| 1. |
- Boles, Usama, 1974-
(författare)
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Insight into coronary artery ectasia
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background:Coronary artery ectasia (CAE) is defined as a diffuse dilatation of the epicardial coronary arteries exceeding 1.5 folds the diameter of the normal adjacent arterial segment and/ or the remaining non-dilated part of the same artery. (1) The incidence of CAE has been variably reported between different nations and ranges between 1.4 -10 % (2-5). This wide range of variability is related to many factors including diverse definition of CAE, geographical distribution, association with other conditions (i.e. inflammatory, congenital or atherosclerosis) hence the existent uncertainty about disease burden and prevalence. (6) The main pathophysiology of CAE is initially understood to be part of atherosclerosis, (3) yet others reported the non-atherosclerotic nature of the disease. (2,7) The exact disease pathophysiology, prognosis and clinical outcome are not well studied; particularly the isolated, non-atherosclerotic, form of the disease has not been fully determined nor well identified. Methods:In paper 1, we examined the clinical presentation, prevalence and cardiovascular risk profile of the CAE patients in acute myocardial infarction (MI). We investigated the inflammatory response and short-term outcome in CAE patients of 3,321 acute consecutive MI patients who underwent primary PCI in two different centres in the UK (Royal Free Hospital, London and Norfolk, and Norwich University Hospital) between January 2009 and August 2012.In paper 2, we studied the personalised lipid profile and immune-inflammatory response in CAE patients from two different destinations (16 patients, mean age 64.9 ± 7.3 years, 6 female) Umea, Sweden and Letterkenny, Ireland. The lipidomic profile was compared with 26 control group (mean age 59.2 ± 6.6, 7 female) with normal coronary arteries.In paper 3, the plasma levels of 16 CAE (mean age 64.9 ± 7.3 years, 6 female) were compared with 69 age and gender matched (mean age 64.5 ± 8.7 years, 41 female) subjects with evidence of coronary artery disease and 140 controls with normal coronary arteries (mean age 58.6 ± 4.1 years, 81 female) in order to determine differences in inflammatory markers and cytokines, specific for CAE.In paper 4, we investigated long term follow up data of CAE patients without atherosclerotic burden. This represents follow up data of 66 patients with CAE, among 16,464 patients, who underwent diagnostic coronary angiography in Umea, Sweden and Letterkenny university Hospital, Ireland between 2003 and 2009. Of the 66 patients, long-term follow up (mean 11.3 ± 1.6 years) data was complete in 41 patients (age 66 ± 9 years), 12 Female. All hospital readmissions with Major Acute Cardiac Events (MACE) including mortality and morbidity and hospital readmissions for acute coronary syndrome (ACS) were compared with gender matched 41 controls. No subject had >20% coronary stenosis in any coronary branch. Results:Paper 1: The prevalence of CAE with acute MI was 2.7%. Apart from diabetes mellitus (DM) that was significantly less common in the CAE group (p=0.02), the other conventional cardiovascular risk factors were similar between ectatic and non-ectatic coronary arteries. The RCA and LCx were predominantly involved in patients with CAE (p=0.001 and 0.0001, respectively). CRP was higher (p=0.006) in CAE, but both WCC, neutrophil and neutrophil/lymphocyte ratio (N/L ratio) was lower (p = 0.002, 0.002 and 0.032). The short-term follow-up of 2 years showed no relationship between the inflammatory markers and MACE [(8/28, 28.6%) CAE vs. (13/60, 21.7%) without CAE, (p = 0.42)].Paper 2: We identified 65 different metabolites between CAE group and controls, 27 of them were identifiable using metabolomics library software (15 were fully identified and 12 were identified through the size of the side chains). Sixteen species of phosphatidylcholines (PC); and 11 sphyngomyelins (SM) species had significantly lower intensities in patients with CAE.Paper 3: Systemic levels of IFN-γ, TNF-α, IL-1β, IL-6 and IL-8 were significantly higher in the CAE group compared to the CAD group (p = 0.006, 0.001, 0.001, 0.046 and 0.009, respectively) and the control group (p = 0.032, 0.002, 0.001, 0.049 and 0.007 in the same order), while the levels of IL-2 and IL-4 were lower (P < 0.001 for both) compared to the CAD and the control group. No differences were detected in the systemic levels of cytokines IL-10, IL-12P “subunits IL-12 and IL-23”, and IL-13 between the two patient groupsPaper 4: While CAE patients were slightly older, they had longer follow up period (p<0.001) than controls. The overall mortality in the CAE group was higher (p<0.001) and similarly was CV mortality (p<0.03) compared with controls. MACE was similar in both groups (p=0.18). More patients smoked (p<0.001) and have family history for CAD (p<0.02) than controls but these variables were not different between survivals (36 patients) and non-survivors (5 patients). Females had more MACE than males (p<0.03). Finally, all non-survivors and 12/36 survivors had smoked and had dyslipidemia. Conclusion:Coronary artery ectasia, despite of common association with atherosclerosis, had a lower disease prevalence and dysregulated lipid metabolic profile than atherosclerosis. The pro-systemic inflammatory response in CAE is also different from atherosclerosis with different Cytokines milieu. In the context of CAE with acute coronary syndrome with obstructive atherosclerotic CAD, the management options should follow the standard guidelines for revascularization. CAE may lead to exaggerated inflammatory response in acute settings but the short-term outcome is similar to non-ectatic obstructive CAD. However, long term follow up data showed higher mortalities and hospital readmissions, yet no difference in MACE.
