Effect of intra-arrest transport, extracorporeal cardiopulmonary resuscitation and immediate invasive assessment in refractory out-of-hospital cardiac arrest: a long-term follow-up of the Prague OHCA trial.

BACKGROUND: Randomized data evaluating the impact of the extracorporeal cardiopulmonary resuscitation (ECPR) approach on long-term clinical outcomes in patients with refractory out-of-hospital cardiac arrest (OHCA) are lacking. The objective of this follow-up study was to assess the long-term clinical outcomes of the ECPR-based versus CCPR approach. METHODS: The Prague OHCA trial was a single-center, randomized, open-label trial. Patients with witnessed refractory OHCA of presumed cardiac origin, without return of spontaneous circulation, were randomized during ongoing resuscitation on scene to conventional CPR (CCPR) or an ECPR-based approach (intra-arrest transport, ECPR if ROSC is not achieved prehospital and immediate invasive assessment). RESULTS: From March 2013 to October 2020, 264 patients were randomized during ongoing resuscitation on scene, and 256 patients were enrolled. Long-term follow-up was performed 5.3 (interquartile range 3.8-7.2) years after initial randomization and was completed in 255 of 256 patients (99.6%). In total, 34/123 (27.6%) patients in the ECPR-based group and 26/132 (19.7%) in the CCPR group were alive (log-rank P = 0.01). There were no significant differences between the treatment groups in the neurological outcome, survival after hospital discharge, risk of hospitalization, major cardiovascular events and quality of life. Of long-term survivors, 1/34 (2.9%) in the ECPR-based arm and 1/26 (3.8%) in the CCPR arm had poor neurological outcome (both patients had a cerebral performance category score of 3). CONCLUSIONS: Among patients with refractory OHCA, the ECPR-based approach significantly improved long-term survival. There were no differences in the neurological outcome, major cardiovascular events and quality of life between the groups, but the trial was possibly underpowered to detect a clinically relevant difference in these outcomes. Trial registration ClinicalTrials.gov Identifier: NCT01511666, Registered 19 January 2012.

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.

Catheter ablation of atrial fibrillation and atrial tachycardia in patients with pulmonary hypertension: a randomized study.

AIMS: Atrial fibrillation (AF), typical atrial flutter (AFL), and other atrial tachycardias (ATs) are common in patients with pulmonary hypertension. Frequently, several supraventricular arrhythmias are successively observed in individual patients. We investigated the hypothesis of whether more extensive radiofrequency catheter ablation of the bi-atrial arrhythmogenic substrate instead of clinical arrhythmia ablation alone results in superior clinical outcomes in patients with pulmonary arterial hypertension (PH) and supraventricular arrhythmias. METHODS AND RESULTS: Patients with combined post- and pre-capillary or isolated pre-capillary PH and supraventricular arrhythmia indicated to catheter ablation were enrolled in three centres and randomized 1:1 into two parallel treatment arms. Patients underwent either clinical arrhythmia ablation only (Limited ablation group) or clinical arrhythmia plus substrate-based ablation (Extended ablation group). The primary endpoint was arrhythmia recurrence >30 s without antiarrhythmic drugs after the 3-month blanking period. A total of 77 patients (mean age 67 ± 10 years; 41 males) were enrolled. The presumable clinical arrhythmia was AF in 38 and AT in 36 patients, including typical AFL in 23 patients. During the median follow-up period of 13 (interquartile range: 12; 19) months, the primary endpoint occurred in 15 patients (42%) vs. 17 patients (45%) in the Extended vs. Limited ablation group (hazard ratio: 0.97, 95% confidence interval: 0.49-2.0). There was no excess of procedural complications and clinical follow-up events including an all-cause death in the Extended ablation group. CONCLUSION: Extensive ablation, compared with a limited approach, was not beneficial in terms of arrhythmia recurrence in patients with AF/AT and PH. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov; NCT04053361.

Electrocardiographic findings in patients with arrhythmogenic cardiomyopathy and right bundle branch block ventricular tachycardia.

