Understanding the hemodynamics of the cardiovascular system and associated diseases is important for mitigating health risks. We applied flow diagnostic techniques to investigate pulsatile flow characteristics past sidewall cavities, which have implications to two biomedical problems in the cardiovascular system: sidewall aneurysms and the left atrial appendage. Superhydrophobically-coated mesh diverters and synthetic slippery surfaces were studied for their effects on flow diversion and cavity flow enhancements. The study of pulsatile flow over a coated mesh diverter showed that the formation of the primary vortex was prevented which prevents flow stagnation and downwash flow in the cavity. The second study indicates that the healthy heart cycle is essential to reducing flow stasis inside the left atrial appendage. After applying a synthetic slippery surface to the interior of a side wall cavity model, this surface reduced the wall shear stress and allowed vortical flow to reach deeper into the cavity.

No description available.

<p>Stroke is a devastating event for a patient. Patients undergoing cardiac surgery are at risk of both peri-operative and delayed stroke. This thesis comprises 8 chapters that highlight the rate of stroke in cardiac surgery patients and its risk predictors. It justifies the need for a randomized controlled trial of left atrial appendage (LAA) occlusion on top of usual antithrombotic therapy for stoke prevention in patients with atrial fibrillation or flutter.</p> <p>Chapter 1 is a preface that provides the rationale for undertaking each of the studies included within this thesis.</p> <p>Chapter 2 presents a large cohort study that examines the predictors of early and long-term stroke in patients undergoing cardiac surgery with emphasis on the impact of atrial fibrillation as well as the CHADS₂ score.</p> <p>Chapter 3 has been published in the journal <em>Circulation </em>in a modified form. A review of the current literature is presented, highlighting that although LAA occlusion holds promise for stroke prevention in AF, there is currently insufficient evidence that it can replace the gold standard of oral anticoagulation.</p> <p>Chapter 4 is a long-term follow-up study of the first Left Atrial Appendage Occlusion Study. This trial included patients undergoing coronary artery bypass grafting with or without AF. By performing a long-term follow-up of these patients, an estimate of stroke risk and risk of developing new AF was obtained.</p> <p>In Chapter 5, the results of LAAOS II are presented. This registry and pilot trial was used to assess the rate of recruitment into a novel design of a trial comparing LAA occlusion to antithrombotic therapy, LAA amputation safety, and the rate of a composite outcome of death, myocardial infarction, stroke, non-cerebral systemic emboli, and major bleeding.</p> <p>Chapter 6 presents the design for the LAAOS III trial. The data presented in the previous chapters is used to create the definitive trial of LAA occlusion on top of usual antithrombotic therapy using a prospective, randomized open trial with blinded end-point study (i.e., PROBE) design.</p> <p>Chapter 7 presents the health economic analysis plan for LAAOS III.</p> <p>Finally, Chapter 8 presents the conclusion, limitations, and implications of the research presented in my PhD thesis</p> / Doctor of Philosophy (PhD)

No description available.

Aims: The clinical role of the left atrial (LA) hypertension in patients with atrial fibrillation (AF) and its role as predictor in those undergoing pulmonary vein (PV) isolation is still unknown. The aim of the present study was to analyze the role of LA pressure in patients with nonvalvular AF who underwent PV isolation and its implication for AF catheter ablation. Methods: Consecutive patients with drug resistant AF who underwent PV isolation at San Maurizio Regional Hospital of Bolzano (Italy) as index procedure were included in this analysis. Results: A total of 132 consecutive patients (97 males, 73%; mean age 58.0 ± 13.2 years) were included in the analysis. Eleven patients (8%) underwent radiofrequency ablation and 121 (92%) cryoballoon ablation. Higher LA pressures were found in 54 patients (40.9%). At a mean follow up of 14.3 ± 8.2 months (median 12 months), the success rate without antiarrhythmic therapy was 65.9% (87/132; considering the blanking period). Female gender and continuous mean LA pressure were significantly associated with AF recurrence and remained significant on multivariable Cox analysis (respectively, HR 1.845, 1.00–3.40, p = 0.05 and HR 1.066, 1.002–1.134, p = 0.04). We identified a LA mean pressure of >15 mmHg as ideal cutoff and constructed a model to predict AF recurrence which fitted with a concordance index (C-index) of 0.65 (95% CI 0.56–0.75), logrank score p = 0.003.