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| 2. |
- Calcutteea, Avin, 1978-
(författare)
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New insights in the assessment of right ventricular function : an echocardiographic study
- 2013
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: The right ventricle (RV) is multi-compartmental in orientation with a complex structural geometry. However, assessment of this part of the heart has remained an elusive clinical challenge. As a matter of fact, its importance has been underestimated in the past, especially its role as a determinant of cardiac symptoms, exercise capacity in chronic heart failure and survival in patients with valvular disease of the left heart. Evidence also exists that pulmonary hypertension (PH) affects primarily the right ventricular function. On the other hand, previous literature suggested that severe aortic stenosis (AS) affects left ventricular (LV) structure and function which partially recover after aortic valve replacement (AVR). However, the impact of that on RV global and segmental function remains undetermined. Objectives: We sought to gain more insight into the RV physiology using 3D technology, Speckle tracking as well as already applicable echocardiographic measures. Our first aim was to assess the normal differential function of the RV inflow tract (IT), apical and outflow tract (OT) compartments, also their interrelations and the response to pulmonary hypertension. We also investigated the extent of RV dysfunction in severe AS and its response to AVR. Lastly, we studied the extent of global and regional right ventricular dysfunction in patients with pulmonary hypertension of different aetiologies and normal LV function.Methods: The studies were performed on three different groups; (1) left sided heart failure with (Group 1) and without (Group 2) secondary pulmonary hypertension, (2) severe aortic stenosis and six months post AVR and (3) pulmonary hypertension of different aetiologies and normal left ventricular function. We used 3D, speckle tracking echocardiography and conventionally available Doppler echocardiographic transthoracic techniques including M-mode, 2D and myocardial tissue Doppler. All patients’ measurements were compared with healthy subjects (controls). Statistics were performed using a commercially available SPSS software.Results:1- Our RV 3D tripartite model was validated with 2D measures and eventually showed strong correlations between RV inflow diameter (2D) and end diastolic volume (3D) (r=0.69, p<0.001) and between tricuspid annular systolic excursion (TAPSE) and RV ejection fraction (3D) (r=0.71, p<0.001). In patients (group 1 & 2) we found that the apical ejection fraction (EF) was less than the inflow and outflow (controls: p<0.01 & p<0.01, Group 1: p<0.05 & p<0.01 and Group 2: p<0.05 & p<0.01, respectively). Ejection fraction (EF) was reduced in both patient groups (p<0.05 for all compartments). Whilst in controls, the inflow compartment reached the minimum volume 20 ms before the outflow and apex, in Group 2 it was virtually simultaneous. Both patient groups showed prolonged isovolumic contraction (IVC) and relaxation (IVR) times (p<0.05 for all). Also, in controls, the outflow tract was the only compartment where the rate of volume fall correlated with the time to peak RV ejection (r = 0.62, p = 0.03). In Group 1, this relationship was lost and became with the inflow compartment (r = 0.61, p = 0.01). In Group 2, the highest correlation was with the apex (r=0.60, p<0.05), but not with the outflow tract.2- In patients with severe aortic stenosis, time to peak RV ejection correlated with the basal cavity segment (r = 0.72, p<0.001) but not with the RVOT. The same pattern of disturbance remained after 6 months of AVR (r = 0.71, p<0.001). In contrast to the pre-operative and post-operative patients, time to RV peak ejection correlated with the time to peak outflow tract strain rate (r = 0.7, p<0.001), but not with basal cavity function. Finally in patients, RVOT strain rate (SR) did not change after AVR but basal cavity SR fell (p=0.04).3- In patients with pulmonary hypertension of different aetiologies and normal LV function, RV inflow and outflow tracts were dilated (p<0.001 for both). Furthermore, TAPSE (p<0.001), inflow