AIMS: Little is known about patients with right bundle branch block (RBBB)-ventricular tachycardia (VT) and arrhythmogenic cardiomyopathy (ACM). Our aims were: (i) to describe electrocardiogram (ECG) characteristics of sinus rhythm (SR) and VT; (ii) to correlate SR with RBBB-VT ECGs; and (iii) to compare VT ECGs with electro-anatomic mapping (EAM) data. METHODS AND RESULTS: From the European Survey on ACM, 70 patients with spontaneous RBBB-VT were included. Putative left ventricular (LV) sites of origin (SOOs) were estimated with a VT-axis-derived methodology and confirmed by EAM data when available. Overall, 49 (70%) patients met definite Task Force Criteria. Low QRS voltage predominated in lateral leads (n = 37, 55%), but QRS fragmentation was more frequent in inferior leads (n = 15, 23%). T-wave inversion (TWI) was equally frequent in inferior (n = 28, 42%) and lateral (n = 27, 40%) leads. TWI in inferior leads was associated with reduced LV ejection fraction (LVEF; 46 ± 10 vs. 53 ± 8, P = 0.02). Regarding SOOs, the inferior wall harboured 31 (46%) SOOs, followed by the lateral wall (n = 17, 25%), the anterior wall (n = 15, 22%), and the septum (n = 4, 6%). EAM data were available for 16 patients and showed good concordance with the putative SOOs. In all patients with superior-axis RBBB-VT who underwent endo-epicardial VT activation mapping, VT originated from the LV. CONCLUSIONS: In patients with ACM and RBBB-VT, RBBB-VTs originated mainly from the inferior and lateral LV walls. SR depolarization and repolarization abnormalities were frequent and associated with underlying variants.

The prevalence of left and right bundle branch block morphology ventricular tachycardia amongst patients with arrhythmogenic cardiomyopathy and sustained ventricular tachycardia: insights from the European Survey on Arrhythmogenic Cardiomyopathy.

AIMS: In arrhythmogenic cardiomyopathy (ACM), sustained ventricular tachycardia (VT) typically displays a left bundle branch block (LBBB) morphology while a right bundle branch block (RBBB) morphology is rare. The present study assesses the VT morphology in ACM patients with sustained VT and their clinical and genetic characteristics. METHODS AND RESULTS: Twenty-six centres from 11 European countries provided information on 954 ACM patients who had ≥1 episode of sustained VT spontaneously documented during patients' clinical course. Arrhythmogenic cardiomyopathy was defined according to the 2010 Task Force Criteria, and VT morphology according to the QRS pattern in V1. Overall, 882 (92.5%) patients displayed LBBB-VT alone and 72 (7.5%) RBBB-VT [alone in 42 (4.4%) or in combination with LBBB-VT in 30 (3.1%)]. Male sex prevalence was 79.3%, 88.1%, and 56.7% in the LBBB-VT, RBBB-VT, and LBBB + RBBB-VT groups, respectively (P = 0.007). First RBBB-VT occurred 5 years after the first LBBB-VT (46.5 ± 14.4 vs 41.1 ± 15.8 years, P = 0.011). An implanted cardioverter-defibrillator was more frequently implanted in the RBBB-VT (92.9%) and the LBBB + RBBB-VT groups (90%) than in the LBBB-VT group (68.1%) (P < 0.001). Mutations in PKP2 predominated in the LBBB-VT (65.2%) and the LBBB + RBBB-VT (41.7%) groups while DSP mutations predominated in the RBBB-VT group (45.5%). By multivariable analysis, female sex was associated with LBBB + RBBB-VT (P = 0.011) while DSP mutations were associated with RBBB-VT (P < 0.001). After a median follow-up of 103 (51-185) months, death occurred in 106 (11.1%) patients with no intergroup difference (P = 0.176). CONCLUSION: RBBB-VT accounts for a significant proportion of sustained VTs in ACM. Sex and type of pathogenic mutations were associated with VT type, female sex with LBBB + RBBB-VT, and DSP mutation with RBBB-VT.

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.

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.

Biomarker GDF-15 in cardiology.

