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OBJECTIVES: This study evaluated the long-term risk of permanent pacemaker implantation following Cox-maze IV (CMIV) and concurrent mitral valve surgery.

METHODS: A retrospective, nationwide, registry-based analysis was conducted on postoperative permanent pacemaker implantation in 397 patients with symptomatic mitral valve insufficiency and atrial fibrillation who underwent CMIV and mitral valve surgery in Sweden between 2009 and 2017. They were compared to a registry group of 346 patients with atrial fibrillation who underwent mitral valve surgery without surgical ablation during 2014–2017. The follow-up ended on 30 September 2022.

RESULTS: CMIV patients were on average 4 years younger and had lower surgical risk than registry patients. More CMIV patients underwent early (<30 days) pacemaker implantation (13.3% vs. 5.5%, P = 0.002). CMIV patients had a doubled adjusted risk of requiring a pacemaker compared to registry patients after 8 years [HR 1.96, 95% CI 1.27–3.04]. In the CMIV group, 22% (95% CI 18–26%) had a pacemaker by 5 years, increasing to 27% (95% CI 22–31%) by 8 years, compared to 13% (95% CI 10–17%) at both time intervals in the registry group. Atrioventricular block II/III accounted for >60% of early pacemaker indications in both groups, and sinus node dysfunction was the indication for late pacemaker implantation in 48% in the CMIV group.

CONCLUSIONS: Patients undergoing CMIV concomitant with mitral valve surgery have a higher rate of postoperative pacemaker implantation compared to patients with atrial fibrillation undergoing mitral valve surgery alone. Sinus node dysfunction was the main indication for late pacemaker among CMIV patients.

Background and Aims: No-touch saphenous vein harvesting may enhance graft patency and improve clinical outcomes after coronary artery bypass grafting (CABG).

Methods: In this registry-based, randomized trial, patients undergoing CABG were randomly assigned to no-touch or conventional harvesting. The primary composite outcome was the proportion of patients with occluded/stenosed >50% vein graft on coronary computed tomography angiography, or who underwent percutaneous coronary intervention to a vein graft, or died. Secondary outcomes included clinical outcomes and leg wound complications.

Results: A total of 902 patients were enrolled with a mean total number of distal vein anastomoses of 2.0 (SD 0.87). The primary endpoint occurred in 90/454 (19.8%) of patients randomized to no-touch and in 107/446 (24.0%) of patients randomized to the conventional technique [difference, -4.3 percentage points; 95% confidence interval (CI) -10.1-1.6; P =. 15] at a mean follow-up time of 3.5 (SD 0.1) years. The composite of death, myocardial infarction, or repeat revascularization at 4.4 (SD 1.3) years occurred in 57/454 (12.6%) and 44/446 (9.9%) in the no-touch and conventional groups, respectively (hazard ratio 1.3; 95% CI, 0.87-1.93). Leg wound complications were more common in patients assigned to no-touch harvesting at 3 months [107/433 (24.7%) vs. 59/427 (13.8%); difference, 10.9 percentage points; 95% CI 5.7-16.1]. At 2 years, 189/381 (49.6%) vs. 91/361 (25.2%) had remaining leg symptoms (difference, 24.4 percentage points; 95% CI 17.7-31.1).

Conclusions: No-touch vein graft harvesting for CABG was not superior to conventional open harvesting in reducing vein graft failure or clinical events after CABG but increased leg wound complications. The primary outcome requires cautious interpretation due to a lower-than-expected number of primary events.

OBJECTIVES: Analysis of the long-term risks of ischaemic stroke and cerebral bleeding in patients with atrial fibrillation after mitral valve surgery and concomitant Cox-maze IV procedure.

METHODS: In total, 397 patients with symptomatic degenerative mitral valve insuffciency and atrial fibrillation, underwent mitral valve surgery and Cox-maze IV in Sweden between 2009 and 2017. In this retrospective nationwide analysis, patients were followed in national patient registers until 30 September 2022.

RESULTS: There were 4 deaths within 30 days (1.0%). Mean follow-up was 8.7 (0.1–13.4) years. Survival without ischaemic stroke or cerebral haemorrhage at 5 and 10 years were 90% and 74%, respectively. Nineteen patients experienced an ischaemic stroke, of which 4 were fatal. Five of 34 patients (14.7%) with a history of stroke preoperatively experienced ischaemic stroke during follow-up. The linearized rate of ischaemic stroke per patient-year was 0.6% and was similar regardless of left atrial appendage closure during surgery or whether a mechanical valve was inserted. The observed ischaemic stroke rate was lower than the predicted rate for all CHA₂DS₂-VASc score groups. Fourteen patients suffered cerebral bleeding, of which 3 were fatal. Patients who experienced cerebral bleeding were older and had higher mechanical valve implantation rate than those without cerebral bleeding.

