Partner relationship in couples living with atrial fibrillation

The aim of this thesis was to describe and explore how the partner relationship of patient–partner dyads isaffected following cardiac disease and, in particular, atrial fibrillation (AF) in one of the spouses. The thesis is based on four individual studies with different designs: descriptive (I), explorative (II, IV), and cross-sectional (III). Applied methods comprised a systematic review (I) and qualitative (II, IV) and quantitative methods (III). Participants in the studies were couples in which one of the spouses was afflicted with AF. Coherent with a systemic perspective, the research focused on the dyad as the unit of analysis. To identify and describe the current research position and knowledge base, the data for the systematic review were analyzed using an integrative approach. To explore couples’ main concern, interview data (n=12 couples) in study II were analyzed using classical grounded theory. Associations between patients and partners (n=91 couples) where analyzed through the Actor–Partner Interdependence Model using structural equation modelling (III). To explore couples’ illness beliefs, interview data (n=9 couples) in study IV were analyzed using Gadamerian hermeneutics. Study I revealed five themes of how the partner relationship is affected following cardiac disease: overprotection, communication deficiency, sexual concerns, changes in domestic roles, and adjustment to illness. Study II showed that couples living with AF experienced uncertainty as the common main concern, rooted in causation of AF and apprehension about AF episodes. The theory of Managing Uncertainty revealed the strategies of explicit sharing (mutual collaboration and finding resemblance) and implicit sharing (keeping distance and tacit understanding). Patients and spouses showed significant differences in terms of self-reported physical and mental health where patients rated themselves lower than spouses did (III). Several actor effects were identified, suggesting that emotional distress affects and is associated with perceived health. Patient partner effects and spouse partner effects were observed for vitality, indicating that higher levels of symptoms of depression in patients and spouses were associated with lower vitality in their partners. In study IV, couples’ core and secondary illness beliefs were revealed. From the core illness belief that “the heart is a representation of life,” two secondary illness beliefs were derived: AF is a threat to life, and AF can and must be explained. From the core illness belief that “change is an integral part of life,” two secondary illness beliefs were derived: AF is a disruption in our lives, and AF will not interfere with our lives. Finally, from the core illness belief that “adaptation is fundamental in life,” two secondary illness beliefs were derived: AF entails adjustment in daily life, and AF entails confidence in and adherence to professional care. In conclusion, the thesis result suggests that illness, in terms of cardiac disease and AF, affected and influenced the couple on aspects such as making sense of AF, responding to AF, and mutually incorporating and dealing with AF in their daily lives. In the light of this, the thesis results suggest that clinicians working with persons with AF and their partners should employ a systemic view with consideration of couple’s reciprocity and interdependence, but also have knowledge regarding AF, in terms of pathophysiology, the nature of AF (i.e., cause, consequences, and trajectory), and treatments. A possible approach to achieve this is a clinical utilization of an FSN based framework, such as the FamHC. Even if a formalized FSN framework is not utilized, partners should not be neglected but, rather, be considered a resource and be a part of clinical caring activities. This could be met by inviting partners to take part in rounds, treatment decisions, discharge calls or follow-up visits or other clinical caring activities. Likewise, interventional studies should include the couple as a unit of analysis as well as the target of interventions.

Heart dimensions may influence the occurrence of the heart rate deflection point in highly trained cyclists

To determine whether the heart rate (HR) response to exercise in 21 highly trained cyclists (mean (SD) age 25 (3) years) was related to their heart dimensions. Methods—Before performing an incremental exercise test involving a ramp protocol with workload increases of 25 W/min, each subject underwent echocardiographic evaluation of the following variables: left ventricular end diastolic internal diameter (LVIDd), left ventricular posterior wall thickness at end diastole (LVPWTd), interventricular septal wall thickness at end diastole (IVSTd), left ventricular mass index (LVMI), left atrial dimension (LAD), longitudinal left atrial (LLAD) and right atrial (LRAD) dimensions, and the ratio of early to late (E/A) diastolic flow velocity. Results—The HR response showed a de- flection point (HRd) at about 85% V~ O2MAX in 66.7% of subjects (D group; n = 14) and was linear in 33.3% (NoD group; n = 7). Several echocardiographic variables (LVMI, LAD, LLAD, LRAD) indicative of heart dimensions were similar in each group. However, mean LPWTd (p<0.01) and IVSTd (p<0.05) values were signifi- cantly higher in the D group. Finally, no significant diVerence between groups was found with respect to the E/A. The HR response is curvilinear during incremental exercise in a considerable number of highly trained endurance athletes—that is, top level cyclists. The departure of HR increase from linearity may predominantly occur in athletes with thicker heart walls.