GDF-15 (Growth differentiation factor 15) is a protein synthesised in some tissues including liver, kidney, heart, or lung. GDF-15 a stress-responsive cytokine. GDF-15 is emerging as a biomarker of cardiometabolic risk and disease burden. GDF-15 is linked to the incidence and prognosis of heart failure. In acute coronary syndromes GDF-15 identifies risk of complications including bleeding, reinfarction, development of heart failure or mortality. In patients with atrial fibrillation, GDF-15 is a potent marker of bleeding adverse events in anticoagulated patients and a predictor of overall mortality. Role of GDF-15 in cardiology is not definitively constituted.

Atrial fibrillation and atrial tachycardia in patients with chronic thromboembolic pulmonary hypertension treated with pulmonary endarterectomy.

Atrial fibrillation (AF) and atrial tachycardia (AT) are frequently observed in patients with chronic thromboembolic pulmonary hypertension (CTEPH) who were treated with pulmonary endarterectomy (PEA). Their prevalence and impact on prognosis of patients are not known. We analysed the prevalence of AF/AT and the clinical outcome in 197 patients with CTEPH treated with PEA (median age 62; interquartile range 53-68 years; 62% males). The prevalence of AF/AT was 29% (57 patients). Compared to patients without arrhythmia, the subjects with AF/AT were older [60 (50-67) vs. 62 (57-70) years], manifested an increased size of the left atrium [39 (35-44) vs. 45 (40-50) mm], had a reduced 6-min walking distance [411 (321-506) vs. 340 (254-460) m], and higher pulmonary artery systolic pressure after PEA [38 (30-47) vs. 45 (38-71) mmHg], all results with P-value <0.05. During the follow-up with a median 4.2 (1.6-6.3) years, 45 (23%) patients died. In a multivariate Cox regression model only the male gender [hazard ratio (HR) 2.27, 95% confidence interval (CI) 1.15-4.50], a reduced 6-min walking distance (HR 3.67, 95% CI 1.74-7.73), and an increased New York Heart Association class (HR 8.56, 95% CI 4.17-17.60) were associated with mortality (P < 0.05). The prevalence of AF/AT in patients with CTEPH treated with PEA is high. Arrhythmias are associated with reduced functional capacity but not with mortality.

The left atrial substrate plays a significant role in the development of complex atrial tachycardia in patients with precapillary pulmonary hypertension.

BACKGROUND: Atrial fibrillation (AF) and related atrial tachyarrhythmias (AT), including type I atrial flutter (AFL) are frequently observed in patients with pulmonary hypertension (PH). Their relationship to hemodynamic changes, atrial size, and ventricular function are still not fully verified. METHODS: We retrospectively studied hemodynamic data, echocardiographic findings and arrhythmia incidence in 814 patients with invasively diagnosed precapillary PH (aged 59 ± 14 years; 46% males). Patients with combined or post-capillary PH were excluded. RESULTS: AF / AT were identified in 225 (28%) of all the study population. Compared to the subgroup without arrhythmia, patients with AF / AT had elevated right atrial pressure (11 ± 5 vs. 9 ± 5 mmHg), wedge pressure (11 ± 3 vs. 10 ± 3), a more enlarged right atrium (50 ± 12 vs. 47 ± 11 mm) and an increased left atrial diameter in the parasternal long axis projection, p <  0.05 for all comparisons. In the multivariate model, the left atrial size, patient age, arterial hypertension, diabetes and type of PH were associated with AF / AT occurrence, p <  0.05. Patients with type I AFL were more frequently male (39 (80%) vs. 62 (42%)), were younger (61 ± 11 vs. 67 ± 10 years), had increased pulmonary artery mean pressure (50 ± 12 vs. 45 ± 12 mmHg), less advanced left atrial dilatation (38 ± 10 vs. 42 ± 7 mm), and a more enlarged right atrium (56 ± 12 vs. 48 ± 11) as compared to subjects with AF or other AT, p <  0.05. CONCLUSIONS: The evidence of elevated wedge pressure and the enlargement of the left atrium especially in patients with AF suggest a parallel involvement of the left atrial substrate in arrhythmia formation despite invasively confirmed evidence of purely isolated precapillary PH. Substantial differences were noticed between patients with type I AFL and the remaining patients with other arrhythmia types.

3D electroanatomical mapping is less sensitive to atrial remodeling in estimation of true left atrial volume than echocardiography.