The general purpose of this thesis is to establish the ability of Speckle Tracking Echocardiography (STE) in assessing left atrial (LA) response to pressure and volume overload respectively in aortic stenosis (AS) and mitral regurgitation (MR), and to evaluate its accuracy in predicting LA and right ventricular (RV) fibrosis in patients with end-stage heart failure (HF) undergoing heart transplantation (HTx). I demonstrated that assessment of left ventricular (LV) long axis systolic velocity and amplitude of excursion is more sensitive than simple determination of ejection fraction (EF) for revealing the beneficial impact of MR surgery on overall LV systolic performance. Severe symptomatic AS is associated with LA enlargement and compromised mechanical function with a high incidence of peri-operative atrial fibrillation (AF). Valve replacement reverses these abnormalities and regains normal atrial function, a behaviour which is directly related to the severity of pre-operative LV outflow tract obstruction. Early identification of LA size and function disturbances, as shown by myocardial strain measurements might contribute to better patient’s recruitment for a safe valve replacement. In late stage HF patients, the right ventricle is enlarged, with reduced systolic function due to significant myocardial fibrosis. RV free wall myocardial deformation is the most accurate function measure that correlates with the extent of RV myocardial fibrosis and functional capacity. In patients with preserved EF, severe MR masks LV and LA myocardial dysfunction and correlates with symptoms and post-operative cavity function instability. Three months after MVR, the underlying myocardial disturbances are unmasked suggesting that most pre-operative measurements are subject to loading conditions. Finally LA volume and PALS remain the main predictors of post-operative AF, thus should be used for stratifying surgical risk. STE has been shown to accurately determine the severity of impairment of LA myocardial function shown by suppressed PALS which was the strongest predictor of the presence and extent of fibrosis, over and above other structure and function parameters. These findings may assist in better stratifying patients with end stage HF and identifying particularly those requiring HTx.

No description available.

Le système nerveux autonome cardiaque est devenu une cible dans les thérapies ablatives de la fibrillation auriculaire. Nous avons étudié les voies de communication et la fonction des plexus ganglionnaires (PG) de l'oreillette gauche (PGOG) afin de clarifier la validité physiopathologique des méthodes de détection et des thérapies impliquant ces groupes de neuronnes. Méthodes: Vingt-deux chiens ont subi une double thoracotomie et ont été instrumentés avec des plaques auriculaires épidcardiques de multiélectrodes. Une stimulation électrique (2 mA, 15 Hz) des PGOG a été réalisée à l'état basal et successivement après: 1) une décentralisation vagale, 2) l'ablation par radiofréquence des plexus péri-aortiques et de la veine cave supérieure (Ao/VCS) et 3) l'ablation du PG de l'oreillette droite (PGOD). Ces procédures de dénervation ont été réalisées suivant une séquence antérograde (n = 17) ou rétrograde (n = 5). Résultats: Chez 17 des 22 animaux, la stimulation des PGOG a induit une bradycardie sinusale (149 ± 34 bpm vs 136 ± 28 bpm, p < 0.002) et des changements de repolarization (ΔREPOL) auriculaires isointégrales. Dans le groupe des ablations antérogrades, les réponses aux stimulations vagales ont été supprimées suite à la décentralisation vagale chez un seul animal, par l'ablation des plexus Ao/VCS dans 4 cas et par l'ablation du PGOG dans 5 autres animaux. Des changements ont persisté tout au long chez 2 chiens. La valeur de surface des ΔREPOL a diminué avec les dénervations séquentielles, passant de 365 ± 252 mm2 en basale à 53 ± 106 mm2 après l'ablation du PGOD (p < 0.03). Dans le groupe de dénervation rétrograde, les changements de repolarisation et chronotropiques ont été supprimés suite à l'ablation du PGOD chez deux chiens et suite à l'ablation Ao/VCS chez trois. La valeur de surface du ΔREPOL a aussi diminué après l'ablation du PGOD (269±144mm2 vs 124±158mm2, p<0.05). Conclusion: Les PGOD sont identifiables en préablation par la réponse bradycardique à la stimulation directe dans la plupart des cas. Le PGOD semble former la principale, mais non la seule, voie de communication avec le nœud sinusal. Ces résultats pourraient avoir des implications dans le traitement de la FA par méthodes ablatives. / The cardiac autonomic nervous system has recently become the target of ablative therapy in the treatment of atrial fibrillation. We investigated the pathways and function of the left atrial ganglionated plexus (LAGP) to clarify the pathophysiologic validity of therapies involving this cluster of neurons. Methods: Twenty-two bilaterally thoracotomized canines were instrumented with atrial epicardial plaques. LAGP stimulation was performed in the basal state and successively following 1) vagal decentralization, 2) radiofrequency ablation of the peri-aortic/superior vena caval (Ao/SVC) plexi, and 3) of the right atrial ganglionated plexus (RAGP). Denervation was carried out in either the aforementioned order (n=17, antegrade) or reversed (n=5, retrograde). Results: In 17 of 22 animals, LAGP stimulation induced a sinus bradycardia (149±34bpm to 136±28bpm, p<0.002) and atrial isointegral repolarization changes (REPOL∆). In the antegrade group, response was suppressed by vagal decentralization (n=1), Ao/SVC plexi ablation (n=4), and RAGP ablation (n=5). Changes persisted throughout in 2 canines. Surface area of REPOL∆ diminished with successive denervation, from 365±252 at baseline to 53±106mm2 following RAGP ablation (p<0.03). With retrograde denervation, chronotropic and repolarisation changes were suppressed following RAGP ablation in two canines, and following Ao/SVC ablation in three. Surface area of REPOL∆ diminished following RAGP ablation as well (269±144mm2 vs 124±158mm2, p<0.05). Conclusion: The LAGP can be identified intraoperatively by the bradycardic response to direct stimulation in most cases. The RAGP appears to be the primary, but not the only, gateway to the sinus node. These results could have important clinical implications relating to ablative treatment of atrial fibrillation.