CONCLUSIONS: Surgery for mitral valve insufficiency and concomitant Cox-maze IV can be performed with low perioperative risk. There is a low continuing risk of stroke long-term postoperatively that correlates with a higher CHA₂DS₂-VASc score. Patients with preoperative stroke are at increased risk of postoperative stroke despite atrial fibrillation surgery.

This paper analyzes data from coronary artery bypass grafting (CABG) using decision functions to represent rules. The data was collected at the University Hospital in Umeå, Sweden. The data contains pre-, intra-, and postoperative detail from 2975 heart operations during 1993-96. Each instance is represented by 14 preoperative variables, 4 intraoperative variables, and 9 postoperative variables. A logical method is used to predict the postoperative variables using preoperative variables. First, each postoperative variable is represented as a decision functions of preoperative variables. Then, for each postoperative variable, a minimal set of preoperative variables is derived. And finally, each postoperative variable is represented by a minimum set of rules using preoperative variables. With this method we can predict postoperative outcome, where prediction using preoperative data only is of particular interest e.g. for surgery scheduling.

Background: Animal and human data suggest that glutamate can enhance recovery of myocardial metabolism and function after ischemia. N-terminal pro-brain natriuretic peptide (NT-proBNP) reflects myocardial dysfunction after coronary artery bypass surgery (CABG). We investigated whether glutamate infusion can reduce rises of NT-proBNP in moderate- to high-risk patients after CABG.

Methods and findings: A prospective, randomized, double-blind study enrolled patients from November 15, 2015 to September 30, 2020, with a 30-day follow-up at 4 academic cardiac surgery centers in Sweden. Patients underwent CABG ± valve procedure and had left ventricular ejection fraction ≤0.30 or EuroSCORE II ≥3.0. Intravenous infusion of 0.125 M L-glutamic acid or saline at 1.65 mL/kg/h started 10 to 20 minutes before releasing the aortic cross-clamp, then continued for another 150 minutes. Patients, staff, and investigators were blinded to the treatment. The primary endpoint was the difference between preoperative and day-3 postoperative NT-proBNP levels. Analysis was intention to treat. We studied 303 patients (age 74 ± 7 years; females 26%, diabetes 47%), 148 receiving glutamate group and 155 controls. There was no significant difference in the primary endpoint associated with glutamate administration (5,390 ± 5,396 ng/L versus 6,452 ± 5,215 ng/L; p = 0.086). One patient died ≤30 days in the glutamate group compared to 6 controls (0.7% versus 3.9%; p = 0.12). No adverse events linked to glutamate were observed. A significant interaction between glutamate and diabetes was found (p = 0.03). Among patients without diabetes the primary endpoint (mean 4,503 ± 4,846 ng/L versus 6,824 ± 5,671 ng/L; p = 0.007), and the incidence of acute kidney injury (11% versus 29%; p = 0.005) was reduced in the glutamate group. These associations remained significant after adjusting for differences in baseline data. The main limitations of the study are: (i) it relies on a surrogate marker for heart failure; and (ii) the proportion of patients with diabetes had almost doubled compared to the cohort used for the sample size estimation.

Conclusions: Infusion of glutamate did not significantly reduce postoperative rises of NT-proBNP. Diverging results in patients with and without diabetes agree with previous observations and suggest that the concept of enhancing postischemic myocardial recovery with glutamate merits further evaluation.

OBJECTIVES: Our goal was to study long-term observed and relative survival after first-time aortic valve replacement surgery with or without concomitant coronary artery bypass surgery with reference to valve morphology (i.e. bicuspid vs tricuspid).

METHODS: Consecutive patients (n = 5086) from 3 Swedish hospitals, operated on between 1 January 2005 and 31 December 2016, were included. The 30-day mortality (n = 116, 2.3%) was excluded from the analysis of long-term observed and relative survival (n = 4970). Observed survival was analysed using Cox regression. Relative survival was calculated as the ratio between observed and expected survival based on data from the general Swedish population, matched for age, sex and calendar year. Risk factors for death were explored using multivariable analysis.