BACKGROUND: Left atrial (LA) enlargement has been identified as a predictor of worse clinical outcome after catheter ablation for atrial fibrillation (AF). We investigated the correspondence of LA size parameters assessed by echocardiography, CT and 3D electroanatomical mapping in patients with AF treated by catheter ablation. METHODS: We analyzed echocardiographic LA volume measurements by disc summation method (LAVDISC), computed tomography (LAVCT) and 3D electroanatomical mapping (LAVCARTO) in 100 pts. (71% males; aged 63 ± 8 years; paroxysmal AF in 55% of patients). RESULTS: Mean LAVDISC was 83 ± 25 ml (median: 115; IQR: 98-140 ml), mean LAVCT was 120 ± 34 ml (median: 115; IQR: 98-140 ml) and mean LAVCARTO was 123 ± 36 ml (median: 118; IQR: 99-132 ml). Pearson's correlation coefficient between LAVDISC a LAVCT was 0.6 (p < 0.0001) and between LAVCARTO and LAVCT was 0.79 (p < 0.0001). There was a significant difference between the two correlation coefficients (p < 0.004). The absolute difference between LAVCARTO and LAVCT (3.5 (95% CI -42 - 43) ml) was significantly lower (p < 0.0001) as compared to LAVDISC and LAVCT (- 39 (95% CI -102 - 24) ml). In opposite to LAVDISC, the bias between LAV obtained by CT and CARTO did not differentiate according to presence of spherical remodeling (1.7 ± 28 vs. vs. 5.1 ± 31 ml). Only presence of sinus rhythm was significant and independent covariate of the difference between CARTO and CT-derived LAVs by multivariate regression analysis. CONCLUSIONS: Even though LA volumes evaluated by 3D-electroanatomical mapping have quite good accuracy, the precision is low. For volumes estimated by echocardiography, both precision and accuracy are low.

The effect of renal denervation in an experimental model of chronic renal insufficiency, The REmnant kidney Denervation In Pigs study (REDIP study).

BACKGROUND: Renal denervation (RDN) is a promising therapeutic method in cardiology. Its currently most investigated indication is resistant hypertension. Other potential indications are atrial fibrillation, type 2 diabetes mellitus and chronic renal insufficiency among others. Previous trials showed conflicting but promising results, but the real benefits of RDN are still under investigation. Patients with renal insufficiency and resistant hypertension are proposed to be a good target for this therapy due to excessive activation of renal sympathetic drive. However, only limited number of studies showed benefits for these patients. We hypothesize that in our experimental model of chronic kidney disease (CKD) due to ischemia with increased activity of the renin-angiotensin-aldosterone system (RAAS), renal denervation can have protective effects by slowing or blocking the progression of renal injury. METHODS: An experimental biomodel of chronic renal insufficiency induced by ischemia was developed using selective renal artery embolization (remnant kidney porcine model). 27 biomodels were assessed. Renal denervation was performed in 19 biomodels (denervated group), and the remaining were used as controls (n = 8). The extent of renal injury and reparative process between the two groups were compared and assessed using biochemical parameters and histological findings. RESULTS: Viable remnant kidney biomodels were achieved and maintained in 27 swine. There were no significant differences in biochemical parameters between the two groups at baseline. Histological assessment proved successful RDN procedure in all biomodels in the denervated group. Over the 7-week period, there were significant increases in serum urea, creatinine, and aldosterone concentration in both groups. The difference in urea and creatinine levels were not statistically significant between the two groups. However, the level of aldosterone in the denervated was significantly lower in comparison to the controls. Histological assessment of renal arteries showed that RDN tends to produce more damage to the arterial wall in comparison to vessels in subjects that only underwent RAE. In addition, the morphological damage of kidneys, which was expressed as a ratio of damaged surface (or scar) to the overall surface of kidney, also did not show significant difference between groups. CONCLUSIONS: In this study, we were not able to show significant protective effect of RDN alone on ischemic renal parenchymal damage by either laboratory or histological assessments. However, the change in aldosterone level shows some effect of renal denervation on the RAAS system. We hypothesize that a combined blockade of the RAAS and the sympathetic system could provide more protective effects against acute ischemia. This has to be further investigated in future studies.