Interatrial block and atrial arrhythmias in centenarians: Prevalence, associations, and clinical implications

Data are lacking on the characteristics of atrial activity in centenarians, including interatrial block (IAB). The aim of this study was to describe the prevalence of IAB and auricular arrhythmias in subjects older than 100 years and to elucidate their clinical implications. We studied 80 centenarians (mean age 101.4 ± 1.5 years; 21 men) with follow-ups of 6–34 months. Of these 80 centenarians, 71 subjects (88.8%) underwent echocardiography. The control group comprised 269 septuagenarians. A total of 23 subjects (28.8%) had normal P wave, 16 (20%) had partial IAB, 21 (26%) had advanced IAB, and 20 (25.0%) had atrial fibrillation/flutter. The IAB groups exhibited premature atrial beats more frequently than did the normal P wave group (35.1% vs 17.4%; P < .001); also, other measurements in the IAB groups frequently fell between values observed in the normal P wave and the atrial fibrillation/flutter groups. These measurements included sex preponderance, mental status and dementia, perceived health status, significant mitral regurgitation, and mortality. The IAB group had a higher previous stroke rate (24.3%) than did other groups. Compared with septuagenarians, centenarians less frequently presented a normal P wave (28.8% vs 53.5%) and more frequently presented advanced IAB (26.3% vs 8.2%), atrial fibrillation/flutter (25.0% vs 10.0%), and premature atrial beats (28.3 vs 7.0%) (P < .01). Relatively few centenarians (<30%) had a normal P wave, and nearly half had IAB. Our data suggested that IAB, particularly advanced IAB, is a pre–atrial fibrillation condition associated with premature atrial beats. Atrial arrhythmias and IAB occurred more frequently in centenarians than in septuagenarians.

Oral anticoagulation in octogenarians with atrial fibrillation

Vitamin K antagonists (VKAs) are still largely employed, even in nonvalvular atrial fibrillation (AF). Our aim was to study the clinical profile of octogenarians treated with oral anticoagulation and to study the effect of age on the quality of VKAs anticoagulation. Data are from a prospective national registry in an adult Spanish population of nonvalvular AF. We included 1637 patients who had been receiving VKAs for at least 6 months before enrolment. Mean age was 73.8 ± 9.4 years. Patients aged > 80 years (N = 429) had a high risk profile with higher risk of stroke and bleeding than younger patients; CHA2DS2-VASc (Cardiac failure, Hypertension, Age > 74, Diabetes, Stroke, Vascular disease, Age 65–74 years, and Sex category) 4.5 ± 1.3 vs. 3.5 ± 1.6, p < 0.001, HAS-BLED (Hypertension, Abnormal renal/liver function, Stroke, Bleeding history or predisposition, Labile international normalized ratio, Elderly (> 64 years), Drugs/alcohol concomitantly) 2.4 ± 0.9 vs. 1.9 ± 1.1, p < 0.001. Creatinine clearance was lower in octogenarians than in younger patients (54.3 ± 16.1 ml/min vs. 69.5 ± 23.7 ml/min, p < 0.001) and severe renal disease with creatinine clearance < 30 ml/min was more frequent in octogenarians (5.2% vs. 2.2%, p < 0.001). In patients treated with VKAs (N = 1637), the international normalized ratio values of the 6 months previous to enrollment were similar in all age quartiles, as was the time in the therapeutic range. In this large registry octogenarians with nonvalvular AF had high risk of stroke and bleeding and frequent renal disease. VKAs anticoagulation quality was similar in octogenarians and in younger patients.

