Cardiogenic shock (CS) is a devastating and fatal complication of acute myocardial infarction (AMI). CS can affect the pharmacokinetics and pharmacodynamics of medications. The unique properties of cangrelor make it the optimal P2Y12 inhibitor for CS-AMI, in terms of both efficacy and safety. The DAPT-SHOCK-AMI trial (ClinicalTrials.gov: NCT03551964; EudraCT: 2018-002161-19) will assess the benefits of cangrelor in patients with an initial CS-AMI undergoing primary angioplasty. This randomised, multicentre, placebo-controlled trial of approximately 550 patients (with an allowed 10% increase) in 5 countries using a double-blind design will compare initial P2Y12 inhibitor treatment strategies in patients with CS-AMI of (A) intravenous cangrelor and (B) ticagrelor administered as crushed tablets at a loading dose of 180 mg. The primary clinical endpoint is a composite of all-cause death, myocardial infarction (MI), or stroke within 30 days. The main secondary endpoints are (1) the net clinical endpoint, defined as death, MI, urgent revascularisation of the infarct-related artery, stroke, or major bleeding as defined by the Bleeding Academic Research Consortium criteria; (2) cardiovascular-related death, MI, urgent revascularisation, or heart failure; (3) heart failure; and (4) cardiovascular-related death, all (1-4) within 1 year after study enrolment. A platelet reactivity study that tests the laboratory antiplatelet benefits of cangrelor, when given in addition to standard antiplatelet therapy, will be conducted using vasodilator-stimulated phosphoprotein phosphorylation. The primary laboratory endpoints are the periprocedural rate of onset and the proportion of patients who achieve effective P2Y12 inhibition. The DAPT-SHOCK-AMI study is the first randomised trial to evaluate the benefits of cangrelor in patients with CS-AMI.

• MeSH
• adenosinmonofosfát * analogy a deriváty   terapeutické užití   škodlivé účinky   aplikace a dávkování   MeSH
• dvojitá slepá metoda MeSH
• fosfoproteiny MeSH
• infarkt myokardu * komplikace   MeSH
• inhibitory agregace trombocytů * škodlivé účinky   terapeutické užití   aplikace a dávkování   MeSH
• kardiogenní šok * mortalita   MeSH
• koronární angioplastika škodlivé účinky   MeSH
• lidé středního věku MeSH
• lidé MeSH
• multicentrické studie jako téma MeSH
• purinergní receptory P2Y - antagonisté aplikace a dávkování   škodlivé účinky   terapeutické užití   MeSH
• randomizované kontrolované studie jako téma MeSH
• senioři MeSH
• ticagrelor * terapeutické užití   aplikace a dávkování   škodlivé účinky   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• protokol klinické studie MeSH

BACKGROUND/AIM: The study aims to describe the role of diabetes in patients with heart failure. METHODS: In all, 1052 chronic heart failure patients were included in the FARmacology and NeuroHumoral Activation (FAR NHL) multicenter prospective registry. They had ejection fraction below 50% and were on stable medication for at least 1 month. RESULTS: More than one-third (38.9%) of the patients had diabetes mellitus (DM). Diabetic patients (N = 409) were older (median 67 vs. 64, p < 0.001), had higher body mass index (BMI) (30 vs. 28 kg/m2, p < 0.001), much more frequently had ischemic heart disease (71 vs. 47%, p < 0.001), hypertension (80 vs. 67%, p < 0.001), dyslipidemia (89 vs. 69%, p < 0.001), worse renal function (estimated glomerular filtration rate [eGFR] median 63 vs. 73 mL/min/1.73 m2, p < 0.001), and higher N-terminal pro-brain natriuretic peptide (NT-proBNP) (median 681 vs. 463 pg/mL, p = 0.003). All-cause death, left ventricle assist device implantation, and orthotopic heart transplantation were set as the combined primary end point, which was present in 15.5% (163 patients) within the 2-year follow-up. In the 2-year follow-up, 81.0% of patients with diabetes survived without a primary end point, while 85.4% of the patients without diabetes survived, the difference being on the verge of statistical significance (p = 0.089). DM is a statistically significant predictor of NT-proBNP value in univariate analysis, but it is not an independent predictor in a multivariate analysis. When the NT-proBNP level was high, the presence of DM did not influence the prognosis. CONCLUSION: The combination of diabetes and NT-proBNP levels may better stratify the prognosis of patients with chronic heart failure.

