Publications by authors named "Markus Malmberg"

22 Publications

  • Page 1 of 1

Intravenous Interferon-β1a for the Treatment of Ischemia-Reperfusion Injury in Acute Myocardial Infarct in Pigs.

Heart Surg Forum 2021 Apr 27;24(2):E409-E413. Epub 2021 Apr 27.

Heart Center, Turku University Hospital and University of Turku, Turku, Finland.

Background: To investigate the potential of intravenously administered porcine recombinant interferon-β1a (IFN-β1a) for myocardial protection during acute ischemia-reperfusion (IR) injury in an experimental animal model.

Methods: Twenty-two piglets (mean ± standard deviation, 26.7 ± 1.65 kg) were assigned to either the IFN group (n = 12) or the control group (n = 10). IR injury was induced by occluding the distal left descending coronary artery for 30 minutes, with a reperfusion period of 6 h. In the IFN group, the animals received 12.5 µg IFN-β1a intravenously repeatedly; the control group received saline solution. The levels of interleukin-6 (IL-6) and cardiac troponin I (TnI) were measured, and the amount of myocardial damage was quantified by analyzing myocardial apoptosis and the mean fluorescence intensity (MFI) of methylene blue-stained cardiac tissue.

Results: In the IFN group, significantly more premature deaths occurred compared with the control group (25% versus 17%, P = .013). Between the groups, the mean heart rate was higher in the IFN group (102 ± 22 versus 80 ± 20 beats per minute, P = .02). IL-6 and TnI levels were comparable between the groups, with no significant difference, and there was no difference between the study groups in myocardial apoptosis in the infarcted myocardium. The percentage of MFI differed significantly between the IFN and control groups (90.75% ± 4.90% versus 96.02% ± 2.73%, P = .01).

Conclusion: In this acute IR injury animal model, IFN-β1a did not protect the myocardium from IR injury, but rather increased some of the unfavorable outcomes studied.
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http://dx.doi.org/10.1532/hsf.3639DOI Listing
April 2021

Late incidence and recurrence of new-onset atrial fibrillation after isolated surgical aortic valve replacement.

J Thorac Cardiovasc Surg 2021 Apr 9. Epub 2021 Apr 9.

Heart Center, Turku University Hospital and University of Turku, Turku, Finland; Division of Cardiovascular Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Mass. Electronic address:

Objectives: Atrial fibrillation (AF) is a common complication after cardiac surgery. More knowledge is needed about long-term AF recurrence and adverse outcomes related to new-onset AF (NOAF) during the index hospitalization.

Methods: A total of 1073 patients underwent isolated surgical aortic valve replacement at the 4 participating hospitals (2002-2014). After the exclusion of patients with a history of any preoperative AF, the final study population included 529 patients in the bioprosthetic and 253 patients in the mechanical valve prosthesis cohort. Median follow-up time was 5.4 (interquartile range, 3.4-8.2) years in the combined cohort.

Results: Altogether 333 (42.6%) patients had in-hospital NOAF and 250 (32.0%) AF after hospital discharge. In the mechanical cohort, 64 (25.3%) experienced in-hospital NOAF and 74 (29.2%) AF after hospital discharge, whereas in the bioprosthetic cohort, 269 (50.9%) patients had in-hospital NOAF and 176 (33.3%) AF after hospital discharge. Patients with NOAF during the index hospital stay had a multifold risk of AF after hospital discharge in the combined cohort (hazard ratio [HR], 3.68; 95% confidence interval [CI], 2.82-4.81; P < .0001) as well as in both cohorts separately (bioprosthetic: HR, 4.35; 95% CI, 3.05-6.22; P < .001; mechanical: HR, 2.54; 95% CI, 1.59-4.03; P < .001). Patients with an in-hospital NOAF also had a significantly higher adjusted risk of death during the follow-up in the mechanical (HR, 2.05; 95% CI, 1.10-3.82; P = .025) and bioprosthetic (HR, 1.63; 95% CI, 1.17-2.28; P = .004) valve prosthesis cohorts.