Left atrial appendage: anatomy and imaging landmarks pertinent to percutaneous transcatheter occlusion

Percutaneous left atrial appendage (LAA) closure represents a complementary option and effective treatment for patients at risk of thromboembolism, especially in patients for whom it may be difficult to achieve satisfactory anticoagulation control or where anticoagulation treatment is not possible or desirable. Effective and safe transcatheter LAA occlusion requires a detailed knowledge of crucial anatomic landmarks and endocardial morphologic variants of the LAA and its neighbouring structures.1 ,2 w1–w3 Our aim in this article is to provide the basic anatomic information that is important for the interventional cardiologist to know when planning an LAA occlusion procedure.

Left atrial anatomy relevant to catheter ablation

The rapid development of interventional procedures for the treatment of arrhythmias in humans, especially the use of catheter ablation techniques, has renewed interest in cardiac anatomy. Although the substrates of atrial fibrillation (AF), its initiation and maintenance, remain to be fully elucidated, catheter ablation in the left atrium (LA) has become a common therapeutic option for patients with this arrhythmia. Using ablation catheters, various isolation lines and focal targets are created, the majority of which are based on gross anatomical, electroanatomical, and myoarchitectual patterns of the left atrial wall. Our aim was therefore to review the gross morphological and architectural features of the LA and their relations to extracardiac structures. The latter have also become relevant because extracardiac complications of AF ablation can occur, due to injuries to the phrenic and vagal plexus nerves, adjacent coronary arteries, or the esophageal wall causing devastating consequences.

Edoxaban versus enoxaparin–warfarin in patients undergoing cardioversion of atrial fibrillation (ENSURE-AF): a randomised, open-label, phase 3b trial

Background Edoxaban, an oral factor Xa inhibitor, is non-inferior for prevention of stroke and systemic embolism in patients with atrial fibrillation and is associated with less bleeding than well controlled warfarin therapy. Few safety data about edoxaban in patients undergoing electrical cardioversion are available. Methods We did a multicentre, prospective, randomised, open-label, blinded-endpoint evaluation trial in 19 countries with 239 sites comparing edoxaban 60 mg per day with enoxaparin–warfarin in patients undergoing electrical cardioversion of non-valvular atrial fibrillation. The dose of edoxaban was reduced to 30 mg per day if one or more factors (creatinine clearance 15–50 mL/min, low bodyweight [≤60 kg], or concomitant use of P-glycoprotein inhibitors) were present. Block randomisation (block size four)—stratified by cardioversion approach (transoesophageal echocardiography [TEE] or not), anticoagulant experience, selected edoxaban dose, and region—was done through a voice-web system. The primary efficacy endpoint was a composite of stroke, systemic embolic event, myocardial infarction, and cardiovascular mortality, analysed by intention to treat. The primary safety endpoint was major and clinically relevant non-major (CRNM) bleeding in patients who received at least one dose of study drug. Follow-up was 28 days on study drug after cardioversion plus 30 days to assess safety. This trial is registered with ClinicalTrials.gov, number NCT02072434. Findings Between March 25, 2014, and Oct 28, 2015, 2199 patients were enrolled and randomly assigned to receive edoxaban (n=1095) or enoxaparin–warfarin (n=1104). The mean age was 64 years (SD 10·54) and mean CHA2DS2-VASc score was 2·6 (SD 1·4). Mean time in therapeutic range on warfarin was 70·8% (SD 27·4). The primary efficacy endpoint occurred in five (<1%) patients in the edoxaban group versus 11 (1%) in the enoxaparin–warfarin group (odds ratio [OR] 0·46, 95% CI 0·12–1·43). The primary safety endpoint occurred in 16 (1%) of 1067 patients given edoxaban versus 11 (1%) of 1082 patients given enoxaparin–warfarin (OR 1·48, 95% CI 0·64–3·55). The results were independent of the TEE-guided strategy and anticoagulation status. Interpretation ENSURE-AF is the largest prospective randomised clinical trial of anticoagulation for cardioversion of patients with non-valvular atrial fibrillation. Rates of major and CRNM bleeding and thromboembolism were low in the two treatment groups. Funding Daiichi Sankyo provided financial support for the study. © 2016 Elsevier Ltd