• MeSH
• chronická nemoc MeSH
• diabetes mellitus * krev   patofyziologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• natriuretický peptid typu B * krev   MeSH
• peptidové fragmenty krev   MeSH
• prognóza MeSH
• prospektivní studie MeSH
• registrace * MeSH
• senioři MeSH
• srdeční selhání * krev   patofyziologie   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH

Pulmonary hypertension is a group of diseases characterized by elevated pulmonary artery pressure and pulmonary vascular resistance with significant morbidity and mortality. The most prevalent type is pulmonary hypertension secondary to left heart disease (PH-LHD). The available experimental models of PH-LHD use partial pulmonary clamping by technically nontrivial open-chest surgery with lengthy recovery. We present a simple model in which the reduction of the cross-sectional area of the ascending aorta is achieved not by external clamping but by partial intravascular obstruction without opening the chest. In anesthetized rats, a blind polyethylene tubing was advanced from the right carotid artery to just above the aortic valve. The procedure is quick and easy to learn. Three weeks after the procedure, left heart pressure overload was confirmed by measuring left ventricular end-diastolic pressure by puncture (1.3 ± 0.2 vs. 0.4 ± 0.3 mmHg in controls, mean ± SD, P < 0.0001). The presence of pulmonary hypertension was documented by measuring pulmonary artery pressure by catheterization (22.3 ± 2.3 vs. 16.9 ± 2.7 mmHg, P = 0.0282) and by detecting right ventricular hypertrophy and increased muscularization of peripheral pulmonary vessels. Contributions of a precapillary vascular segment and vasoconstriction to the increased pulmonary vascular resistance were demonstrated, respectively, by arterial occlusion technique and by normalization of resistance by a vasodilator, sodium nitroprusside, in isolated lungs. These changes were comparable, but not additive, to those induced by an established pulmonary hypertension model, chronic hypoxic exposure. Intravascular partial aortic obstruction offers an easy model of pulmonary hypertension induced by left heart disease that has a vasoconstrictor and precapillary component.NEW & NOTEWORTHY We present a new, simple model of a clinically important type of pulmonary hypertension, that induced by left heart failure. Left ventricular pressure overload is induced in rats by inserting a blinded cannula into the ascending aorta via carotid artery access. This partial intravascular aortic obstruction, which does not require opening of the chest and prolonged recovery, causes pulmonary hypertension, which has a precapillary and vasoconstrictor as well as a vascular remodeling component.

• MeSH
• aorta * patofyziologie   patologie   MeSH
• arteria pulmonalis patofyziologie   patologie   MeSH
• cévní rezistence MeSH
• hypertrofie pravé komory srdeční patofyziologie   etiologie   MeSH
• krysa rodu rattus MeSH
• modely nemocí na zvířatech * MeSH
• plicní hypertenze * patofyziologie   etiologie   MeSH
• potkani Sprague-Dawley MeSH
• potkani Wistar MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

AIMS: Wearable cardioverter-defibrillators (WCDs) are indicated in patients at risk of sudden cardiac arrest who are not immediate candidates for implantable defibrillator therapy. Limitations of existing WCDs include poor compliance and high false alarm rates. The Jewel is a novel patch-WCD (P-WCD) that addresses these limitations with an adhesive-based design for near-continuous wear and a machine learning algorithm designed to minimize inappropriate detections. This was a first-in-human study of the Jewel P-WCD conducted in an electrophysiology (EP) lab to determine the safety and effectiveness of the device in terminating ventricular tachycardia/ventricular fibrillation (VT/VF) with a single shock. The aim was to evaluate the safety and effectiveness of terminating VT/VF with a single shock using the Jewel P-WCD. METHODS AND RESULTS: This was a first-in-human, prospective, single-arm, single-centre study in patients scheduled for an EP procedure in which VT/VF was expected to either spontaneously occur or be induced. The Jewel P-WCD was placed on consented patients; upon confirmation of VT/VF, a single shock (150 J) was delivered via the device. A group sequential design and Pocock alpha spending function was used to measure the observed proportion of successful VT/VF single-shock terminations. The endpoint was achieved if the lower confidence limit exceeded the performance goal of 62%, using a one-sided lower 97.4% exact confidence bound. Of 18 eligible subjects, 16 (88.9%, 97.4% confidence bound: 65.4%) were successfully defibrillated with a single shock, exceeding the primary endpoint performance goal with no adverse events. CONCLUSION: This first-in-human evaluation of the Jewel P-WCD demonstrated the safety and effectiveness of terminating VT/VF. CLINICAL TRIAL REGISTRATION: URL: https://clinicaltrials.gov/; Unique identifier: NCT05490459.