Conclusions: NOAF during the index hospitalization is associated with a 2- to 4-fold risk of later AF and 1.6- to 2.0-fold risk of all-cause mortality after mechanical and bioprosthetic surgical aortic valve replacement.
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http://dx.doi.org/10.1016/j.jtcvs.2021.03.101DOI Listing
April 2021

Infective endocarditis and outcomes of mitral valve replacement.

Eur J Clin Invest 2021 May 1:e13577. Epub 2021 May 1.

Heart Center, Turku University Hospital and University of Turku, Turku, Finland.

Background: We investigated the long-term outcomes of mitral valve replacement (MVR) in native mitral valve infective endocarditis (IE).

Methods: Multicentre, population-based cohort register study consisted of 1233 consecutive adult patients treated with first-time MVR in Finland. Mitral valve IE was diagnosed in 170 of these patients. Propensity score matching resulted in 134 pairs with balanced baseline characteristics. The median follow-up was 6.1 years.

Results: Pre-operative native mitral valve IE was associated with an increased hazard of 10-year mortality (38.8% vs 30.5%; HR 2.13; CI 1.17-3.85; P = .013) after MVR. Occurrence of major bleeding was higher in IE patients (26.0%) vs non-IE patients (23.4%) during the 10-year follow-up (HR 2.80; CI 1.01-7.77; P = .048). Hospital admission duration after MVR was longer in IE patients (median 28 vs 11 days; P < .0001). Cumulative ischaemic stroke rate was similar between patient groups (12.1% in IE vs 15.1% in non-IE; P = .493). Re-sternotomy was performed in 13.4% of IE patients and 9.0% of non-IE patients (P = .261).

Conclusions: Patients with native mitral valve IE have a higher risk of death and major bleeding after MVR than matched patients without IE. Results highlight the importance of complication prevention in these patients.
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http://dx.doi.org/10.1111/eci.13577DOI Listing
May 2021

A randomized prospective multicenter trial for stroke prevention by prophylactic surgical closure of the left atrial appendage in patients undergoing bioprosthetic aortic valve surgery--LAA-CLOSURE trial protocol.

Am Heart J 2021 Jul 30;237:127-134. Epub 2021 Mar 30.

St. Antonius Ziekenhuis, Nieuwegein, the Netherlands.

Patients undergoing surgical aortic valve replacement (SAVR) are at high risk for atrial fibrillation (AF) and stroke after surgery. There is an unmet clinical need to improve stroke prevention in this patient population. The LAA-CLOSURE trial aims to assess the efficacy and safety of prophylactic surgical closure of the left atrial appendage for stroke and cardiovascular death prevention in patients undergoing bioprosthetic SAVR. This randomized, open-label, prospective multicenter trial will enroll 1,040 patients at 13 European sites. The primary endpoint is a composite of cardiovascular mortality, stroke and systemic embolism at 5 years. Secondary endpoints include cardiovascular mortality, stroke, systemic embolism, bleed fulfilling academic research consortium (BARC) criteria, hospitalization for decompensated heart failure and health economic evaluation. Sample size is based on 30% risk reduction in time to event analysis of primary endpoint. Prespecified reports include 30-day safety analysis focusing on AF occurrence and short-term outcomes and interim analyses at 1 and 3 years for primary and secondary outcomes. Additionally, substudies will be performed on the completeness of the closure using transesophageal echocardiography/cardiac computed tomography and long-term ECG recording at one year after the operation.
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http://dx.doi.org/10.1016/j.ahj.2021.03.014DOI Listing
July 2021

Patients with rheumatoid arthritis have impaired long-term outcomes after myocardial infarction - a nationwide case-control registry study.

Rheumatology (Oxford) 2021 Mar 1. Epub 2021 Mar 1.

Heart Center, Turku University Hospital and University of Turku, Turku, Finland.

Objective: To investigate the long-term outcomes of patients with rheumatoid arthritis (RA) after myocardial infarction (MI).