Development of a patient-specific model for stroke risk assessment in atrial fibrillation patients

Atrial fibrillation is associated with a five-fold increase in the risk of cerebrovascular events,being responsible of 15-18% of all strokes.The morphological and functional remodelling of the left atrium caused by atrial fibrillation favours blood stasis and, consequently, stroke risk. In this context, several clinical studies suggest that stroke risk stratification could be improved by using haemodynamic information on the left atrium (LA) and the left atrial appendage (LAA). The goal of this study was to develop a personalized computational fluid-dynamics (CFD) model of the left atrium which could clarify the haemodynamic implications of atrial fibrillation on a patient specific basis. The developed CFD model was first applied to better understand the role of LAA in stroke risk. Infact, the interplay of the LAA geometric parameters such as LAA length, tortuosity, surface area and volume with the fluid-dynamics parameters and the effects of the LAA closure have not been investigated. Results demonstrated the capabilities of the CFD model to reproduce the real physiological behaviour of the blood flow dynamics inside the LA and the LAA. Finally, we determined that the fluid-dynamics parameters enhanced in this research project could be used as new quantitative indexes to describe the different types of AF and open new scenarios for the patient-specific stroke risk stratification.

CO2-EVAR: An innovative approach to Automated Carbon Dioxide Angiography during Endovascular Abdominal Aortic Aneurysm repair

Objectives CO2-EVAR was proposed for treatment of AAA especially in patients with CKD. Issues regarding standardization, such as visualization of lowest renal artery (LoRA) and quality image in angiographies performed from pigtail or introducer-sheath, are still unsolved. Aim of the study was to analyze different steps of CO2-EVAR to create an operative protocol to standardize the procedure. Methods Patients undergoing CO2-EVAR were prospectively enrolled in 5 European centers (2018-2021). CO2-EVAR was performed using an automated injector. LoRA visualization and image quality (1-4) were analyzed and compared at different procedure steps: preoperative CO2-angiography from Pigtail/Introducer-sheath (1st Step), angiographies from Pigtail at 0%,50%,100% main body (MB) deployment (2nd Step), contralateral hypogastric artery (CHA) visualization with CO2 injection from femoral Introducer-sheath (3rd Step) and completion angiogram from Pigtail/Introducer-sheath (4th Step). Intra-/postoperative adverse events were evaluated. Results Sixty-five patients undergoing CO2-EVAR were enrolled, 55/65(84.5%) male, median age 75(11.5) years. Median ICM was 20(54)cc; 19/65(29.2%) procedures were performed with 0-iodine. 1st Step: median image quality was significantly higher with CO2 injected from femoral introducer [Pigtail2(3)vs.3(3)Introducer,p=.008]. 2nd Step: LoRA was more frequently detected at 50% (93%vs.73.2%, p=.002) and 100% (94.1%vs.78.4%, p=.01) of MB deployment compared with first angiography from Pigtail; image quality was significantly higher at 50% [3(3)vs.2(3),p=<.001] and 100% [4(3) vs.2(3),p=.001] of MB deployment. CHA was detected in 93% cases (3rd Step). Mean image quality was significantly higher when final angiogram (4th Step) was performed from introducer (Pigtail2.6±1.1vs.3.1±0.9Introducer,p=<.001). Rates of intra-/postoperative adverse events (pain,vomit,diarrhea) were 7.7% and 12.5%. Conclusions Preimplant CO2-angiography should be performed from Introducer-sheath. MB steric bulk during its deployment should be used to improve image quality and LoRA visualization with CO2. CHA can be satisfactorily visualized with CO2. Completion CO2-angiogram should be performed from femoral Introducer-sheath. This operative protocol allows to perform CO2-EVAR with minimal ICM and low rate of mild complications.