• MeSH
• defibrilátory * MeSH
• design vybavení MeSH
• dospělí MeSH
• elektrická defibrilace * přístrojové vybavení   škodlivé účinky   MeSH
• fibrilace komor * terapie   diagnóza   MeSH
• komorová tachykardie * terapie   diagnóza   patofyziologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• náhlá srdeční smrt prevence a kontrola   MeSH
• nositelná elektronika * MeSH
• prospektivní studie MeSH
• senioři MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: We previously presented the safety and early efficacy of the inspIRE study (Study for Treatment of Paroxysmal Atrial Fibrillation [PAF] by Pulsed-field Ablation [PFA] System With Irreversible Electroporation [IRE]). With the study's conclusion, we report the outcomes of the full pivotal study cohort, with an additional analysis of predictors of success. METHODS: InspIRE was a prospective, multicenter, single-arm clinical trial of drug-refractory paroxysmal atrial fibrillation. Pulmonary vein isolation was performed with a variable-loop circular catheter integrated with a 3-dimensional mapping system. Follow-up with 24-hour Holter was at 3, 6, and 12 months, as well as remote rhythm monitoring: weekly from 3 to 5 months, monthly from 6 to 12 months, and for symptoms. The primary effectiveness end point (PEE) was acute pulmonary vein isolation plus freedom from any atrial arrhythmia at 12 months. Additional subanalyses report predictors of PEE success. RESULTS: The patient cohort included 186 patients: aged 59±10 years, female 30%, and CHA2DS2-VASc 1.3±1.2. The previously reported primary adverse event rate was 0%. One serious procedure-related adverse event, urinary retention, was reported. The PEE was achieved in 75.6% (95% CI, 69.5%-81.8%). The clinical success of freedom from symptomatic recurrence was 81.7% (95% CI, 76.1%-87.2%). Simulating a monitoring method used in standard real-world practice (without protocol-driven remote rhythm monitoring), this translates to a freedom from all and symptomatic recurrence of 85.8% (95% CI, 80.8%-90.9%) or 94.0% (95% CI, 90.6%-97.5%), respectively. Multivariate analyses revealed that left ventricular ejection fraction ≥60% (adjusted odds ratio, 0.30) and patients receiving ≥48 PFA applications (adjusted odds ratio, 0.28) were independent predictors of PEE success. Moreover, PEE success was 79.2% in patients who received ≥12 PFA applications per vein compared with 57.1% in patients receiving fewer PFA applications. CONCLUSIONS: The inspIRE study confirms the safety and effectiveness of pulmonary vein isolation using the novel 3-dimensional mapping integrated circular loop catheter. An optimal number of PFA applications (≥48 total or ≥12 per vein) resulted in an improved 1-year success rate of ≈80%. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04524364.

• MeSH
• akční potenciály MeSH
• časové faktory MeSH
• design vybavení MeSH
• elektrofyziologické techniky kardiologické MeSH
• elektrokardiografie ambulantní přístrojové vybavení   MeSH
• fibrilace síní * chirurgie   patofyziologie   diagnóza   MeSH
• katetrizační ablace * přístrojové vybavení   metody   škodlivé účinky   MeSH
• lidé středního věku MeSH
• lidé MeSH
• prediktivní hodnota testů MeSH
• prospektivní studie MeSH
• recidiva MeSH
• rizikové faktory MeSH
• senioři MeSH
• srdeční frekvence MeSH
• srdeční katétry MeSH
• venae pulmonales * chirurgie   patofyziologie   MeSH
• výsledek terapie MeSH
• zobrazování trojrozměrné MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky MeSH
• multicentrická studie MeSH

• MeSH
• hemolýza * MeSH
• katetrizační ablace * škodlivé účinky   MeSH
• lidé MeSH
• srdeční katétry MeSH
• výsledek terapie MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• dopisy MeSH