RESULTS: During the follow-up (median 4.7 years) period, 1157 (23%) patients died. Observed survival excluding 30-day mortality was 96.6%, 82.7% and 57.6% after 1, 5 and 10 years. Compared with the general Swedish population, the relative 1-, 5- and 10-year survival rates were 99.0%, 97.5% and 89.0%. Bicuspid morphology was independently associated with higher observed and relative long-term survival. Renal dysfunction, diabetes, chronic obstructive pulmonary disease, heart failure, smoking and atrial fibrillation were associated with higher long-term mortality. Combined surgery was not associated with higher observed or relative mortality.

CONCLUSIONS: Patients with a bicuspid morphology had better prognosis, matching that of the general population. With increased age, long-term relative survival compared favourably with survival in the general Swedish population. Adding coronary artery bypass surgery to an aortic valve replacement procedure did not affect long-term outcome.

Aims: High-sensitivity troponin T (hs-TnT) and high-sensitivity C reactive protein (hs-CRP) may convey prognostic information in patients with aortic stenosis (AS). This study evaluated if hs-TnT and hs-CRP associate with myocardial mass, and risk of future surgery for AS.

Methods: In total, 336 patients (48% women) with surgery for AS with previous participation in large population surveys were identified. Preoperatively, myocardial mass and the presence of coronary artery disease (CAD) were assessed. Two matched referents were allocated for each case, and hs-TnT and hs-CRP were determined in stored plasma from the baseline survey. Conditional logistic regression analysis was used to estimate the risk (OR (95% CI)) related to one (natural logarithm) SD increase in hs-TnT and hs-CRP. Kaplan-Mayer and Cox regression analyses were used to evaluate time to surgery.

Results: Median age (IQR) was 59.8 (10.3) years at survey, and median time between survey and surgery was 10.9 (9.3) years. Hs-TnT was independently associated with surgery for AS (1.24 (1.06–1.44)) irrespective of CAD, whereas Hs-CRP was not (1.05 (0.90–1.22)). Elevated hs-TnT levels at survey associated with shorter time to surgery (p<0.001), and with increased myocardial mass (p=0.002). Hs-CRP did not associate with time to surgery or with myocardial mass.

Conclusions: Hs-TnT—but not hs-CRP—was associated with increased risk of—and shorter time to—future surgery for AS. Hs-TnT associated with myocardial mass at surgery which indicates that hs-TnT could be a potential biomarker for determining intervention.

Background: Aortic stenosis (AS) is the most common valve disorder requiring surgery in developed countries. The etiology of AS is only partly known.  Identification of new biomarkers in prospective studies could lead to novel insights in the etiology of AS, and possibly lead to improved clinical management. Long term observed survival after aortic valve surgery has improved over the last decades despite an ageing population presenting with more comorbidities. Whether this is reflected in improved relative survival is not known. We evaluated if biomarkers associated prospectively with AS requiring surgery, and if these associations differed between genders, time to surgery and the presence of coronary artery disease (CAD). We also assessed long term observed and relative survival after aortic valve surgery with and without concomitant coronary artery by-pass surgery (CABG).

