM after ISDN. An obstruction was defined as a PG ≥ 30 mm Hg., Results: An obstruction was present in 15 patients (19%) at rest (median and interquartile range of PG 16 (7-26) mm Hg), in 38 patients (47%) during the VM (PG 28 (12-49) mm Hg), in 50 (62%) patients after ISDN (PG 50 (12-79) mm Hg), and in 55 patients (68%) during the VM after ISDN (PG 59 (20-87) mm Hg). The difference in occurrence of obstruction among different provoking tests was statistically significant for all comparisons (p < 0.001, except for the comparison of the ISDN test with the VM during ISDN, p = 0.025)., Conclusions: The ISDN test and the VM are useful screening methods for the detection of an HCM obstruction. Although ISDN appears to be more precise than the VM, the best option is a combination of both methods, which maximizes inducement of LVOT obstruction in patients with HCM.

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., (© 2015 S. Karger AG, Basel.)

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., (© 2013 Wiley Periodicals, Inc.)

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.

Background: Alcohol septal ablation (ASA) is a catheter-based intervention that has been used as an alternative to surgical myectomy in highly symptomatic patients with hypertrophic obstructive cardiomyopathy (HOCM). However, clinically relevant complications can result, including death and complete heart block (CHB) associated with syncope or resuscitation. This study was designed to evaluate the incidence of major ASA-related adverse cardiac events., Methods: This international multicentre retrospective study included 421 patients in 8 European centres who were treated using ASA from April 1998 to January 2011. Clinical and echocardiographic follow-up (3-6 months) was completed in 394 patients (94%)., Results: ASA led to a significant reduction in symptoms and outflow gradients, with 0.7% mortality. A total of 70 patients (17%) experienced mostly transient CHB during and after the procedure; in 30% of them, CHB occurred or recurred later than 24 hours after ASA. Ninety-seven percent of CHB occurred up to the fifth day after ASA. Permanent pacemakers for CHB were implanted in 35 patients (8%). Multivariate analysis identified intraprocedural bundle branch block and age as independent predictors of CHB., Conclusions: The results of the multicentre study demonstrate that ASA appears safe and efficacious, with low early mortality. The most frequent major complication after ASA was CHB (17%), which occurred late or was recurrent in almost one-third of these patients; 8% of patients required permanent pacemaker implantation. Independent predictors of CHB development were intraprocedural bundle branch block and age. Difficulty in predicting CHB should lead to close postprocedural monitoring and hospital stays lasting at least 5 days., (Copyright © 2013 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Alcohol septal ablation has become a common method to relieve left ventricular outflow track gradient in selected patients with hypertrophic obstructive cardiomyopathy. There is only limited knowledge regarding inadvertent remote (nontarget) myocardial necrosis caused by septal collateral recruitment. Herein we describe a case of unexpected contrast medium leakage through newly opened septal collateral circulation immediately after low-dose ethanol injection suggesting that angiographic inspection of collateral recruitment is necessary in all cases of repeat ethanol injection., (Copyright © 2013 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Objectives: The aim of this study was to evaluate the diagnostic accuracy of dual-source computed tomography coronary angiography (CTCA) compared to coronary angiography (CAG) and intravascular ultrasound (IVUS) for detection and quantification of in-stent restenosis after left main (LM) coronary artery stenting., Materials and Methods: Fifty-one patients with percutaneous coronary intervention of the LM were prospectively evaluated. Thirty-four of them underwent 56 complete follow-up examinations (CTCA, CAG, and IVUS as gold standard examination) that focused on detection and quantification of restenosis., Results: Sensitivity, specificity, and positive and negative predictive values were 100%, 94%, 50%, and 100% for CAG, respectively, and 100%, 74%, 18%, and 100% for CTCA, respectively. There was a correlation between the minimal luminal areas (MLA) measured by CTCA and IVUS (r = 0.63; P<.01). A Bland-Altman analysis showed that the MLA measured by CTCA was underestimated (mean difference, 2.14 ± 2.24 mm²)., Conclusion: Dual-source CTCA has a high negative predictive value and might be considered a less invasive alternative to CAG for exclusion of LM in-stent restenosis. However, there was only a moderate correlation between the MLA measurements by IVUS and CTCA in the stented LMs. Moreover, the present results suggest a systematic underestimation of MLAs measured by CTCA. Therefore, finding of any restenosis according to CTCA should be re-evaluated by CAG or, better, by subsequent IVUS.

Cardiac metastases are rare diagnoses among cardiac disorders. This case demonstrates a unique presence of an obstruction in the left ventricular outflow tract caused by the metastasis of a renal carcinoma. Adequate diagnostic and therapeutic procedures were lifesaving in this potentially fatal diagnosis.

Hypertrophic cardiomyopathy (HCM) is an autosomal dominant disorder caused by mutations in cardiac sarcomeric proteins. Troponin I (TNNI3) and troponin T (TNNT2) are important parts of the sarcomere in heart muscle, and mutations in their genes are responsible for development of HCM. The prevalence of mutations in these two genes is low; hence, the data on clinical outcome are scarce. Yet, some of these mutations were shown to be malignant with a high incidence of sudden death. Here, we describe the disease course in three families affected with TNNI3 and one family with TNNT2 gene mutations. In TNNI3-HCM, the phenotypic manifestation ranged from clinically silent to sudden cardiac death with the worst prognosis observed in carriers of Ala157Val mutation in exon 7. In contrast, TNNT2-HCM was associated with favorable prognosis. Thus, the findings of the present study add evidence on the phenotypic presentation of this genetic disease.

Infective endocarditis (IE) is a relatively rare but serious complication of hypertrophic obstructive cardiomyopathy. Currently, antibiotic prophylaxis is not generally recommended in these patients. We report a case of infective endocarditis in a patient after alcohol septal ablation for hypertrophic obstructive cardiomyopathy with residual left ventricle outflow tract obstruction. To the best of our knowledge, this is the first case in the medical literature demonstrating this complication in the late postprocedural period following alcohol septal ablation.

Coronary artery anomalies remain a poorly understood topic in modern cardiology. The most important issue is the origin of the left coronary artery or the left anterior descending artery from the opposite aortic sinus, frequently associated with sudden cardiac death. We report our experience concerning the evaluation of these anomalies. From 15 April 1997 to 1 December 2004, we performed 13.407 coronary angiographies and found eight patients with these anomalies. In seven patients the coronary angiography was sufficient for the ultimate decision. However, in one case was the angiographic signs contradictory and the optimal imaging of the coronary tree was received by the multi-slice spiral computer tomography. We consider the coronary angiography a sufficient method of evaluation in most of the patients with the coronary artery anomalies, but the 'gold standard' is 3-dimensional examination by the multi-slice computer tomography or the magnetic resonance. The computer tomography is the method of the choice to distinguish interarterial, intraseptal and prepulmonary course of the left coronary artery originating from the right aortic sinus.