[Arrhythmogenic left ventricular cardiomyopathy]. / Arytmogenní kardiomyopatie levé komory.

Arrhythmogenic left ventricular cardiomyopathy (ALVC) is a rare condition characterised by progressive fibrofatty replacement of the myocardium of the left ventricle in combination with arrhythmias of left ventricular origin. ALVC has been linked to autosomal dominant mutations of genes encoding desmosomal proteins, similarly to the classic arrhythmogenic right ventricular cardiomyopathy with which it also shares pathological and prognostic features. It seems that isolated left or right ventricular abnormalities represent two extremes of the spectrum of clinical manifestations of a single disease: arrhythmogenic cardiomyopathy. In addition to arrhythmias originating from the left ventricle, the diagnosis of ALVC is based on identification of morphological changes of the left ventricle including late gadolinium enhancement with subepicardial to midwall distribution, corresponding to fibrous or fibrofatty replacement on histopathology. The diagnosis is confirmed by detection of a causal mutation. ALVC should be kept in mind in the differential diagnosis of ventricular tachycardia of non-ischemic origin.Key words: arrhythmogenic cardiomyopathy - cardiac magnetic resonance - late gadolinium enhancement - ventricular tachycardia.

Inducibility of ventricular fibrillation during mild therapeutic hypothermia: electrophysiological study in a swine model.

INTRODUCTION: Mild therapeutic hypothermia (MTH) is being used after cardiac arrest for its expected improvement in neurological outcome. Safety of MTH concerning inducibility of malignant arrhythmias has not been satisfactorily demonstrated. This study compares inducibility of ventricular fibrillation (VF) before and after induction of MTH in a whole body swine model and evaluates possible interaction with changing potassium plasma levels. METHODS: The extracorporeal cooling was introduced in fully anesthetized swine (n = 6) to provide MTH. Inducibility of VF was studied by programmed ventricular stimulation three times in each animal under the following: during normothermia (NT), after reaching the core temperature of 32°C (HT) and after another 60 minutes of stable hypothermia (HT60). Inducibility of VF, effective refractory period of the ventricles (ERP), QTc interval and potassium plasma levels were measured. RESULTS: Starting at normothermia of 38.7 (IQR 38.2; 39.8)°C, HT was achieved within 54 (39; 59) minutes and the core temperature was further maintained constant. Overall, the inducibility of VF was 100% (18/18 attempts) at NT, 83% (15/18) after reaching HT (P = 0.23) and 39% (7/18) at HT60 (P = 0.0001) using the same protocol. Similarly, ERP prolonged from 140 (130; 150) ms at NT to 206 (190; 220) ms when reaching HT (P < 0.001) and remained 206 (193; 220) ms at HT60. QTc interval was inversely proportional to the core temperature and extended from 376 (362; 395) at NT to 570 (545; 599) ms at HT. Potassium plasma level changed spontaneously: decreased during cooling from 4.1 (3.9; 4.8) to 3.7 (3.4; 4.1) mmol/L at HT (P < 0.01), then began to increase and returned to baseline level at HT60 (4.6 (4.4; 5.0) mmol/L, P = NS). CONCLUSIONS: According to our swine model, MTH does not increase the risk of VF induction by ventricular pacing in healthy hearts. Moreover, when combined with normokalemia, MTH exerts an antiarrhythmic effect despite prolonged QTc interval.

Arrhythmogenic substrate at the interventricular septum as a target site for radiofrequency catheter ablation of recurrent ventricular tachycardia in left dominant arrhythmogenic cardiomyopathy.