Le système nerveux autonome cardiaque est devenu une cible dans les thérapies ablatives de la fibrillation auriculaire. Nous avons étudié les voies de communication et la fonction des plexus ganglionnaires (PG) de l'oreillette gauche (PGOG) afin de clarifier la validité physiopathologique des méthodes de détection et des thérapies impliquant ces groupes de neuronnes. Méthodes: Vingt-deux chiens ont subi une double thoracotomie et ont été instrumentés avec des plaques auriculaires épidcardiques de multiélectrodes. Une stimulation électrique (2 mA, 15 Hz) des PGOG a été réalisée à l'état basal et successivement après: 1) une décentralisation vagale, 2) l'ablation par radiofréquence des plexus péri-aortiques et de la veine cave supérieure (Ao/VCS) et 3) l'ablation du PG de l'oreillette droite (PGOD). Ces procédures de dénervation ont été réalisées suivant une séquence antérograde (n = 17) ou rétrograde (n = 5). Résultats: Chez 17 des 22 animaux, la stimulation des PGOG a induit une bradycardie sinusale (149 ± 34 bpm vs 136 ± 28 bpm, p < 0.002) et des changements de repolarization (ΔREPOL) auriculaires isointégrales. Dans le groupe des ablations antérogrades, les réponses aux stimulations vagales ont été supprimées suite à la décentralisation vagale chez un seul animal, par l'ablation des plexus Ao/VCS dans 4 cas et par l'ablation du PGOG dans 5 autres animaux. Des changements ont persisté tout au long chez 2 chiens. La valeur de surface des ΔREPOL a diminué avec les dénervations séquentielles, passant de 365 ± 252 mm2 en basale à 53 ± 106 mm2 après l'ablation du PGOD (p < 0.03). Dans le groupe de dénervation rétrograde, les changements de repolarisation et chronotropiques ont été supprimés suite à l'ablation du PGOD chez deux chiens et suite à l'ablation Ao/VCS chez trois. La valeur de surface du ΔREPOL a aussi diminué après l'ablation du PGOD (269±144mm2 vs 124±158mm2, p<0.05). Conclusion: Les PGOD sont identifiables en préablation par la réponse bradycardique à la stimulation directe dans la plupart des cas. Le PGOD semble former la principale, mais non la seule, voie de communication avec le nœud sinusal. Ces résultats pourraient avoir des implications dans le traitement de la FA par méthodes ablatives. / The cardiac autonomic nervous system has recently become the target of ablative therapy in the treatment of atrial fibrillation. We investigated the pathways and function of the left atrial ganglionated plexus (LAGP) to clarify the pathophysiologic validity of therapies involving this cluster of neurons. Methods: Twenty-two bilaterally thoracotomized canines were instrumented with atrial epicardial plaques. LAGP stimulation was performed in the basal state and successively following 1) vagal decentralization, 2) radiofrequency ablation of the peri-aortic/superior vena caval (Ao/SVC) plexi, and 3) of the right atrial ganglionated plexus (RAGP). Denervation was carried out in either the aforementioned order (n=17, antegrade) or reversed (n=5, retrograde). Results: In 17 of 22 animals, LAGP stimulation induced a sinus bradycardia (149±34bpm to 136±28bpm, p<0.002) and atrial isointegral repolarization changes (REPOL∆). In the antegrade group, response was suppressed by vagal decentralization (n=1), Ao/SVC plexi ablation (n=4), and RAGP ablation (n=5). Changes persisted throughout in 2 canines. Surface area of REPOL∆ diminished with successive denervation, from 365±252 at baseline to 53±106mm2 following RAGP ablation (p<0.03). With retrograde denervation, chronotropic and repolarisation changes were suppressed following RAGP ablation in two canines, and following Ao/SVC ablation in three. Surface area of REPOL∆ diminished following RAGP ablation as well (269±144mm2 vs 124±158mm2, p<0.05). Conclusion: The LAGP can be identified intraoperatively by the bradycardic response to direct stimulation in most cases. The RAGP appears to be the primary, but not the only, gateway to the sinus node. These results could have important clinical implications relating to ablative treatment of atrial fibrillation.