AIMS: The ultra-low-temperature cryoablation (ULTC) ablation system using -196°C N2 cryogen has been reported to create lesions with freeze duration-dependent depth titratable to over 10 mm with minimum attenuation by scar. Cryocure-VT (NCT04893317) was a first-in-human clinical trial evaluating the safety and efficacy of a novel, purpose-built ULTC catheter in endocardial ablation of scar-dependent ventricular tachycardias (VTs). METHODS AND RESULTS: This prospective, multi-centre study enrolled patients referred for de novo or second ablations of recurrent monomorphic VT of both ischaemic and non-ischaemic aetiologies. Primary safety and efficacy endpoints of the study were freedom from device- or procedure-related major adverse events (MAEs) up to 30 days post-ablation, acute non-inducibility of clinical VTs at the end of the procedure, and freedom from sustained VT or implantable defibrillator intervention at 6 months. Ultra-low-temperature cryoablation was performed in 64 patients (age 67 ± 11 years, 78% ischaemic, ejection fraction = 35 ± 10%) at 9 centres. The primary acute effectiveness endpoint was achieved in 94% (51/54) of patients in whom post-ablation induction was attempted. There were no protocol-defined MAEs; four procedure-related serious adverse events resolved without clinical sequelae. At 6-month follow-up, 38 patients (60.3%) remained VT-free, and freedom from defibrillator shock was 81.0%, with no significant difference between ischaemic and non-ischaemic cohorts. In 47 patients with defibrillator for at least 6 months prior to the ablation, the VT burden was reduced from median of 4, inter-quartile range (IQR, 1-9) to 0, IQR (0-2). CONCLUSION: In this first-in-human multi-centre experience, endocardial ULTC ablation of monomorphic VT appears safe and effective in patients with both ischaemic-cardiomyopathy and non-ischaemic-cardiomyopathy. CLINICAL TRIAL REGISTRATION: NCT04893317.

• MeSH
• jizva komplikace   MeSH
• kardiomyopatie * komplikace   diagnóza   chirurgie   MeSH
• katetrizační ablace * škodlivé účinky   MeSH
• komorová tachykardie * diagnóza   etiologie   chirurgie   MeSH
• kryochirurgie * škodlivé účinky   MeSH
• lidé středního věku MeSH
• lidé MeSH
• prospektivní studie MeSH
• senioři MeSH
• teplota MeSH
• výsledek terapie MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky MeSH
• multicentrická studie MeSH

BACKGROUND: Lipid-rich plaque covered by a thin fibrous cap (FC) has been identified as a frequent morphological substrate for the development of acute coronary syndrome. Optical coherence tomography (OCT) permits the identification and measurement of the FC. Near-infrared spectroscopy (NIRS) has been approved for detection of coronary lipids. AIMS: We aimed to assess the ability of detailed OCT analysis to identify coronary lipids, using NIRS as the reference method. METHODS: In total, 40 patients with acute coronary syndrome underwent imaging of a non-culprit lesion by both NIRS and OCT. For each segment, the NIRS-derived 4 mm segment with maximal lipid core burden index (maxLCBI4mm) was assessed. OCT analysis was performed using a semi-automated method including measurement of the fibrous cap thickness (FCT) of all detected fibroatheromas. Subsequent quantitative volumetric evaluation furnished FCT, FC surface area (FC SA), lipid arc, and FC (fibrous cap) volume data. OCT features of lipid plaques were compared with maxLCBI4mm. Predictors of maxLCBI4mm >400 was assessed by using univariable and multivariable analysis. RESULTS: OCT features (mean FCT, total FC SA, FC volume, maximal, mean, and total lipid arcs) strongly correlated with the maxLCBI4mm (p = 0.012 for the mean FCT, respectively p < 0.001 for all other aforementioned features). The strongest predictors of maxLCBI4mm >400 were the maximal (p = 0.002) and mean (p = 0.002) lipid arc, and total FC SA (p = 0.012). CONCLUSIONS: We found a strong correlation between the OCT-derived features and NIRS findings. Detailed OCT analysis may be reliably used for detection of the presence of coronary lipids.