Methods: All-comer, real-life MI patients with RA (n = 1614, mean age 74 years) were retrospectively compared to propensity score (1:5) matched MI patients without RA (n = 8070) in a multicenter, nationwide, cohort register study in Finland. The impact of RA duration and the usage of corticosteroids and antirheumatic drugs on RA patients' outcomes were also studied. The median follow-up was 7.3 years.

Results: RA was associated with an increased 14-year mortality risk after MI compared to patients without RA (80.4% vs. 72.3%; HR 1.25; CI 1.16-1.35; p < 0.0001). Patients with RA were at higher risk of new MI (HR 1.22; CI 1.09-1.36; p = 0.0001) and revascularisation (HR 1.28; CI 1.10-1.49; p = 0.002) after discharge from index MI. Cumulative stroke rate after MI did not differ between RA and non-RA patients (p = 0.322). RA duration and corticosteroid usage before MI, but not use of methotrexate or biologic antirheumatic drugs, were independently associated with higher mortality (p < 0.001) and new MI (p = 0.009). A higher dosage of corticosteroids prior to MI was independently associated with higher long-term mortality (p = 0.002) and methotrexate usage with lower stroke rate (p = 0.034). Serological status of RA was not associated with outcomes.

Conclusion: RA is independently associated with poorer prognosis after MI. RA duration and corticosteroid usage and dosage were independent predictors of mortality after MI in RA. Special attention is needed for improvement of outcomes after MI in this vulnerable population.
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http://dx.doi.org/10.1093/rheumatology/keab204DOI Listing
March 2021

Dedicated plug based closure for large bore access -The MARVEL prospective registry.

Catheter Cardiovasc Interv 2021 May 21;97(6):1270-1278. Epub 2020 Dec 21.

Department of Cardiology, Erasmus University Medical Center, Rotterdam, The Netherlands.

Objectives: To study safety and performance of the MANTA Vascular closure device (VCD) under real world conditions in 10 centers.

Background: The MANTA is a novel plug-based device for large bore arteriotomy closure.

Methods: We included all eligible patients who underwent transfemoral large bore percutaneous procedures. Exclusion criteria were per operator's discretion and included severe calcification or marked tortuosity of the access vessel, presence of marked obesity/cachexia or a systolic blood pressure above 180 mmHg. The primary performance endpoint was time to hemostasis. Primary and secondary safety endpoints were major and minor access site related vascular complications up to 30 days, respectively. Vascular complications were adjudicated by an independent clinical event committee according to VARC-2 criteria. We performed multivariable logistic regression to estimate the effect of baseline and procedural characteristics on any and major vascular complications.

Results: Between February 2018 and July 2019 500 patients were enrolled undergoing Transcatheter aortic valve replacement (TAVR, N = 496), Balloon aortic valvuloplasty (BAV, N = 2), Mechanical circulatory support (MCS, N = 1) or Endovascular aneurysm repair (EVAR, N = 1). Mean age was 80.8 ± 6.6 years with a median STS-score of 2.7 [IQR 2.0-4.3] %. MANTA access site complications were major in 20 (4%) and minor in 28 patients (5.6%). Median time to hemostasis was 50 [IQR 20-120] sec. Severe femoral artery calcification, scar presence in groin, longer procedure duration, female gender and history of hypertension were independent predictors for vascular complications.

Conclusion: In this study, MANTA appeared to be a safe and effective device for large bore access closure under real-world conditions.
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http://dx.doi.org/10.1002/ccd.29439DOI Listing
May 2021

Surgical aortic valve replacement and infective endocarditis.

Eur J Clin Invest 2021 Jun 23;51(6):e13476. Epub 2020 Dec 23.

Heart Center, Turku University Hospital and University of Turku, Turku, Finland.

Background: We wanted to investigate the influence of native-valve infective endocarditis (IE) on long-term outcomes of surgical aortic valve replacement (SAVR).

Methods: Native-valve patients with IE (n = 191) were compared to propensity score-matched patients without IE (n = 191), all treated with SAVR, in a multicentre, population-based cohort register study in Finland. The median follow-up was 6.2 years.