velocities (p<0.001), basal and mid-cavity strain rate (SR) and longitudinal displacement (p<0.001 for all) were all reduced. The time to peak systolic SR at basal, mid-cavity (p<0.001 for both) and RVOT (p=0.007) was short as was that to peak displacement (p<0.001 for all). The time to peak pulmonary ejection correlated with time to peak SR at RVOT (r=0.7, p<0.001) in controls, but with that of the mid cavity in patients (r=0.71, p<0.001). Finally, pulmonary ejection acceleration (PAc) was faster (p=0.001) and RV filling time shorter in patients (p=0.03) with respect to controls.Conclusion: RV has distinct features for the inflow, apical and outflow tract compartments, with different extent of contribution to the overall systolic function. In PH, RV becomes one dyssynchronous compartment which itself may have perpetual effect on overall cardiac dysfunction. In addition, critical aortic stenosis results in RV configuration changes with the inflow tract, rather than outflow tract, determining peak ejection. This pattern of disturbance remains six month after valve replacement, which confirms that once RV physiology is disturbed it does not fully recover. The findings of this study suggest an organised RV remodelling which might explain the known limited exercise capacity in such patients. Furthermore, in patients with PH of different aetiologies and normal LV function, there is a similar pattern of RV disturbance. Therefore, we can conclude that early identification of such changes might help in identifying patients who need more aggressive therapy early on in the disease process.
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| 3. |
- Charisopoulou, Dafni, 1972-
(författare)
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Myocardial electromechanical function in long QT syndrome
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- AIM: The aim of this thesis is to assess, in LQTS and according to genotype, the myocardial electromechanical (EM) function response to exercise, its relation to symptoms and its response to b-blocker therapy. To achieve this aim, we conducted 4 studies with the following specific objectives: i. To study the ventricular repolarization (QTc interval) behaviour during stress and its potential haemodynamic effects, as reflected in left ventricular filling and stroke volume response to exercise.ii. To access the exercise response of electromechanical coupling, expressed by the electromechnical window (EMW), and its relation to symptoms.iii. To access for potential mechanical disturbances during stress by studying the myocardial contraction response to exercise, its effects on myocardial diastolic function and their relation to co-existent ventricular repolarization disturbances.iv. To investigate the myocardial behaviour during early relaxation an most particularly the longitudinal apico-basal relaxation sequence, its synamic response to exercise and any potentia contribution to the development of symptoms.v. To investigate the effect of b-blocker therapy on the above electromechanical parameters at rest and during exercise. METHODS: Forty seven (age 45±15yrs, 25 female, 20 symptomatic) LQTS mutation carriers and 35 healthy individuals (matched for age and sex) underwent an exercise test (Bruce protocol). ECG and doppler and speckle-tracking echo parameters were recorded at rest, peak exercise and recovery. RESULTS: We found that abnormal ventricular repolarization in LQTS carriers was related to marked LV mechanical dispersion and to abnormally reversed LV end-systolic electromechanical relationship and longitudinal early relaxation sequence. These phenomena worsened at peak exercise, especially in LQT1 carriers, and were related to impaired LV daistolic function and attenuated stroke volume response to exercise. Such abnormal electromechanical responses to exercise were more pronounces in LQTS subjects with previous adverse cardiac events and could better identigy these subjects than QTc interval alone. These disturbances were also less pronounced in LQTS carriers treated with b-blockers. CONCLUSION: Incorporating stress-echocardiograhic evaluation of electromechanical parameters in the routine assessment of LQTS individuals may help better stratification, symptom interpretation and management.