• MeSH
• akutní koronární syndrom * diagnostické zobrazování   MeSH
• aterosklerotický plát * diagnostické zobrazování   MeSH
• blízká infračervená spektroskopie metody   MeSH
• intervenční ultrasonografie metody   MeSH
• koronární cévy diagnostické zobrazování   patologie   MeSH
• lidé MeSH
• lipidy MeSH
• nemoci koronárních tepen * diagnóza   MeSH
• optická koherentní tomografie metody   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is increasingly being used for circulatory support in patients with cardiogenic shock, although the evidence supporting its use in this context remains insufficient. The ECMO-CS trial (Extracorporeal Membrane Oxygenation in the Therapy of Cardiogenic Shock) aimed to compare immediate implementation of VA-ECMO versus an initially conservative therapy (allowing downstream use of VA-ECMO) in patients with rapidly deteriorating or severe cardiogenic shock. METHODS: This multicenter, randomized, investigator-initiated, academic clinical trial included patients with either rapidly deteriorating or severe cardiogenic shock. Patients were randomly assigned to immediate VA-ECMO or no immediate VA-ECMO. Other diagnostic and therapeutic procedures were performed as per current standards of care. In the early conservative group, VA-ECMO could be used downstream in case of worsening hemodynamic status. The primary end point was the composite of death from any cause, resuscitated circulatory arrest, and implementation of another mechanical circulatory support device at 30 days. RESULTS: A total of 122 patients were randomized; after excluding 5 patients because of the absence of informed consent, 117 subjects were included in the analysis, of whom 58 were randomized to immediate VA-ECMO and 59 to no immediate VA-ECMO. The composite primary end point occurred in 37 (63.8%) and 42 (71.2%) patients in the immediate VA-ECMO and the no early VA-ECMO groups, respectively (hazard ratio, 0.72 [95% CI, 0.46-1.12]; P=0.21). VA-ECMO was used in 23 (39%) of no early VA-ECMO patients. The 30-day incidence of resuscitated cardiac arrest (10.3.% versus 13.6%; risk difference, -3.2 [95% CI, -15.0 to 8.5]), all-cause mortality (50.0% versus 47.5%; risk difference, 2.5 [95% CI, -15.6 to 20.7]), serious adverse events (60.3% versus 61.0%; risk difference, -0.7 [95% CI, -18.4 to 17.0]), sepsis, pneumonia, stroke, leg ischemia, and bleeding was not statistically different between the immediate VA-ECMO and the no immediate VA-ECMO groups. CONCLUSIONS: Immediate implementation of VA-ECMO in patients with rapidly deteriorating or severe cardiogenic shock did not improve clinical outcomes compared with an early conservative strategy that permitted downstream use of VA-ECMO in case of worsening hemodynamic status. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02301819.

• MeSH
• hemodynamika MeSH
• kardiogenní šok diagnóza   terapie   MeSH
• lidé MeSH
• mimotělní membránová oxygenace * metody   MeSH
• mortalita v nemocnicích MeSH
• retrospektivní studie MeSH
• srdeční zástava * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH

BACKGROUND: The subcutaneous implantable cardioverter-defibrillator (S-ICD) has demonstrated safety and efficacy for the treatment of malignant ventricular arrhythmias. However, a limitation of the S-ICD lies in the inability to either pace-terminate ventricular tachycardia or provide prolonged bradycardia pacing support. OBJECTIVE: The rationale and design of a prospective, single-arm, multinational trial of an intercommunicative leadless pacing system integrated with the S-ICD will be presented. METHODS: A technical description of the modular cardiac rhythm management (mCRM) system (EMPOWER leadless pacemaker and EMBLEM S-ICD) and the implantation procedure is provided. MODULAR ATP (Effectiveness of the EMPOWERTM Modular Pacing System and EMBLEMTM Subcutaneous ICD to Communicate Antitachycardia Pacing) is a multicenter, international trial enrolling up to 300 patients at risk of sudden cardiac death at up to 60 centers trial design. The safety endpoint of freedom from major complications related to the mCRM system or implantation procedure at 6 months and 2 years are significantly higher than 86% and 81%, respectively, and all-cause survival is significantly >85% at 2 years. RESULTS: Efficacy endpoints are that at 6 months mCRM communication success is significantly higher than 88% and the percentage of subjects with low and stable thresholds is significantly higher than 80%. Substudies to evaluate rate-responsive features and performance of the pacing module are also described. CONCLUSION: The MODULAR ATP global clinical trial will prospectively test the safety and efficacy of the first intercommunicating leadless pacing system with the S-ICD. This trial will allow for robust validation of device-device communication, pacing performance, rate responsiveness, and system safety.

• Publikační typ
• časopisecké články MeSH