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.

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.

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.

Screening of Fabry disease in patients with an implanted permanent pacemaker.

BACKGROUND: Anderson-Fabry disease (AFD) is an X-linked inherited lysosomal disease caused by a defect in the gene encoding lysosomal enzyme α-galactosidase A (GLA). Atrio-ventricular (AV) nodal conduction defects and sinus node dysfunction are common complications of the disease. It is not fully elucidated how frequently AFD is responsible for acquired AV block or sinus node dysfunction and if some AFD patients could manifest primarily with spontaneous bradycardia in general population. The purpose of study was to evaluate the prevalence of AFD in male patients with implanted permanent pacemaker (PM). METHODS: The prospective multicentric screening in consecutive male patients between 35 and 65 years with implanted PM for acquired third- or second- degree type 2 AV block or symptomatic second- degree type 1 AV block or sinus node dysfunction was performed. RESULTS: A total of 484 patients (mean age 54 ± 12 years at time of PM implantation) were enrolled to the screening in 12 local sites in Czech Republic. Out of all patients, negative result was found in 481 (99%) subjects. In 3 cases, a GLA variant was found, classified as benign: p.Asp313Tyr, p.D313Y). Pathogenic GLA variants (classical or non-classical form) or variants of unclear significance were not detected. CONCLUSION: The prevalence of pathogenic variants causing AFD in a general population sample with implanted permanent PM for AV conduction defects or sinus node dysfunction seems to be low. Our findings do not advocate a routine screening for AFD in all adult males with clinically significant bradycardia.

Role of magnetic resonance in the detection of cardiac involvement in patients with newly diagnosed extracardiac sarcoidosis: Single center experience.

BACKGROUND: Sarcoidosis is a systemic inflammatory disease of unknown etiology, which can affect almost any organ. Cardiac involvement determines the prognosis of the affected individuals. Its prevalence in patients with extracardiac sarcoidosis with the absence of cardiac symptoms remains unclear. Cardiac magnetic resonance (CMR) provides excellent diagnostic accuracy in the detection of heart involvement by sarcoidosis. AIM: We sought to determine the prevalence of cardiac sarcoidosis in asymptomatic individuals with newly diagnosed extracardiac sarcoidosis using CMR. METHODS: We prospectively evaluated 55 consecutive patients including 23 women with newly diagnosed extracardiac sarcoidosis who underwent contrast-enhanced CMR and had no symptoms of heart disease. The mean (standard deviation) age of patients was 43 (11) years. The presence of myocardial late gadolinium enhancement (LGE) of non-ischemic etiology on CMR examination was considered diagnostic for cardiac sarcoidosis. RESULTS: In 3 (6%) patients, the LGE pattern consistent with cardiac sarcoidosis was detected. In all patients, preserved left ventricular systolic regional and global function was present, and in none of them, the elevation of blood biomarkers of myocardial injury or overload was found. CONCLUSIONS: Our study suggests that the prevalence of cardiac involvement in patients with newly diagnosed extracardiac sarcoidosis and no symptoms of heart disease is very low as assessed by CMR. However, CMR may be considered as part of routine evaluation of patients with extracardiac sarcoidosis due to its higher diagnostic yield in comparison with echocardiography and electrocardiography, respectively.

Initial rhythm and survival in refractory out-of-hospital cardiac arrest. Post-hoc analysis of the Prague OHCA randomized trial.

BACKGROUND: The prognosis of refractory out-of-hospital cardiac arrest (OHCA) is generally poor. A recent Prague OHCA study has demonstrated that an invasive approach (including extracorporeal cardiopulmonary resuscitation, ECPR) is a feasible and effective treatment strategy in refractory OHCA. Here we present a post-hoc analysis of the role of initial rhythm on patient outcomes. METHODS: The study enrolled patients who had a witnessed OHCA of presumed cardiac cause without early recovery of spontaneous circulation. The initial rhythm was classified as either a shockable or a non-shockable rhythm. The primary outcome was a composite of 180 day-survival with Cerebral Performance in Category 1 or 2. RESULTS: 256 (median age 58y, 17% females) patients were enrolled. The median (IQR) duration of resuscitation was 52 (33-68) minutes. 156 (61%) and 100 (39%) of patients manifested a shockable and non-shockable rhythm, respectively. The primary outcome was achieved in 63 (40%) patients with a shockable rhythm and in 5 (5%) patients with a non-shockable rhythm (p < 0.001). When patients were analyzed separately based on whether the treatment was invasive (n = 124) or standard (n = 132), the difference in the primary endpoint between shockable and non-shockable initial rhythms remained significant (35/72 (49%) vs 4/52 (8%) in the invasive arm and 28/84 (33%) vs 1/48 (2%) in the standard arm; p < 0.001). CONCLUSION: An initial shockable rhythm and treatment with an invasive approach is associated with a reasonable neurologically favorable survival for 180 days despite refractory OHCA. Non-shockable initial rhythms bear a poor prognosis in refractory OHCA even when ECPR is readily available.