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| 4. |
- Ramzy Guirguis, Ihab, 1963-
(författare)
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Insights into the effect of myocardial revascularisation on electrical and mechanical cardiac function
- 2012
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Acute coronary syndrome is known for its effect on cardiac function and can lead to impaired segmental and even global myocardial function. Evidence exists that myocardial revascularisation whether pharmacological, interventional or surgical results in improvement of systolic and diastolic left ventricular (LV) function, particularly that of the long axis which represents the sub-endocardial function, known as the most sensitive layer to ischaemia. Objective: We sought to gain more insight into the early effect of pharmacological and interventional myocardial revascularisation on various aspects of cardiac function including endocrine, electrical, segmental, twist, right ventricular (RV) and left atrial (LA) function. In particular, we aimed to assess the response of ventricular electromechanical function to thrombolysis and its relationship with peptides levels. We also investigated the behaviour of RV function in the setting of LV inferior myocardial infarction (IMI) during the acute insult and early recovery. In addition, we aimed to assess in detail LA electrical and mechanical function in such patients. Finally, we studied the early effect of surgical revascularisation on the LV mechanics using the recent novel of speckle tracking echocardiography technology to assess rotation, twist and torsion and the strain deformation parameters as a tool of identifying global ventricular function. Methods: We used conventionally Doppler echocardiographic transthoracic techniques including M-mode, 2-Dimentional, myocardial tissue Doppler, and speckle tracking techniques. Commercially available SPSS as a software was used for statistical analysis. Results: 1-The elevated peptide levels at 7 days post-myocardial infarction correlated with the reduced mechanical activity of the adjacent non-infarcted segment thus making natriuretic peptides related to failure of compensatory hyperdynamic activity of the non-infarcted area rather than the injured myocardial segments. 2-RV segmental and global functions were impaired in acute IMI, and recovered in 87% of patients following thrombolysis. In the absence of clear evidence for RV infarction the disturbances in the remaining 13% may represent stunned myocardium with its known delayed recovery. 3-LA electromechanical function was impaired in acute inferior STEMI and improved after thrombolysis. The partial functional recovery suggests either reversible ischaemic pathology or a response to a non-compliant LV segment. The residual LA electromechanical and pump dysfunction suggest intrinsic pathology, likely to be ischaemic in origin. 4-LV function was maintained in a group of patients with multivessel coronary artery disease who underwent coronary artery bypass graft (CABG) surgery. Surgical myocardial revascularisation did not result in any early detectable change in the three functional components of the myocardium, including twist and torsion, as opposite to conventional percutaneous coronary intervention (PCI). Conclusion: The studied different materials in this thesis provide significant knowledge on various aspects of acute ischaemic cardiac pathology and early effect of revascularisation. The use of non-invasive imaging, particularly echocardiography with its different modalities, in studying such patients should offer immediate thorough bed-side assessment and assist in offering optimum management.
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| 5. |
- Shenouda, Rafik B., 1971-
(författare)
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Insight into Coro-Carotid atherosclerotic disease in patients with acute coronary syndrome
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: the arterial tree branches in different parts of human body are sharing the histological and physiological features. Atherosclerosis is a systemic arterial disease, hence is expected to affect to affect more than one arterial system with similar pathologic manifestations.Aim: the aim of this thesis is to highlight the relationship between the two arterial systems involved in common acute ischemia, the carotid and coronary arteries, and to focus on the diagnostic tools that could be of help in estabilishing accurate diagnosis.Methods: we conducted five studies, the first three looked into the acute coronary syndrome and the different echocardiographic imaging modalities, including 2-Dimentional wall motion abnormalities, M-mode measurments, and myocardial deformation parameters measurment (Strain and Strain rate) in identifying the culprit coronary lesion (study 1), early recovery of left ventricular function after acute coronary syndrome (study 2) and the third study is a comparison between conventional 2-D dobutamine stress echocardiography and dobutamine stress echocardiography analysis using speckle tracking technique. The fourth and fifth studies are analyzing the relationship between the carotid calcifications measured by conventional computed tomogaphy based on Agatston calcium scoring and that of the coronary arteries (study 4) and the fifth study looked at the carotid and coronary atherosclerosis manifestation in a systematic review and mata-analysis.Results: Left ventricular myocardial strain rate was the most sensetive peridictor of the culprit artery lesion in the setting of acute coronary syndrome, measurment of deformation parameters are more sensetive than those of conventional echo in detecting early recovery of left ventricular function after acute coronary syndrome. Myocardial deformation parameters messured by speckle traching technique during dobutamine stress echo cardiography are more senstive than convetional 2-D measurments in detecting the stenosed arteries. Coronary calcifications is 10 times higher than carotid calcifications in acute coronary syndrome patients. There was moderate relationship between Carotid intima media thickness and the degree of stenosis of the coronary arteries.Conclusions: resting echocardiographic measurments are accurate in predicting the culprit coronary artery lesions in patients presenting with acute coronary syndrome. myocardial deformation measurments are the most accurate parameter that identify culprit lesion and left venticular segmental recovery and also are more sensetive than conventioal 2-D dobutamine stress echo in redicting stenosed coronaries in patients post acute coronary syndrome and with low ejection fraction. atherosclerosis parameters of the carotid arteriescorrelates with those of the coronary circulation, despite different phenotypic presentation. this finding highlights the importance of measuring the carotid intima media thickness in suspected high risk patients with acute coronary syndrome.
