Anders Holmgren

Coronary artery bypass grafting-related bleeding complications in patients treated with ticagrelor or clopidogrel: a nationwide study

Abstract Aims Excessive bleeding impairs outcome after coronary artery bypass grafting (CABG). Current guidelines recommend withdrawal of clopidogrel and ticagrelor 5 days (120 h) before elective surgery. Shorter discontinuation would reduce the risk of thrombotic events and save hospital resources, but may increase the risk of bleeding. We investigated whether a shorter discontinuation time before surgery increased the incidence of CABG-related major bleeding complications and compared ticagrelor- and clopidogrel-treated patients. Methods and results All acute coronary syndrome patients in Sweden on dual antiplatelet therapy with aspirin and ticagrelor (n = 1266) or clopidogrel (n = 978) who underwent CABG during 2012–13 were included in a retrospective observational study. The incidence of major bleeding complications according to the Bleeding Academic Research Consortium-CABG definition was 38 and 31%, respectively, when ticagrelor/clopidogrel was discontinued <24 h before surgery. Within the ticagrelor group, there was no significant difference between discontinuation 72–120 or >120 h before surgery [odds ratio (OR) 0.93 (95% confidence interval, CI, 0.53–1.64), P = 0.80]. In contrast, clopidogrel-treated patients had a higher incidence when discontinued 72–120 vs. >120 h before surgery (OR 1.71 (95% CI 1.04–2.79), P = 0.033). The overall incidence of major bleeding complications was lower with ticagrelor [12.9 vs. 17.6%, adjusted OR 0.72 (95% CI 0.56–0.92), P = 0.012]. Conclusion The incidence of CABG-related major bleeding was high when ticagrelor/clopidogrel was discontinued <24 h before surgery. Discontinuation 3 days before surgery, as opposed to 5 days, did not increase the incidence of major bleeding complications with ticagrelor, but increased the risk with clopidogrel. The overall risk of major CABG-related bleeding complications was lower with ticagrelor than with clopidogrel.

Trans-catheter aortic valve implantation – early recovery of left and preservation of right ventricular function

This study aimed to assess the early effect of trans-catheter aortic valve implantation (TAVI) on right (RV) and left ventricular (LV) function in severe aortic stenosis (AS) patients. Twenty AS patients (age 79±6 years) were examined before, one week and six weeks after TAVI using Doppler echocardiography. LV ejection fraction (EF), long-axis [mitral annular plane systolic excursion (MAPSE)] and RV long-axis [tricuspid annular plane systolic excursion (TAPSE)] function, septal radial motion were studied. Results were compared with 30 AS patients before and one week after aortic valve replacement (AVR) as well as 30 normals (reference group). Before TAVI, LVEF was reduced and E/A was higher than the reference and AVR groups (P<0.05 for all). MAPSE, TAPSE and septal motion were equally reduced in TAVI and AVR patients (P<0.05 for all). One week after the TAVI, EF increased in patients with values <50% before the procedure. In contrast, AVR resulted in reversed septal motion (P<0.001) and depressed TAPSE (P<0.001). The extent of reversed septal motion correlated with that of TAPSE in the patients group as a whole after procedures (r=0.78, P<0.001). Six weeks after TAVI, RV function remained unchanged, but LVEF increased and E/A decreased (P<0.05 for both). Thus, TAVI procedure results in significant early improvement of LV systolic and diastolic function particularly in patients with reduced EF and preserves RV systolic function.

Aortic valve replacement normalizes left ventricular twist function

The aim of this study was to assess the effect of aortic valve replacement (AVR) on left ventricular (LV) twist function. We studied 28 severe aortic stenosis (AS) patients with normal LV ejection fraction (EF) before and six months after AVR. LV long axis function was assessed using M-mode and tissue Doppler and twist function using speckle tracking echocardiography. The data were compared with 28 age and sex-matched normal controls. In patients, LVEF remained unchanged after AVR. LV long axis function was reduced before surgery but normalized after AVR. LV twist was increased before (19.7 ± 5.7° vs. 12.9 ± 3.2°, P<0.001) and normalized after AVR (14.4 ± 5.2 °, P < 0.001). In normals, LV twist correlated with LV fractional shortening (r = 0.81, P<0.001) but not with EF. This relationship was reversed in patients before ( r= 0.52, P < 0.01) and after AVR (r = 0.34, P = ns). In patients with severe AS and normal EF, LV twist is exaggerated suggesting potential compensation for the reduced long axis function. These disturbances normalize within six months of AVR but lose their relationship with basal LV function.

Effect of pericardial repair after aortic valve replacement on septal and right ventricular function.