The prevalence and clinical outcome of supraventricular tachycardia in different etiologies of pulmonary hypertension.

PURPOSE: Patients with pulmonary hypertension (PH) frequently suffer from supraventricular tachycardias (SVT). The main purpose of our study was to identify the cumulative incidence of SVT in patients with different etiologies of PH. The secondary objective was to analyse the clinical impact of SVT. METHODS: We retrospectively studied the prevalence of SVT and the clinical outcome in 755 patients (41% males; 60 ± 15 years; mean follow-up 3.8 ± 2.8 years) with PH of different etiologies. The prevalence of SVT was analysed separately in isolated pre-capillary PH (Ipc-PH) and in patients with combined post- and pre-capillary PH (Cpc-PH). RESULTS: The prevalence of SVT in the Ipc-PH group (n = 641) was 25% (n = 162). The most prevalent arrhythmias were atrial fibrillation followed by a typical atrial flutter (17% and 4.4% of all Icp-PH patients). An excessive prevalence of SVT was found in patients with pulmonary arterial hypertension associated with congenital heart disease (35%, p = 0.01). Out of the overall study population, Cpc-PH was present in 114 (15%) patients. Patients with Cpc-PH manifested a higher prevalence of SVT than subjects with Ipc-PH (58; 51% vs. 162; 25%; p <0.0001) and were more likely to have persistent or permanent atrial fibrillation (38; 29% vs. 61; 10%; p <0.0001). Parameters significantly associated with mortality in a multivariate analysis included age, male gender, functional exercise capacity and right atrial diameter (p < 0.05). Neither diagnosis of SVT nor type of arrhythmia predicted mortality. CONCLUSIONS: The study detected a significant prevalence of SVT in the population of PH of different origins. Different spectrum and prevalence of arrhythmia might be expected in different etiologies of PH. Patients with an elevated post-capillary pressure showed a higher arrhythmia prevalence, predominantly due to an excessive number of atrial fibrillations. The diagnosis of SVT was not associated with mortality.

Early and Delayed Alteration of Atrial Electrograms Around Single Radiofrequency Ablation Lesion.

Purpose: The acute effect of radiofrequency (RF) ablation includes local necrosis and oedema. We investigated the spatiotemporal change of atrial electrograms in the area surrounding the site of single standardized pulse of RF energy. Methods: The study enrolled 12 patients (45-67 years, 10 males) with paroxysmal atrial fibrillation (AF) undergoing ablation procedure with irrigated-tip ablation catheter and 3D navigation. The high-density mapping/remapping (129 ± 63 points) within the circular area with radius of ~10 mm, centered at the pre-specified posterior left pulmonary vein antrum ablation site was performed at baseline, immediately after single RF energy delivery (25 W, 30 s, 20 ml/min) and after 30 min waiting period. Bipolar voltages of atrial electrograms (A-EGM-biV) were averaged within the central and 12 adjacent left atrium segments and their relative change was studied. Results: After the ablation, overall A-EGM-biV within the mapping zone (3.51 ± 1.89 mV at baseline) reduced to 2.83 ± 1.77 mV (immediately) and to 2.68 ± 1.58 mV (after 30 min waiting period). In per-segment pair-wise comparison, we observed highly significant change in A-EGM-biV that extended up to the distance of 8.8 mm from the lesion core. The maximum early A-EGM-biV attenuation by 39-49% (P < 0.001) was registered in segments adjacent to pulmonary vein ostia. The subsequent (delayed) A-EGM-biV reduction by 17-24% (P < 0.05) was observed in opposite direction from the lesion center. Conclusions: Significant alteration of atrial electrograms was detectable rather distant from the central lesion. Spatiotemporal development of ablation lesion was eccentric/asymmetric. While acute A-EGM-biV reduction can be attributed predominantly to direct thermal injury, delayed effects are probably due to oedema progression.