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| 6. |
- Bytyci, Ibadete, 1983-
(författare)
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The important role of left atrial function parameters in clinical practice
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The aim of this thesis is to evaluate the role of left atrial function in clinical practice based on the following studies:1) Determining left atrial (LA) structure and myocardial function measurements that predict pulmonary capillary wedge pressure (PCWP).2) Identifying predictors of exercise capacity in patients with HFpEF and right ventricle (RV) dysfunction.3) Evaluating the relationship between LA stiffness (LASt) and cardiac events in HF patients with reduced to mid-range ejection fraction.4) Investigating the relationship between DM and LA remodelling in a group of patients with HF and reduced ejection fraction (HFrEF), and their combined impact on cardiac events. Study IMethods: This is a meta-analysis study. All electronic databases were searched up to December 2018 for studies on the relationship of LA diameter, LA volumes, peak atrial longitudinal strain (PALS), peak atrial contraction strain (PACS) and total emptying fraction (LAEF) with PCWP. Eighteen studies with 1343 patients were included. Summary sensitivity and specificity (with 95% CI) for evaluation of diagnostic accuracy and the best cut-off values for different LA indices in predicting raised PCWP were estimated using summary receiver operating characteristic analysis. Results: The pooled analysis showed association between PCWP and LA diameter: Cohen’s d = 0.87, LAVI max: d = 0.92 and LAVI min: d = 1.0 (p < 0001 for all). A stronger correlation was found between PCWP and PALS: d = 1.26, and PACS: d = 1.62, total EF d = 1.22 (p < 00001 for all). PALS ≤ 19% had a summary sensitivity of 80% (65 - 90) and summary specificity of 77% (52 - 92), and diagnostic odds ratio (DOR) > 15.1, whereas LAVI ≥ 34 ml/m2 had summary sensitivity of 75% (55 - 89) and summary specificity 77% (57 - 90), and DOR > 10.1 in predicting elevated PCWP. Conclusion: Compromised LA myocardial function and increased size predict raised cavity pressure. These results should assist in optimizing the follow-up clinical management of patients with fluctuating LA pressure. Study IIMethods: In 143 consecutive patients with HFpEF (age 62 ± 9 years, LV EF ≥45) and 41 controls, a complete echocardiographic study was performed. In addition to conventional measurements, LA compliance was calculated using the formula: [LAV max - LAV min/LAV min × 100]. Exercise capacity was assessed using the six-minute walking test (6-MWT). Tricuspid annular plane systolic excursion (TAPSE) < 1.7 cm was used to categorize patients with RV dysfunction (n = 40) from those with maintained RV function (n = 103).Results: Patients with RV dysfunction were older (p=0.002), had higher NYHA class (p= 0.001), higher LV mass index (p = 0.01), reduced septal and lateral MAPSE (p < 0.001 for all), enlarged LA (p = 0.001) impaired LA compliance index (p < 0.001) and exhibited a more compromised 6-MWT (p = 0.001). LA compliance index correlated more closely with 6-MWT (r = 0.51, p < 0.001) compared with the other LA indices (AP diameter, transverse diameter and volume indexed; r = -0.30, r = -0.35 and r = -0.38, respectively). In multivariate analysis, LA compliance index < 60% was 88% sensitive and 61% specific AUC = 0.80 (CI = 0.67 - 0.92; p = 0.001) in predicting exercise capacity.Conclusion: Impaired LA compliance was profound in patients with HFpEF and RV dysfunction and seems to be the most powerful independent predictor of limited exercise capacity. Study IIIMethods: This study included 215 consecutive ambulatory heart failure (HF) patients with ejection fraction (EF) < 50% (162 HF reduced EF (HFrEF) and 53 HF mid-range EF HFmrEF)) of mean age 66 ± 11 years and 24.4% were females. Peak LA strain (PALS) was measured by speckle tracking echocardiography and E/e' recorded from the apical four-chamber view. Non-invasive left atrial stiffness (LASt) was calculated using the equation: LASt = E/e' ratio/PALS. Documented cardiac events (CE) were HF hospitalization and cardiac death.Results: During a median follow up of 41 ± 34 months, 65 patients (30%) had CE. In multivariate analysis model, only raised LV filling pressure (E/e'), OR=2.292, (95% CI 2.099 to 2.859; p= 0.02), peak pulmonary artery pressure (PAP), OR = 1.050 (1.009 to 1.094; p= 0.01), PALS (OR = 0.932 (0.873 to 0.994; p = 0.02) and LASt OR = 3.781 (1.144 to 5.122; p = 0.001) independently predicted CE. LASt ≥ 0.76% was the most powerful predictor of CE, with 80% sensitivity, 73% specificity and AUC = 0.82, (CI = 0.73 to 0.87; p < 0.001) followed by PALS ≤ 16%, with 74% sensitivity, 72% specificity and AUC=0.77, (CI = 0.71 to 0.84; p < 0.001). These results were consistent irrespective of EF (p < 0.05). Conclusion: In a cohort of ambulatory HFrEF and HFmrEF patients, left atrial stiffness proved the most powerful predictor of clinical outcome. Study IVMethods. This study included 136 consecutive HFrEF patients (65 ± 11 years), 36 had DM and 86 had increased LA stiffness (LASt). All patients underwent complete conventional and tissue Doppler echocardiographic examinations and measurements were made including LA volumes and function. LASt was calculated using the formula: LASt = E/e’ratio / LA strain.Results. At 55 ± 37 months follow-up, free survival from CE was 69% in patients without DM and 44.4% in those with DM (p < 0.0001). The CE free-survival was lower in patients with increased LASt compared to normal LASt, (50 vs. 80%; p < 0.001), irrespective of the presence of DM (27 vs. 71%, p <0 .001). The best cut-off LASt value for predicting CE in the group as a whole was ≥ 0.82% [81% sensitivity, 72% specificity and AUC 0.82 (p < 0.001)]. LASt ≥ 0.82% also predicted CE in patients without DM [78% sensitivity, 71% specificity and AUC 0.80 (p < 0.001)] and was the strongest predictor in DM patients [85% sensitivity, 71% specificity and AUC = 0.847 (p < 0.001)].Conclusion. High LA stiffness is associated with poor clinical outcome in patients with heart failure and reduced ejection fraction. Diabetes has an additional incremental value in determining clinical outcome in those patients.
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| 7. |
- Ding, Wenhong, 1968-
(författare)
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Survival and functional recovery following valve replacement in patients with severe aortic stenosis
- 2013
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Aortic stenosis (AS) is the most common heart valve disease in Europe and North America. Age-related calcification of the valve is the commonest cause of acquired AS, especially in patients older than 70 years.Conventional surgical aortic valve replacement (SAVR) and the novel, minimally invasive transcatheter aortic valve implantation (TAVI), effectively preserve left ventricular (LV) function, relieve symptoms and improve survival in patients with severe symptomatic AS. However, patients with impaired LV function may carry significant operative risk, and long recovery time. In addition, such patients might have other comorbidities, and hence adding another challenge. Thus evaluation of ventricular function before and after AVR, as well as critical evaluation of TAVI patients should contribute to better clinical outcome.Methods: We studied LV function by conventional echocardiography before and after SAVR in the following groups; (I) 86 patients (aged 71±10 years) with severe AS and LV dysfunction; (II) 112 consecutive elderly AS patients (aged 77±2 years) and compared them with 72 younger patients (aged 60±1 years); (III)66 patients (age 70±2 years, 53 male) who underwent AVR for severe AS with concurrent LV dysfunction; (IV) 89 consecutive patients with symptomatic severeAS who underwent successful TAVI, 45 of whom received trans-apical TAVI (TA)(age 80.8±4.9 year, 26 male) and 44 trans-femoral TAVI (TF) (age 82.9±5.8 year,22 male).The conventional echocardiographic measurements were made according to the guidelines. Severe AS was identified by aortic valve mean pressure gradient >40mmHg or valve area <1.0 cm2. LV systolic dysfunction was identified as ejection fraction (EF) <50%. LV long-axis function was presented by mitral annular plane systolic excursion ( MAPSE ) at lateral wall and septal wall, which were measured from apical four-chamber view. Also from the same view, LV septal and lateral wall deformation using STE as well as global longitudinal systolic strain. The LV systolic twist as the net difference between apical rotation and basal rotation was measured from the parasternal apical and basal short-axis views in the TAVI patients.Results: Study I: In the low flow and high gradient group, operative (30-day) mortality was 10%, and peri-operative mortality was associated with lower mean LVEF, higher mitral E:A ratio, peak systolic pulmonary