Results: Infective endocarditis as the indication for SAVR was associated with an increased hazard of 10-year mortality (37.1% vs 24.2%; HR 1.83; CI 1.03-3.26; P = .039). Ischaemic stroke was also more frequent in IE patients during 10-year follow-up (15.8% vs 7.5%; HR 3.80; CI 1.42-10.18; P = .008). Major bleeding within first year after SAVR was more frequent in patients with IE (7.0% vs 2.9%; P = .038). Ten-year major bleeding rate was 32.4% in IE vs 24.5% in non-IE groups (P = .174). Aortic valve re-operation rate was 4.3% in IE vs 8.4% in non-IE groups (P = .975). Admission duration after SAVR was longer in IE (median 29 vs 9 days; P < .0001). There was no difference in 30-day mortality after SAVR.

Conclusions: Patients with native-valve IE have a higher risk of death, ischaemic stroke, and early major bleeding after SAVR than matched patients without IE. Results confirm the high risk for complications of IE patients after SAVR and highlight the importance of vigorous prevention of both stroke and bleeding after SAVR in these patients.
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http://dx.doi.org/10.1111/eci.13476DOI Listing
June 2021

Outcome of acute myocardial infarction versus stable coronary artery disease patients treated with coronary bypass surgery.

Ann Med 2021 12 14;53(1):70-77. Epub 2020 Sep 14.

Center for Population Health Research, Turku University Hospital and University of Turku, Turku, Finland.

Objective: To study the long-term outcome differences between acute myocardial infarction (MI) and stable coronary artery disease (CAD) patients treated with coronary artery bypass grafting (CABG).

Methods: We studied retrospectively patients with MI ( = 1882) or stable CAD ( = 13117) treated with isolated CABG between 2004 and 2014. Inverse propensity probability weight adjustment for baseline features was used. Median follow-up was 7.9 years.

Results: In-hospital mortality (8.6% vs. 1.6%; OR 5.94;  < .0001) and re-sternotomy (5.5% vs. 2.7%; OR 2.07;  < .0001) were more common in MI patients compared to stable CAD patients. Hospital surviving MI patients had higher all-cause mortality (28.2% vs. 22.2%; HR 1.37;  = .002) and MACE rate (34.4% vs. 27.4%; HR 1.22; CI 1.00-1.50;  = .049) at 10-year follow-up. Cardiovascular mortality (15.9% vs. 12.7%; HR 1.36;  = .017) and rate of new myocardial infarction (12.0% vs. 9.8%; HR 1.40;  = .034) were also higher in MI patients during follow-up. In follow-up of stabilized first-year survivors, the difference in all-cause (26.5% vs. 20.7%; HR 1.40;  = .003) and cardiovascular (14.2% vs. 11.4%; HR 1.37;  = .027) mortality continued to increase between MI and stable CAD patients.

Conclusion: MI patients have poorer short- and long-term outcomes compared to stable CAD patients after CABG and risk difference continues to increase with time. Key Messages Patients with myocardial infarction have poorer short- and long-term outcomes compared to stable coronary artery disease patients after coronary artery bypass grafting (CABG). Higher risk of death continues also in stabilized first-year myocardial infarct survivors. The importance of efficient secondary prevention and follow-up highlights in post-myocardial infarct population after CABG.
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http://dx.doi.org/10.1080/07853890.2020.1818118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7877950PMC
December 2021

Outcomes After ST-Segment Versus Non-ST-Segment Elevation Myocardial Infarction Revascularized by Coronary Artery Bypass Grafting.

Am J Cardiol 2020 11 29;135:17-23. Epub 2020 Aug 29.

Heart Center, Turku University Hospital and University of Turku, Turku, Finland; Research Center of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland; Center for Population Health Research, Turku University Hospital and University of Turku, Turku, Finland; Administative Center, Hospital District of Southwest Finland, Turku, Finland.