Left Ventricle Modification After Endovascular Aortic Repair

INTRODUCTION Endograft deployment is a well-known cause of arterial stiffness increase as well as arterial stiffness increase represent a recognized cardiovascular risk factor. A harmful effect on cardiac function induced by the endograft deployment should be investigated. Aim of this study was to evaluate the impact of endograft deployment on the arterial stiffness and cardiac geometry of patients treated for aortic aneurysm in order to detect modifications that could justify an increased cardiac mortality at follow-up. MATHERIALS AND METHODS Over a period of 3 years, patients undergoing elective EVAR for infrarenal aortic pathologies in two university centers in Emilia Romagna were examined. All patients underwent pre-operative and six-months post-operative Pulse Wave Velocity (PWV) examination using an ultrasound-based method performed by vascular surgeons together with trans-thoracic echocardiography examination in order to evaluate cardiac chambers geometry before and after the treatment. RESULTS 69 patients were enrolled. After 36 months, 36 patients (52%) completed the 6 months follow-up examination.The ultrasound-based carotid-femoral PWV measurements performed preoperatively and 6 months after the procedure revealed a significant postoperative increase of cf-PWV (11,6±3,6 m/sec vs 12,3±8 m/sec; p.value:0,037).Postoperative LVtdV (90±28,3 ml/m2 vs 99,1±29,7 ml/m2; p.value:0.031) LVtdVi (47,4±15,9 ml/m2 vs 51,9±14,9 ml/m2; p.value:0.050), IVStd (12±1,5 mm vs 12,1±1,3 mm; p.value:0,027) were significantly increased if compared with preoperative measures.Postoperative E/A (0,76±0,26 vs 0,6±0,67; p.value:0,011), E’ lateral (9,5±2,6 vs 7,9±2,6; p.value:0,024) and A’ septal (10,8±1,5 vs 8,9±2; p.value0,005) were significantly reduced if compared with preoperative measurements CONCLUSION The endovascular treatment of the abdominal aorta causes an immediate and significant increase of the aortic stiffness.This increase reflects negatively on patients’ cardiac geometry inducing left ventricle hypertrophy and mild diastolic disfunction after just 6 months from endograft’s implantation.Further investigations and long-term results are necessary to access if this negative remodeling could affect the cardiac outcome of patient treated using the endovascular approach.

Late onset spinal cord ischemia after thoracoabdominal aortic aneurysm open repair

The aim of this study is to evaluate if spinal cord ischemia (SCI), especially its late presentation, and can be correlated to the results of intraoperative evoked potential monitoring (IOM). Methods. This study is a physician-initiated, retrospective, single-center, non-randomized study. Data from all patients undergoing a thoracoabdominal aortic aneurysm surgical repair (TAAA SR) between January 2016 and March 2020 IOM was collected and analyzed. Results. During the study period, 261 patients underwent TAAA SR with MEP/SSEPs monitoring [190 males, 73%; median age 65 (57-71)]. Thirty-seven patients suffered from SCI, for an overall rate of 14% (permanent 9%). When stratifying patients according to the SCI onset, 18 patients presented with an early (11 permanent) and 19 with a late SCI (<24h) (11 permanent). Of 261 patients undergoing TAAA SR with IOM, 15 were excluded due to changes in the upper extremity motor evoked potentials. For the remaining 246, the association between SCI and IOM was investigated: only irreversible IOM loss without peripheral changes have been found to be a risk factor for late onset SCI (p=.006). Furthermore, given that no statistical differences were found between the two groups when no IOM changes were recorded (p=.679), this situation cannot reliably rule out any SCI in our cohort. Independent risk factors for late spinal cord ischemia onset found at multivariate analysis were smoking history (p=.008), BMI>28 (p=.048) and TAAA extent II (p=.009). The irreversible MEP change without peripheral showed a trend of significance (p=.052). Conclusions. Evoked potential intraoperative monitoring is an important adjunct during thoracoabdominal aortic open repair to predict and possibly prevent spinal cord ischemia. Irreversible IOM loss without peripheral changes was predictive of late SCI, therefore more attention should be paid to the postoperative management of this subgroup of patients.