artery pressure (PSPAP), and higher serum creatinine (all p<0.001), NYHA class III–IV, concomitant coronary artery bypass graft (CABG), urgent surgery, and longer bypass-time (all p< 0.05). Mortality at 4 years was 17%. Univariate predictors of 4-year mortality were: lower EF (p<0.001), presence of restrictive LV filling (p<0.001), raised PSPAP (p<0.001) and CABG (p=0.037). However, only EF<40 % (p=0.03), the presence of restrictive LV filling (p=0.033) and raised PSPAP (p<0.01)independently predicted mortality in this group.Study II: Elderly patients had higher NYHA class, more frequent atrial fibrillation (AF), coronary artery disease (CAD), emergency operation and use of bioprosthetic valves. They also had shorter E-wave deceleration time (DT) and larger left atria (LA) (p<0.05 for all). 30-day mortality was 12% vs 4 % (Log Rank x2=3.02, p=0.08) and long term mortality was 18% vs 7% (Log Rank x2=4.38,p=0.04) in the two groups, respectively. Age was not related to mortality after adjustment for other variables. Among all variables, anemia (OR 4.20, CI:1.02–6.86, p=0.04), cardiopulmonary bypass (CPB) time (OR 1.02, CI 1.01–1.04,p<0.01), significant patient prosthesis mismatch (PPM) (OR 5.43, CI 1.04–18.40,p<0.05) were associated with 30-day mortality in elderly patients. Their long-term mortality was related to CBP time (OR 1.02, CI 1.00–1.05, p=0.04),PPM (OR 4.64, CI 1.33–16.11, p=0.02) and raised LA pressure: DT (OR 0.94, CI0.84–0.99, p=0.03) and pulmonary artery systolic pressure (PASP) (OR 1.12, CI1.03–1.19, p<0.001).STUDY III: Following SAVR peak aortic pressure gradient (AOPG) decreased and indexed valve area increased (64±3 to 19±1 mmHg and 0.30±0.01 to 0.89±0.03 cm2/m2, p<0.001 for both). LVEF increased (from 45±1 to 54±2%;p<0.001), LV end diastolic and end-systolic dimensions fell (LVEDD index: from 33±1 to 30±1 mm/m2; and LVESD index: from 27±1 to 20±1 mm/m2; (p<0.01 forboth). LV diastolic dysfunction improved as evidenced by the fall in E/A ratio (from 2.6±0.2 to 1.9±0.4) and prolongation of total filling time; (from 29.2±0.6 to31.4±0.5 s/min, p=0.01 for both). Among all echocardiographic variables, LV dimensions (LVEDD index, OR 0.70, CI 0.52–0.97, p<0.05; LVESD index, OR 0.57, CI 0.40–0.85, p=0.005) were the two independent predictors of post-operative LV functional recovery on multivariate analysis. A cut-off value ofpre-operative LVESD index<=27.5 mm/m2 was 85% sensitive and 72% specific inpredicting intermediate-term recovery of LV function after AVR (AUC, 0.72, p=0.002). STUDY IV: Before TAVI, there was no difference between the two patient groups in gender, age, body surface area (BSA) and baseline LV function. However, left ventricular mass index (LVMi), left atrial volume index (LAVi) and tricuspid regurgitation pressure drop (TRPdrop) were increased in the TA group (p<0.05).One week after TAVI, aortic pressure gradient (AOPG) markedly dropped in thetwo groups (both p<0.001), LVEDD index and LVESD index fell but EF andmyocardial strain remained unchanged. Overall cavity twist reduced (p<0.048).Significant LVESD index reduction was only seen in TF group (p=0.02) with a slight increase in LVEF (p=0.04). Lateral MAPSE increased only in the TF group(p=0.02). LV longitudinal systolic strain remained unchanged in TA patients while apical lateral strain increased in TF group. LV apical rotation fell in the two groups but basal rotation increased only in the TA patients (p=0.02). LAVi reduced in bothgroups and to a greater extent in TF TAVI (p=0.006), as did TRPdrop (p<0.001).Conclusion: SAVR and TAVI are two effective treatments for severe AS patients.The severity of pre-operative systolic and diastolic LV dysfunction is the major predictor of mortality following SAVR for low-flow and high gradient AS.Peri-operative AVR survival is encouraging in the elderly. Long term mortality in the elderly is related to PPM, LV diastolic dysfunction and secondary pulmonary hypertension. LV functional recovery was evident in most patients with LV dysfunction after SAVR. A lower prevalence of LV functional recovery in patients with large pre-operative LVESD index might signify the loss of contractile reserveand thus predict post-operative functional recovery. TAVI results in significant early improvement of segmental and overall ventricular function, particularly in patients receiving the trans-femoral approach. The delayed recovery of the trans-apical TAVI group, we studied, might reflect worse pre-procedural diastolic cavity function.