The objectives of this study were to investigate the outcome differences between ST-segment elevation myocardial infarction (STEMI) and non-ST-segment elevation myocardial infarction (NSTEMI) patients treated with coronary artery bypass grafting surgery (CABG). We conducted a multicenter, retrospective cohort follow-up study of consecutive patients with STEMI (surgery ≤48 hours of admission; n = 348) or NSTEMI (n = 1,160) revascularized with first-time isolated CABG in Finland using nationwide registries (median age 68 years, 24% women). The short- and long-term (10-year) outcomes were studied with inverse propensity probability weight adjustment for baseline features. The median follow-up was 5.2 years. In-hospital mortality (11.4% vs 5.3%; adj. odds ratio [OR] 2.27; confidence interval [CI] 1.41 to 3.66; p = 0.001) and re-sternotomy rates (6.9% vs 3.5%; adj. OR 2.07; CI 1.22 to 3.51; p = 0.007) were higher in STEMI patients. Long-term all-cause mortality did not differ between STEMI and NSTEMI patients among all operated patients (30.2% vs 28.3%; adj. HR 1.30; CI 0.97 to 1.75; p = 0.080) or hospital survivors (21.6 vs 24.3%; HR 0.93; CI 0.64 to 1.36; p = 0.713). Occurrence of major adverse cardiovascular event in hospital survivors within 10 years was 34.7% in STEMI versus 29.6% in NSTEMI (adj. HR 1.24; CI 0.88 to 1.76; p = 0.220). Occurrences of cardiovascular death (14.6% vs 14.4%; p = 0.773), myocardial infarction (MI; 15.2% vs 10.3%; p = 0.203), and stroke (10.8% vs 14.8%; p = 0.242) were also comparable. In conclusion, patients with STEMI have poorer short-term outcome compared to NSTEMI patients after revascularization by CABG, but the long-term outcomes are comparable regardless of MI type. Thus, both short- and long-term risks should be considered when evaluating patient´s for CABG eligibility by MI type.
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http://dx.doi.org/10.1016/j.amjcard.2020.08.042DOI Listing
November 2020

Indications and predictors for pacemaker implantation after isolated aortic valve replacement with bioprostheses: the CAREAVR study.

Interact Cardiovasc Thorac Surg 2020 09;31(3):398-404

Heart Center, Turku University Hospital and University of Turku, Turku, Finland.

Objectives: We sought to study the indications, long-term occurrence, and predictors of permanent pacemaker implantation (PPI) after isolated surgical aortic valve replacement with bioprostheses.

Methods: The CAREAVR study included 704 patients (385 females, 54.7%) without a preoperative PPI (mean ± standard deviation age 75 ± 7 years) undergoing isolated surgical aortic valve replacement at 4 Finnish hospitals between 2002 and 2014. Data were extracted from electronic patient records.

Results: The follow-up was median 4.7 years (range 1 day to 12.3 years). Altogether 56 patients received PPI postoperatively, with the median 507 days from the operation (range 6 days to 10.0 years). The PPI indications were atrioventricular block (31 patients, 55%) and sick sinus syndrome (21 patients, 37.5%). For 4 patients, the PPI indication remained unknown. A competing risks regression analysis (Fine-Gray method), adjusted with age, sex, diabetes, coronary artery disease, preoperative atrial fibrillation (AF), left ventricular ejection fraction, New York Heart Association class, AF at discharge and urgency of operation, was used to assess risk factors for PPI. Only AF at discharge (subdistribution hazard ratio 4.34, 95% confidence interval 2.34-8.03) was a predictor for a PPI.

Conclusions: Though atrioventricular block is the major indication for PPI after surgical aortic valve replacement, >30% of PPIs are implanted due to sick sinus syndrome during both short-term follow-up and long-term follow-up. Postoperative AF versus sinus rhythm conveys >4-fold risk of PPI.

Clinical Trial Registration: clinicaltrials.gov Identifier: NCT02626871.
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http://dx.doi.org/10.1093/icvts/ivaa119DOI Listing
September 2020

Adverse events and survival with postpericardiotomy syndrome after surgical aortic valve replacement.