Computational modeling of human atrial cardiomyocytes: integration of electro-mechanical & mechano-electric feedback pathways

The cardiomyocytes are very complex consisting of many interlinked non-linear regulatory mechanisms between electrical excitation and mechanical contraction. Thus given a integrated electromechanically coupled system it becomes hard to understand the individual contributor of cardiac electrics and mechanics under both physiological and pathological conditions. Hence, to identify the causal relationship or to predict the responses in a integrated system the use of computational modeling can be beneficial. Computational modeling is a powerful tool that provides complete control of parameters along with the visibility of all the individual components of the integrated system. The advancement of computational power has made it possible to simulate the models in a short timeframe, providing the possibility of increased predictive power of the integrated system. My doctoral thesis is focused on the development of electromechanically integrated human atrial cardiomyocyte model with proper consideration of feedforward and feedback pathways.

Development of a hydrogel construct to prevent endoleaks occurrence following endovascular abdominal aortic aneurysm repair

Abdominal aortic aneurysm is the pathological dilation of the abdominal tract of the aorta and, if left untreated, could undergo rupture with a mortality rate of up to 90%. EVAR is the most common method for AAA treatment consisting in the internal coverage of the aorta with a metallic stent to isolate the aneurysmatic segment from the systemic circulation. Although EVAR technical success rate is high, reinterventions are common. Among the causes of reinterventions typeII endoleaks are the most frequent and consist in retrograde blood flow into the aneurysmal sac from collateral aortic branches. Continued perfusion of the aneurysm sac may lead to aneurysm rupture, therefore AAA sac embolization is performed using metallic coils. However, the presence of artifacts caused by the presence of metallic coils is a limitation because they are radiopaque and can hamper the endoleak during imaging follow-up. This study is aimed at developing a biocompatible hydrogel that could be injected into the aneurysmal sac and may allow a selective intraprocedural sac embolization to reduce post procedural typeII endoleak and eventual AAA rupture. P(BT75BSI25) was synthesized by polycondensation and its biocompatibility tested to assess whether the polymers had no toxic effects. HUVEC cell line was used to mimic the environment in which the polymer would be in contact with, PBS was used as a positive control and MTT assay was performed to evaluate cellular viability after being in contact with the hydrogel. MTT assay showed no significant difference between PBS and P(BT75BSI25), thus the polymer is biocompatible, as confirmed by the analysis of apoptosis by flow cytometry. An aromatic copolymer was obtained via polycondensation and was found to be biocompatible in contact with endothelial cells. This suggests that the hydrogel could be potentially used in the clinical setting for the treatment of type II endoleak after EVAR.

Saphenous vein graft bypass in the treatment of giant cavernous sinus aneurysms: report of two cases

Two cases of giant intracavernous aneurysms treated by high flow bypass with saphenous vein graft between the external carotid artery (ECA) and branches of the middle cerebral artery (MCA) are presented. Very often these aneurysms are unclippable because they are fusiform or have a large neck. Occlusion of the internal carotid artery (ICA) is the treatment of choice in many cases. This procedure has however a high risk of brain infarction. Revascularization of the brain by extra-intracranial anastomosis between the superficial temporal artery (STA) and branches of the MCA is frequently performed. This procedure provides however a low flow bypass and brain infarction may occur. We report two cases of giant cavernous sinus aneurysms treated by high flow bypass and endovascular balloon occlusion of the ICA. Immediate high flow revascularization of MCA branches was achieved and the patients showed no ischemic events. Follow-up of 8 and 14 months after operation shows patency of the venous graft and no neurological deficits. Angiographic control examination showed complete aneurysm occlusion in both cases.

Fibrodysplasia ossificans progressiva: case report

Fibrodysplasia ossificans progressiva is a rare genetic disease characterized by widespread soft tissue ossification and congenital stigmata of the extremities. We report on a male child followed for ten years since the age of 3 years and 9 months, when the diagnosis was made. He was born with bilateral hypoplasic hallux valgus and ventricular septal defect, corrected by transsternal approach when 32 months old. Restriction of neck mobility followed and foci of ectopic ossification appeared. Four crises of disease exacerbation were treated with oral prednisone and/or other antiinflammatory drugs. Sodium etidronate 5 to 10 mg/kg/day was prescribed intermittently during about six years but was discontinued due to osteopenia. The disease course has been relentless, with severe movement restriction including the chest wall. A review showed few similar case reports in the Brazilian literature. We revisit the criteria for diagnosis and the essentials of management and treatment.