Methods and results: Study I: We prospectively studied the impact of lipoprotein (a)(Lp[a]) and apolipoproteins (Apo) in subgroups of AS. During a 20-year period, 336 patients with prior participation in large population-based surveys in northern Sweden were operated due to AS plus CABG when indicated. For each case two referents were matched. Data from the baseline survey were collected and included data on cardiovascular risk factors, health history, measurements of anthropometry, blood pressure, blood glucose and blood lipid levels were retrieved. Data from pre- and perioperative assessments were also collected. The presence of CAD was determined from the coronary angiogram. Elevated levels of Lp(a) and an elevated Apo B/Apo A 1 ratio were independently associated with future surgery for AS, but only in patients with concomitant CAD (OR 1.29, 95 % CI 1.07-1.55 and 1.43, 95 % CI 1.16-1.76 respectively). Study II: The same patient cohort as in study I was used. A panel of 92 cardiovascular candidate proteins were analysed with the multiplex proximity extension assay in samples obtained at baseline. Six circulating proteins (growth differentiation factor 15[GDF-15], galectin-4, von Willebrand factor [vWF], interleukin 17 receptor A, transferrin receptor protein 1, and proprotein convertase subtilisin/kexin type 9, [PCSK9]) were associated with future surgery for AS in patients with concurrent CAD (ORs ranged from 1.25 to 1.37 per SD increase in the protein signal). In the validation study with 106 additional cases, the association of all but one, (interleukin 17 receptor A), of these proteins were replicated in patients with AS and concurrent CAD but not in those without concurrent CAD. Study III: In the same patient cohort as in study I and II we evaluated if troponin T (TnT) and C-reactive protein (CRP) associated prospectively with future surgery for AS. TnT was independently associated with surgery for AS in patients both with (OR 1.22, 95 % CI 1.02-1.46) and without concomitant CAD (1.39, 95% CI 1.05-1.84). CRP was not associated with surgery for AS (OR 1.06, 95 % CI 0.92-1.23). Study IV: 4970 patients between 2005 and 2016 from three Swedish heart surgery centres, undergoing aortic valve replacement (AVR) due to either AS or aortic regurgitation in conjunction with CABG when indicated, were followed up. All-cause mortality, as well as both observed and relative survival, was analysed with focus on age, sex, type of valve prosthesis and the impact of concomitant CABG. Median follow-up was 4.7 years (2.3-7.6). 30-day mortality was 2.3 %. Long-term survival with 30-day mortality excluded was 96.6 %, 82.7 %, 57.6 % after 1, 5 and 10 years respectively. Relative survival rates (adjusting for the background mortality in the general Swedish population based on age, sex and year) were 99.6 %, 99.5 % and 90.6 % after 1, 5 and 10 years respectively. Age had a negative influence on observed survival (p<0.001) but was associated with better relative survival (relative mortality rate [RMR] 0.74, 95 % CI 0.71 - 0.77). Women had a lower observed mortality than men (p<0.001) but a lower relative survival (RMR 1.17, 95 % CI 1.02-1.35). Combined surgery (AVR+CABG) was not significantly associated with higher mortality (p=0.43) in a multivariable adjusted analysis. The presence of bicuspid morphology was associated with lower observed mortality compared with tricuspid valve, and a relative survival matching that in the general population.

Conclusion: I. Plasma levels of Lp(a) and the Apo B/Apo A 1 ratio were independently associated with future surgery for AS but only in patients with concomitant CAD. This finding suggests that patients with AS have different phenotypes and may open a new avenue of research on targeted risk factor interventions in this population. II. Five circulating proteins – GDF-15, galectin-4, vWF, transferrin receptor protein 1, and PCSK9 – were associated with the need for aortic valve surgery several years later. The role of these proteins should be investigated in future studies. III. Elevated plasma levels of TnT were independently associated with future surgery for AS, irrespective of the presence of concomitant CAD, which could indicate that the myocardium is subject to mechanical stress already in the subclinical stage of AS. This may be used as a clinical tool for identification of patients with subclinical AS who could benefit from early intervention. Elevated CRP levels did not associate with future AVR. IV. Relative survival following AVR was particularly good in the elderly matching that in the general population underlining the benefits of aortic valve surgery in properly selected patients. Women had decreased relative survival compared to men. This should be explored in future studies. Adding CABG to an AVR procedure was not associated with increased risk. Bicuspid valve morphology was associated with lower observed mortality compared with tricuspid valve morphology, and with a relative survival matching that of the general population.

Recently, a new approach was proposed to detect mild impairment in renal function: a reduced ratio between estimated glomerular filtration rate (eGFR) calculated by cystatin C and eGFR calculated by creatinine. We aimed to evaluate if this ratio is associated with aortic stenosis (AS) requiring surgery. We identified 336 patients that first participated in population surveys and later underwent surgery for AS (median age [interquartile range] 59.8 [10.3] years at survey and 68.3 [12.7] at surgery, 48% females). For each patient, two matched referents were allocated. Cystatin C and creatinine were determined in stored plasma. eGFR(cystatin C) and eGFR(creatinine) and their ratio were estimated. Conditional logistic regression analyses were used to estimate the risk (odds ratio (OR) with [95% confidence interval (CI)]) related to one (ln) standard deviation increase in the ratio between eGFR(cystatin C) and eGFR(creatinine). A high ratio was associated with lower risk for AS requiring surgery (OR [95% CI]) (OR 0.84 [0.73-0.97]), especially in women (0.74 [0.60-0.92] vs. 0.93 [0.76-1.13] in men). After further stratification for coronary artery disease (CAD), the association remained in women with CAD but not in women without CAD (0.60 [0.44-0.83] and 0.89 [0.65-1.23], respectively). In conclusion, a high ratio between eGFR(cystatin C) and eGFR(creatinine) was associated with lower risk for surgery for AS, especially in women. Mild impairment of renal function is thus associated with future risk for AS requiring surgery.