J Thorac Cardiovasc Surg 2020 Dec 28;160(6):1446-1456. Epub 2020 Jan 28.

Heart Center, Turku University Hospital and University of Turku, Turku, Finland; Division of Cardiovascular Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Mass.

Objectives: Postpericardiotomy syndrome (PPS) is a relatively common complication after cardiac surgery. However, long-term follow-up data on the adverse events and mortality of PPS patients requiring invasive interventions are scarce.

Methods: We sought to assess the occurrence of mortality, new-onset atrial fibrillation (AF), cerebrovascular events, and major bleeds in PPS patients requiring medical attention in a combination database of 671 patients who underwent isolated surgical aortic valve replacement with a bioprosthesis (n = 361) or mechanical prosthesis (n = 310) between 2002 and 2014 (Cardiovascular Research Consortium-A Prospective Project to Identify Biomarkers of Morbidity and Mortality in Cardiovascular Interventional Patients [CAREBANK] 2016-2018). PPS was defined as moderate if it resulted in delayed hospital discharge, readmission, or medical therapy because of the symptoms; and severe if it required interventions for the evacuation of pleural or pericardial effusion.

Results: The overall incidence of PPS was 11.2%. Median time to diagnosis was 16 (interquartile range, 11-36) days. Severe PPS was diagnosed in 3.6% of patients. Severe PPS seemed to be associated with higher mortality (hazard ratio, 2.01; 95% confidence interval, 1.03-3.91; P = .040). Moderate or severe PPS increased the risk of new-onset AF during the early postoperative period (hazard ratio, 1.72; 95% confidence interval, 1.12-2.63; P = .012). No significant associations were found between PPS and cerebrovascular events or major bleeds during the follow-up.

Conclusions: Patients with PPS requiring invasive interventions are at increased risk for mortality unlike those with mild to moderate forms of the disease. PPS requiring medical attention is associated with a higher AF rate during the early postoperative period but has no significant effect on the occurrence of major stroke, stroke or transient ischemic attack, or major bleeds during long-term follow-up.
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http://dx.doi.org/10.1016/j.jtcvs.2019.12.114DOI Listing
December 2020

Preoperative paroxysmal atrial fibrillation predicts high cardiovascular mortality in patients undergoing surgical aortic valve replacement with a bioprosthesis: CAREAVR study.

Clin Cardiol 2020 Apr 5;43(4):401-409. Epub 2020 Feb 5.

Heart Center, Kuopio University Hospital and University of Eastern Finland, Kuopio, Finland.

Background: Preoperative permanent atrial fibrillation (AF) is associated with impaired outcome after surgical aortic valve replacement (SAVR). The impact of preoperative paroxysmal AF, however, has remained elusive.

Purpose: We assessed the impact of preoperative paroxysmal AF on outcome in patients undergoing SAVR with bioprosthesis.

Methods: A total of 666 patients undergoing isolated AVR with a bioprosthesis were included. Survival data was obtained from the national registry Statistics Finland. Patients were divided into three groups according to the preoperative rhythm: sinus rhythm (n = 502), paroxysmal AF (n = 90), and permanent AF (n = 74).

Results: Patients in the sinus rhythm and paroxysmal AF groups did not differ with respect to age (P = .484), gender (P = .402) or CHA DS -VASc score (P = .333). At 12-month follow-up, AF was present in 6.2% of sinus rhythm patients and in 42.4% of paroxysmal AF patients (P < .001). During follow-up, incidence of fatal strokes in the paroxysmal AF group was higher compared to sinus rhythm group (1.9 vs 0.4 per 100 patient-years, HR 4.4 95% Cl 1.8-11.0, P = .001). Cardiovascular mortality was higher in the paroxysmal AF group than in the sinus rhythm group (5.0 vs 3.0 per 100 patient-years, HR 1.70 95% CI 1.05-2.76, P = .03) and equal to patients in the permanent AF (5.0 per 100 patient-years).