BACKGROUND: Left dominant arrhythmogenic cardiomyopathy (LDAC) is a rare condition characterised by progressive fibrofatty replacement of the myocardium of the left ventricle (LV) in combination with ventricular arrhythmias of LV origin. CASE PRESENTATION: A thirty-five-year-old male was referred for evaluation of recurrent sustained monomorphic ventricular tachycardia (VT) of 200 bpm and right bundle branch block (RBBB) morphology. Cardiac magnetic resonance imaging showed late gadolinium enhancement distributed circumferentially in the epicardial layer of the LV free wall myocardium including the rightward portion of the interventricular septum (IVS). The clinical RBBB VT was reproduced during the EP study. Ablation at an LV septum site with absence of abnormal electrograms and a suboptimum pacemap rendered the VT of clinical morphology noninducible. Three other VTs, all of left bundle branch block (LBBB) pattern, were induced by programmed electrical stimulation. The regions corresponding to abnormal electrograms were identified and ablated at the mid-to-apical RV septum and the anteroseptal portion of the right ventricular outflow tract. No abnormalities were found at the RV free wall including the inferolateral peritricuspid annulus region. Histological examination confirmed the presence of abnormal fibrous and adipose tissue with myocyte reduction in endomyocardial samples taken from both the left and right aspects of the IVS. CONCLUSION: LDAC rarely manifests with sustained monomorphic ventricular tachycardia. In this case, several VTs of both RBBB and LBBB morphology were amenable to endocardial radiofrequency catheter ablation.

Recent-onset dilated cardiomyopathy associated with Borrelia burgdorferi infection.

BACKGROUND: Several recent small studies have suggested a causal link between Lyme disease and dilated cardiomyopathy (DCM) by demonstrating the presence of the Borrelia burgdorferi (Bb) genome in the myocardium of patients with recent-onset DCM. The aim of this study was to further investigate the effect of targeted antibiotic treatment of Bb-related recent-onset DCM in a larger cohort of patients. PATIENTS AND METHODS: We performed endomyocardial biopsy (EMB) in 110 individuals (53 ± 11 years, 34 women) with recent-onset unexplained DCM, and detected the Bb genome in 22 (20 %) subjects. Bb-positive patients were subsequently treated with intravenous ceftriaxone for 21 days in addition to conventional heart failure medication. RESULTS: At the 1-year follow-up, a significant improvement in left ventricular (LV) ejection fraction (26 ± 6 vs. 44 ± 12 %; p < 0.01) and a decrease in LV end-diastolic (69 ± 7 vs. 63 ± 11 mm; p < 0.01) and end-systolic (61 ± 9 vs. 52 ± 4 mm; p < 0.01) diameters were documented. Moreover, a significant improvement in heart failure symptoms (NYHA class 3.4 ± 0.6 vs. 1.5 ± 0.7; p < 0.01) was also observed. CONCLUSION: Targeted antibiotic treatment of Bb-related recent-onset DCM in addition to conventional heart failure therapy is associated with favorable cardiac remodeling and improvement of heart failure symptoms.

Electromuscular incapacitating devices discharge and risk of severe bradycardia.

Electromuscular incapacitating devices (EMDs) are high-voltage, low-current stimulators causing involuntary muscle contractions and sensory response. Existing evidence about cardiac effects of EMD remains inconclusive. The aim of our study was to analyze electrocardiographic, echocardiographic, and microvolt T-wave alternans (MTWA) changes induced by EMD discharge.We examined 26 volunteers (22 men; median age 30 years) who underwent single standard 5-second duration exposure to TASER X26 under continuous echocardiographic and electrocardiographic monitoring. Microvolt T-wave alternans testing was performed at baseline (MTWA-1), as well as immediately and 60 minutes after EMD exposure (MTWA-2 and MTWA-3, respectively).Mean heart rate (HR) increased significantly from 88 ± 17 beats per minute before to 129 ± 17 beats per minute after exposure (P < 0.001). However, in 2 individuals, an abrupt decrease in HR was observed. In one of them, interval between two consecutive beats increased up to 1.7 seconds during the discharge. New onset of supraventricular premature beats was observed after discharge in 1 patient. Results of MTWA-1, MTWA-2, and MTWA-3 tests were positive in one of the subjects, each time in a different case.Standard EMD exposure can be associated with a nonuniform reaction of HR and followed by heart rhythm disturbances. New MTWA positivity can reflect either the effect of EMD exposure or a potential false positivity of MTWA assessments.

The Cortisol to Cortisone Ratio during Cardiac Catheterisation in Sows.