The predictive value of cardiac morphology for long-term outcome of patients undergoing catheter ablation for atrial fibrillation.

OBJECTIVE: Catheter ablation (CA) is an established therapy for selected patients with atrial fibrillation (AF), but predictors of CA ablation outcome are still not fully elucidated. The aim of the study was to identify structural and morphological parameters from computed tomography (CT) as predictors of successful CA of AF in a single center prospective cohort. METHODS: An analysis of CT scans dedicated to LA evaluation was performed in 99 patients (63 ±â€¯8 years old, 70% males, 59% paroxysmal AF) scheduled for CA of AF. Survival free of atrial fibrillation/flutter/tachycardia at 1- and 3-years was assessed. RESULTS: In overall study population, both 1- and 3-year responders had smaller distance to the first division in left superior pulmonary vein (16.3 ±â€¯5.42 mm vs. 19.1 ±â€¯7.0 mm and 14.9 ±â€¯3.6 mm vs. 18.7 ±â€¯7.0 mm; p < 0.05). One-year responders had larger ostium area of left inferior pulmonary vein (median 236 mm2 [IQR = 97] vs. 222 mm2 [IQR = 71]; p = 0.03) and less acute angle between the interatrial septum and the right superior pulmonary vein (102 ±â€¯20° vs. 95 ±â€¯10°; p = 0.03). Three-years' responders had smaller ostium area of the right superior pulmonary vein (248 ±â€¯94 mm2 vs. 364 ±â€¯282 mm2; p = 0.02). Multivariate Cox regression analysis identified different predictors in paroxysmal and non-paroxysmal AF. For patients with paroxysmal AF, the predictors were angle to right superior pulmonary vein and left superior/inferior pulmonary veins carina thickness with hazard ratios of 0.965 (95%CI 0.939 to 0.992, p = 0.010) and 0.747 (95%CI 0.591 to 0.944, p = 0.015). In patients with persistent AF, the predictors were gender and NYHA stage with hazard ratios of 4.9 (95%CI 1.758 to 13.579, p = 0.002) and 0.365 (95%CI 0.148 to 0.899, p = 0.028) respectively. CONCLUSIONS: The anatomy of LA, especially morphology of pulmonary veins, seems to be one of the predictors of clinical outcome after CA for paroxysmal AF. In non-paroxysmal AF LA anatomy is less relevant in prediction of clinical outcome.

Multivariate Analysis of Correspondence between Left Atrial Volumes Assessed by Echocardiography and 3-Dimensional Electroanatomic Mapping in Patients with Atrial Fibrillation.

BACKGROUND: Left atrial (LA) enlargement is a predictor of worse outcome after catheter ablation for atrial fibrillation (AF). Widely used two-dimensional (2D)-echocardiography is inaccurate and underestimates real LA volume (LAV). We hypothesized that baseline clinical characteristics of patients can be used to adjust 2D-ECHO indices of LAV in order to minimize this disagreement. METHODS: The study enrolled 535 patients (59 ± 9 years; 67% males; 43% paroxysmal AF) who underwent catheter ablation for AF in three specialized centers. We investigated multivariately the relationship between 2D-echocardiographic indices of LA size, specifically LA diameter in M-mode in the parasternal long-axis view (LAD), LAV assessed by the prolate-ellipsoid method (LAVEllipsoid), LAV by the planimetric method (LAVPlanimetry), and LAV derived from 3D-electroanatomic mapping (LAVCARTO). RESULTS: Cubed LAD of 106 ± 45 ml, LAVEllipsoid of 72 ± 24 ml and LAVPlanimetry of 88 ± 30 ml correlated only modestly (r = 0.60, 0.69, and 0.53, respectively) with LAVCARTO of 137 ± 46 ml, which was significantly underestimated with a bias (±1.96 standard deviation) of -31 (-111; +49) ml, -64 (-132; +2) ml, and -49 (-125; +27) ml, respectively; p < 0.0001 for their mutual difference. LA enlargement itself, age, gender, type of AF, and the presence of structural heart disease were independent confounders of measurement error of 2D-echocardiographic LAV. CONCLUSION: Accuracy and precision of all 2D-echocardiographic LAV indices are poor. Their agreement with true LAV can be significantly improved by multivariate adjustment to clinical characteristics of patients.