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- Sandström, Anette, 1966-
(författare)
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Long-term outcome and exercise capacity in adults with congenital heart disease with focus on tetralogy of Fallot
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Congenital heart disease (CHD) includes a wide range of malformations, from simple lesions, e.g. ventricular septal defect, that resolve spontaneously, to severe lesions, e.g. univentricular heart, not compatible with life without intervention. Tetralogy of Fallot (ToF) is the most common cyanotic congenital heart disease.In Sweden, approximately 1% of the children are born with CHD each year of which about 30 have ToF. The prognosis has improved remarkably due to advances in surgical techniques as well as peri- and postoperative care. Nowadays, 97% of babies with CHD born in Sweden can be expected to survive into adulthood. Despite huge improvements in prognosis, the relative mortality is still 7 to 97 times higher in patients with CHD, depending on lesion severity, compared with matched controls. Therefore, it is important to improve long-term follow-up and to identify robust and easily available tools to predict poor outcome and optimize timing of possible reinterventions. Addressing quality of life (QoL) has also become more important when survival increases.The main focus of this thesis was on QoL and long-term outcome in patients with repaired tetralogy of Fallot (rToF). In studies I, II and III, we analysed health related quality of life (HRQoL), prevalence of cardiac devices (i.e. pacemakers and implantable cardioverter defibrillators), and exercise capacity, respectively, in patients with rToF. In study IV, the aim was to broaden the perspective and include patients with a wide range of CHD, and to investigate whether exercise capacity, measured as workload could be of help in predicting mortality.Methods: The studies were performed as nationwide register studies. Data from the Swedish registry of congenital heart disease (SWEDCON) were used in studies I-IV. Study II also included data from the Swedish ICD and Pacemaker registry. In studies I-III, only patients with rToF were included, whilst study IV included patient with a broad spectrum of CHD diagnoses.Results: More than half (57%) of the patients with rToF reported best possible HRQoL. New York Heart Association (NYHA) class I and being physically active were associated with best possible HRQoL. Fourteen percent of patients with rToF had a cardiac device, either a pacemaker or an implantable cardioverter defibrillator (ICD). The prevalence of having a cardiac device was lower compared with reports from previous studies, especially for ICDs. Exercise capacity was 75% of predicted in patients with rToF and there was no decline in percent of predicted exercise capacity with age. Low heart rate reserve and low percent of predicted exercise capacity were associated with higher mortality.In study IV, including a wide range of lesions, percent of predicted exercise capacity was associated with mortality. Patients with percent of predicted exercise capacity between 50 and 69.9% had 1.7 times, and patients with exercise capacity <50% of predicted had 2.2 times higher risk of being deceased, over a median follow-up time of 9 years. NYHA class III-IV and ongoing cardiovascular medication were also associated with increased risk of death when adjusted for sex, physical activity and impaired left ventricular function.Conclusions: HRQoL in our patients with rToF was good, despite a fairly high prevalence of cardiac devices. Impaired exercise capacity was associated with an increased mortality. Our results reinforce the need for regular evaluation of exercise capacity in patients with CHD to identify patients at risk of worse outcome. Furthermore, the results in this thesis emphasize the importance of assessing NYHA class and physical activity as part of the follow-up since these parameters are easily attainable and strongly associated with HRQoL and exercise capacity.
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