A possible effect of mini-invasive heart intervention on a response of hypothalamo-pituitary-adrenal stress axis and conversion of cortisone to cortisol were studied. We have analysed two stress markers levels (cortisol, cortisone) and cortisol/cortisone ratio in 25 sows using minimally invasive heart catheterisation as the stress factor. The values of studied parameters were assessed in four periods of the experiment: (1) the baseline level on the day before intervention, (2) after the introduction of anaesthesia, (3) after conducting tissue stimulation or ablation, and (4) after the end of the catheterisation. For statistical analyses we used the non-parametric Friedman test for four dependent samples (including all four stages of the operation) or three dependent samples (influence of operation only, baseline level was excluded). Statistically significant differences in both Friedman tests were found for cortisol and for cortisone. We have found the highest level of cortisol/cortisone ratio in unstressed conditions, then it decreased to the minimal level at the end of the intervention. We have concluded that cortisol levels are blunted by the influence of anaesthesia after its administration, and therefore decrease back to the baseline at the end of the operation.

Benefits from catheter ablation in patients with pulmonary hypertension: Recent advances.

Supraventricular tachycardia (SVT) is a frequent complication of pulmonary hypertension (PH). The most prevalent SVTs are atrial fibrillation (AF) and typical atrial flutter (AFL), followed by focal and macroreentrant atrial tachycardia (AT) and nodal arrhythmia (AV nodal reentry tachycardia or AV reentry tachycardia). SVT is frequently associated with functional deterioration and right ventricular failure in PH patients. According to some data, reestablishing sinus rhythm is associated with clinical improvement. Catheter ablation of typical AFL, nodal tachyarrhythmias, or other less complex focal ATs have been shown to be feasible, acutely effective, and safe in patients with PH. However, the long-term clinical outcome is modified by the recurrence of index arrhythmia and the onset of a new SVT. Due to right atrial dilatation, technical issues can arise when ablation is carried out. The role of catheter ablation in patients with AF or more complex AT is even less effective. The results mirror the success rate in the general AF population with non-paroxysmal AF. However, the data is limited, and electrophysiological procedures are also more often complicated by specific adverse events in a severely frail population. Despite these limitations, catheter ablation is the treatment of choice in less complex SVT, but the indications for AF ablation must be more individualized.

Mode and Characteristics of Arrhythmia Initiation in Idiopathic Ventricular Fibrillation: A THESIS Substudy.

BACKGROUND: There is limited information on the mode of arrhythmia initiation in idiopathic ventricular fibrillation (IVF). A non-pause-dependent mechanism has been suggested to be the rule. OBJECTIVES: The aim of this study was to assess the mode and characteristics of initiation of polymorphic ventricular tachycardia (PVT) in patients with short or long-coupled PVT/IVF included in THESIS (THerapy Efficacy in Short or long-coupled idiopathic ventricular fibrillation: an International Survey), a multicenter study involving 287 IVF patients treated with drugs or radiofrequency ablation. METHODS: We reviewed the initiation of 410 episodes of ≥1 PVT triplet in 180 patients (58.3% females; age 39.6 ± 13.6 years) with IVF. The incidence of pause-dependency arrhythmia initiation (prolongation by >20 ms of the preceding cycle length) was assessed. RESULTS: Most arrhythmias (n = 295; 72%) occurred during baseline supraventricular rhythm without ambient premature ventricular complexes (PVCs), whereas 106 (25.9%) occurred during baseline rhythm including PVCs. Nine (2.2%) arrhythmias occurred during atrial/ventricular pacing and were excluded from further analysis. Mode of PVT initiation was pause-dependent in 45 (15.6%) and 64 (60.4%) of instances in the first and second settings, respectively, for a total of 109 of 401 (27.2%). More than one type of pause-dependent and/or non-pause-dependent initiation (mean: 2.6) occurred in 94.4% of patients with ≥4 events. Coupling intervals of initiating PVCs were <350 ms, 350-500 ms, and >500 ms in 76.6%, 20.72%, and 2.7% of arrhythmia initiations, respectively. CONCLUSIONS: Pause-dependent initiation occurred in more than a quarter of arrhythmic episodes in IVF patients. PVCs having long (between 350 and 500 ms) and very long (>500 ms) coupling intervals were observed at the initiation of nearly a quarter of PVT episodes.