Contexte: La maladie de Fabry (MF) se caractérise par l'accumulation de sphingolipides dans de multiples organes dont l'oreillette gauche (OG). La littérature existante ne permet pas d'établir si les fonctions réservoir, conduit et pompe de l'OG étudiées par échocardiographie de suivi des marqueurs acoustiques (speckle-tracking echocardiography, STE) sont affectées dans la MF et si la thérapie de remplacement enzymatique (TRE) permet d'améliorer la fonction de l'OG. Méthodes: Dans cette étude de cohorte rétrospective, la déformation, le taux de déformation et les volumes phasiques de l'OG ont été étudiés chez 50 patients atteints de la MF et comparés à 50 contrôles sains. Résultats: Les trois fonctions phasiques de l'OG étaient altérées. La déformation positive maximale (fonction réservoir) était de 38,9 ± 14,9 % vs. 46,5 ± 10,9 % (p=0,004) et la déformation télédiastolique (fonction pompe) était de 12,6 ± 5,9 % vs. 15,6 ± 5,3 % (p=0,010). Chez 15 patients ayant débuté la TRE pendant l'étude, la majorité des paramètres de fonction de l'OG se sont améliorés après un suivi d'un an (déformation positive maximale de 32,0 ± 13,5 % à 38,0 ± 13,5 %; p=0,006) alors qu'il y a eu une tendance vers une détérioration des paramètres chez 15 patients n'ayant jamais reçu de traitement (déformation positive maximale de 47,3 ± 10,8 % à 41,3 ± 9,3 %; p=0,058). Neuf patients atteints de la MF (21%) ont développé une fibrillation auriculaire ou un accident vasculaire cérébral pendant un suivi de quatre ans. La déformation positive maximale et la déformation protodiastolique étaient plus fortement associés aux événements cliniques que les paramètres cliniques et les paramètres échocardiographiques standards. Conclusions: Les fonctions réservoir, conduit et pompe de l'OG par STE étaient affectées dans la MF. La TRE a permis d'améliorer la fonction de l'OG. Les paramètres de déformation de l'OG étaient associés à la survenue de fibrillation auriculaire et d'accidents vasculaires cérébraux. / Background: Fabry disease (FD) is characterized by the accumulation of sphingolipids in multiple organs including the left atrium (LA). It is uncertain if the LA reservoir, conduit and contractile functions evaluated by speckle-tracking echocardiography are affected in Fabry cardiomyopathy and whether enzyme replacement therapy can improve LA function. Methods: In this retrospective cohort study, LA strain, strain rates and phasic LA volumes were studied in 50 FD patients and compared to 50 healthy controls. Results: All three LA phasic functions were altered. The peak positive strain (reservoir function) was 38.9 ± 14.9 % vs. 46.5 ± 10.9 % (p=0.004) and the late diastolic strain (contractile function) was 12.6 ± 5.9 % vs. 15.6 ± 5.3 % (p=0.010). In 15 patients who started enzyme replacement therapy during the study, most of the LA parameters improved at one-year follow-up (peak positive strain from 32.0 ± 13.5 % to 38.0 ± 13.5 %; p=0.006) whereas there was a trend towards deterioration in 15 patients who never received treatment (peak positive strain from 47.3 ± 10.8 % to 41.3 ± 9.3 %; p=0.058). Nine FD patients (21%) experienced new-onset atrial fibrillation or stroke during four-year follow-up. By univariate analysis, peak positive strain and early diastolic strain demonstrated significant associations with clinical events, surpassing conventional echocardiographic parameters and clinical characteristics. Conclusions: Left atrial reservoir, conduit and contractile functions by speckle-tracking echocardiography were all affected in FD. Enzyme replacement therapy improved LA function. Left atrial strain parameters were associated with atrial fibrillation and stroke.