BACKGROUND Aortic valve replacement (AVR) is associated with reversed septal motion and right ventricular (RV) dysfunction but the cause remains uncertain. The aim of this study was to investigate the role of pericardial repair after AVR on septal and RV function. METHODS Thirty patients (62 ± 11 years, 18 males) with severe aortic stenosis were studied before and after AVR surgery using echocardiography. Patients were randomly allocated to pericardial repair vs. open pericardium. RV long axis displacement and outflow tract fractional shortening (fs) were measured. RV and right atrial (RA) tissue Doppler and strain rate (SR) were measured as well as RA area. Systolic interventricular septal motion towards and away from the RV was also determined. Stroke volume (SV) was measured by conventional Doppler method. Pre-operative data were compared with those from 30 normal gender and age matched controls. RESULTS Post-operatively, global RV ejection function was preserved as shown by SV. However, RV outflow tract fs and long axis displacement both fell (p<0.01) but not SR. RA area remained unchanged but RA SR fell (p<0.01). RV displacement correlated with the extent of reversed septal motion (r=0.60, p<0.001) as well as RA SR (r=0.54, p<0.001). None of the RV or septal measurements was affected by the pericardial repair procedure. CONCLUSION After AVR, septal motion is reversed and correlated directly with RV long axis function. The latter is not affected by pericardial repair but likely related to right atrial surgery injury.

Residual compromised myocardial contractile reserve after valve replacement for aortic stenosis

OBJECTIVE Despite recovery of left ventricular (LV) function and morphology after aortic valve replacement (AVR) for aortic stenosis (AS), its relationship with exercise capacity remains unknown. Twenty-one AVR patients (age 61 ± 12 years, 14 male) with normal ejection fraction (EF, 64 ± 7%) and 21 age- and sex-matched controls (57 ± 9 years, 10 male, EF 68 ± 8%) were studied. METHODS AND RESULTS All subjects performed semi-supine bicycle exercise and speckle tracking echocardiography (STE) study. Peak oxygen consumption (pVO(2)) was collected during semi-supine bicycle exercise. Systolic (GLSRs) and early diastolic (GLSRe) longitudinal strain rate using STE and Doppler echocardiographic parameters were measured at rest, submaximal, peak exercise, and 4 min after exercise. The two groups had comparable resting echocardiographic measurements. At peak exercise, pVO(2) was lower in patients than controls (18.5 ± 4.5 vs. 22.1 ± 4.3 L/min/kg, P < 0.05). GLSRs (0.98 ± 0.28 vs. 1.55 ± 0.30 1/s, P < 0.001), septal Sm (7.9 ± 1.4 vs. 11.1 ± 2.3 cm/s, P < 0.001) and their changes between rest and peak exercise (ΔGLSRs: 0.16 ± 0.33 vs. 0.68 ± 0.27 1/s, P < 0.001; ΔSm 2.29 ± 2.23 vs. 4.63 ± 2.29 cm/s, P < 0.01) were significantly lower in patients than controls. There was no correlation between pVO(2) and any echocardiographic measurements in controls. In patients, pVO(2) correlated with peak exercise GLSRs (r = 0.60, P = 0.0007), septal Sm (r = 0.65, P = 0.002), and Em (r = 0.57, P = 0.009). In a multivariate model, peak exercise GLSRs (β = 7.18, P = 0.03) was the only independent predictor of pVO(2) in the patients group. CONCLUSION Exercise capacity is subnormal after AVR for AS, irrespective of normal LVEF suggesting residual compromised myocardial functional reserve.

Perturbations in fatty acid metabolism and apoptosis are manifested in calcific coronary artery disease: An exploratory lipidomic study.

BACKGROUND Controversy exists concerning the beneficial or harmful effects of the presence of ectopic calcification in the coronary arteries. Additionally, further elucidation of the exact pathophysiological mechanism is needed. In this study, we sought to identify metabolic markers of vascular calcification that could assist in understanding the disease, monitoring its progress and generating hypotheses describing its pathophysiology. METHODS Untargeted lipid profiling and complementary modeling strategies were employed to compare serum samples from patients with different levels of calcific coronary artery disease (CCAD) based on their calcium score (CS). Subsequently, patients were divided into three groups: no calcification (NC; CS=0; n=26), mild calcification (MC; CS:1-250; n=27) and severe (SC; CS>250; n=17). RESULTS Phosphatidylcholine levels were found to be significantly altered in the disease states (p=0.001-0.04). Specifically, 18-carbon fatty acyl chain (FAC) phosphatidylcholines were detected in lower levels in the SC group, while 20:4 FAC lipid species were detected in higher concentrations. A statistical trend was observed with phosphatidylcholine lipids in the MC group, showing the same tendency as with the SC group. We also observed several sphingomyelin signals present at lower intensities in SC when compared with NC or MC groups (p=0.000001-0.01). CONCLUSIONS This is the first lipid profiling study reported in CCAD. Our data demonstrate dysregulations of phosphatidylcholine lipid species, which suggest perturbations in fatty acid elongation/desaturation. The altered levels of the 18-carbon and 20:4 FAC lipids may be indicative of disturbed inflammation homeostasis. The marked sphingomyelin dysregulation in SC is consistent with profound apoptosis as a potential mechanism of CCAD.

Can Myocardial Strain Differentiate Hypertrophic from Infiltrative Etiology of a Thickened Septum

Objectives: Radial systolic strain (ɛ) assessed by echocardiography has been shown to identify patterns of normal septal motion brought about by different layers, including left ventricular (LV) subendocardial (LV subendo) and mural (LV mural) layers. We aimed to use myocardial strain in assessing radial and longitudinal myocardial function in normal and thickened septum and to test if myocardial strain can differentiate hypertrophic from infiltrative cause of thickened septum. Methods: Forty‐five patients (age 61 ± 13 years, 22 males), 13 with hypertrophic cardiomyopathy, 15 with aortic stenosis, and 17 with familial amyloid polyneuropathy, were studied and compared with 29 controls (age 61 ± 12 years, 17 males) using 1D strain and conventional echocardiography. Results: Patients had normal LV ejection fraction and stroke volume but heart rate was higher (P < 0.05) compared to controls. Septal ɛ was reduced (–7.6 ± 7.0% vs. –14.0 ± 5.5%, for LV mural and –7.9 ± 14.7% vs. –20.3 ±–7.9% for LV subendo, P < 0.001 for both layers) across LV longitudinal axis but not along its radial axis. No difference was found in any of ɛ measurements between patient groups. A decrease in strain length by 50% increased the septal strain by more than 60% in both radial and longitudinal axes. Conclusion: Septal systolic strain measurements showed reduced longitudinal function but its localized nature failed to demonstrate radial disturbances in patients with pathologically thickened septum. No difference was found in systolic strain between patients according to the etiology of septal thickness. This limitation might be either technical or is explained by the maintained radial function in all patient groups. (Echocardiography 2011;28:408‐415)

Surgical stress induces acute coronary release of tissue‐type plasminogen activator in the pig

Background: Tissue‐type plasminogen activator (t‐PA) is an endothelium derived key enzyme in the initiation of endogenous fibrinolysis. Acute regulated release of active t‐PA occurs within minutes in response to threatening thrombotic vessel occlusion. The aim of this study was to investigate the impact of surgical stimulation on the kinetics of t‐PA release in the coronary vascular bed in the pig.

A Swedish consensus on the surgical treatment of concomitant atrial fibrillation

Abstract Atrial fibrillation (AF) is a common arrhythmia among patients scheduled for open heart surgery and is associated with increased morbidity and mortality. According to international guidelines, symptomatic and selected asymptomatic patients should be offered concomitant surgical AF ablation in conjunction with valvular or coronary surgery. The gold standard in AF surgery is the Cox Maze III (“cut-and-sew”) procedure, with surgical incisions in both atria according to a specified pattern, in order to prevent AF reentry circuits from developing. Over 90% of patients treated with the Cox Maze III procedure are free of AF after 1 year. Recent developments in ablation technology have introduced several energy sources capable of creating nonconducting atrial wall lesions. In addition, simplified lesion patterns have been suggested, but results with these techniques have been unsatisfactory. There is a clear need for standardization in AF surgery. The Swedish Arrhythmia Surgery Group, represented by surgeons from all Swedish units for cardiothoracic surgery, has therefore reached a consensus on surgical treatment of concomitant AF. This consensus emphasizes adherence to the lesion pattern in the Cox Maze III procedure and the use of biatrial lesions in nonparoxysmal AF.

Prolonged total isovolumic time is related to reduced long-axis functional recovery following valve replacement surgery for severe aortic stenosis.

BACKGROUND The left ventricular (LV) long axis (Lax) function is very sensitive in documenting myocardial abnormalities in aortic stenosis (AS). We hypothesized that Lax recovery after aortic valve replacement (AVR) is related to the extent of cavity dyssynchrony measured by total isovolumic time (t-IVT). METHODS A consecutive 107 patients (aged 70 ± 7 years, 70 male) with severe AS and Lax impairment were studied. T-IVT was measured before and after AVR. Reduced Lax function and its post-operative recovery were defined as mitral annular plane systolic excursion (MAPSE) ≦10 mm and an increase of MAPSE >10%, respectively. RESULTS LV function improved (EF: 43 ± 8 to 48 ± 10%; MAPSE: 7.9 ± 1.0 to 11.0 ± 2.4 mm) and t-IVT shortened (9.7 ± 3.7 to 7.0 ± 2.8s/min, p<0.01 for all) after AVR. Sixty-five (61%) patients had Lax recovery after a median of 32-month follow-up. Univariate predictors were LV size, LA dimensions, the presence of restrictive LV filling and prolonged t-IVT. Only LV end-systolic dimension, restrictive filling and t-IVT (OR 0.61, 95% CI 0.47-0.79, p<0.01) were independent predictors. A pre-operative t-IVT ≦ 9.3s/min was 81% sensitive and 63% specific in predicting Lax recovery (AUC 0.81, p<0.001). The prevalence of CAD or concomitant CABG were similar in 2 patient groups with different t-IVT. CONCLUSIONS Lax recovery was evident in the majority of AS patients after AVR. The lower prevalence of Lax recovery seen in patients with prolonged t-IVT suggests that dyssynchrony may play an important role in the process of adverse LV remodeling.