Conclusion: Patients undergoing SAVR with bioprosthesis and history of paroxysmal AF had higher risk of developing permanent AF, cardiovascular mortality and incidence of fatal strokes compared to patients with preoperative sinus rhythm. Life-long anticoagulation should be considered in patients with a history of preoperative paroxysmal AF.
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http://dx.doi.org/10.1002/clc.23329DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7144481PMC
April 2020

Comparison of Long-Term Outcomes of Patients Having Surgical Aortic Valve Replacement With Versus Without Simultaneous Coronary Artery Bypass Grafting.

Am J Cardiol 2020 03 28;125(6):964-969. Epub 2019 Dec 28.

Heart Center, Turku University Hospital and University of Turku, Turku, Finland; Research Center of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland; Center for Population Health Research, Turku University Hospital and University of Turku, Turku, Finland; Administative Center, Hospital District of Southwest Finland, Turku, Finland. Electronic address:

Coronary artery disease is a common co-morbidity of aortic stenosis. When needed, adding coronary artery bypass grafting (CABG) to surgical aortic valve replacement (SAVR) is the standard treatment method, but the impact of concomitant CABG on long-term outcomes is uncertain. We compared long-term outcomes of SAVR patients with and without CABG. Hospital survivors aged ≥50 years discharged after SAVR ± CABG in Finland between 2004 and 2014 (n = 6,870) were retrospectively studied using nationwide registries. Propensity score matching (1:1) was used to identify patients with comparable baseline features (n = 2,188 patient pairs, mean age 73 years). The end points were postoperative 10-year major adverse cardiovascular outcome (MACE), all-cause mortality, stroke, major bleeding, and myocardial infarction. Median follow-up was 6 years. Cumulative MACE rate (39.5% vs 35.6%; hazard ratio [HR] 1.04; p = 0.677) and mortality (32.7% vs 31.0%; HR 1.03; p = 0.729) after SAVR were comparable with or without CABG. Myocardial infarction was more common in patients with CABG (13.4% vs 6.9%; HR 1.47; p = 0.0495). Occurrence of stroke (15.1% vs 13.5%; p = 0.998) and major bleeding (20.0% vs 21.9%; p = 0.569) were comparable. There was no difference in gastrointestinal (8.1% vs 10.3%; p = 0.978) or intracranial bleeds (6.0% vs 5.5%; p = 0.794). The use of internal mammary artery in CABG did not have an impact on the results. In conclusion, matched patients with and without concomitant CABG had comparable long-term MACE, mortality, stroke, and major bleeding rates after SAVR. In conclusion, our results indicate that need for concomitant CABG has limited impact on long-term outcomes after initially successful SAVR.
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http://dx.doi.org/10.1016/j.amjcard.2019.12.015DOI Listing
March 2020

Performance of CHADS-VASc score for stroke prediction after surgical aortic valve replacement.

J Thorac Cardiovasc Surg 2019 Mar 29;157(3):896-904. Epub 2018 Jul 29.

Heart Center, Turku University Hospital and University of Turku, Turku, Finland; Department of Surgery, Oulu University Hospital, Oulu, Finland.

Objective: Stroke is a frequent complication occurring early and late after surgical aortic valve replacement. There is an unmet clinical need for simple tools to assess postoperative stroke risk. We sought to assess the predictive performance of Congestive heart failure; Hypertension; Age ≥75 (doubled); Diabetes mellitus; prior Stroke, transient ischemic attack or thromboembolism (doubled); Vascular disease; Age 65 to 74; Sex category (female) (CHADS-VASc) score in patients undergoing surgical aortic valve replacement with a bioprosthesis.

Methods: Seven hundred fourteen patients undergoing isolated surgical aortic valve replacement with a bioprosthesis at 4 university hospitals were included. Data were collected retrospectively from patient records and monitored by an independent party.

Results: Median follow-up time was 4.8 years. Mean CHADS-VASc score was 4.1 ± 1.6. Low (scores, 0-1), high (scores, 2-4), and very high (scores, 5-9) CHADS-VASc scores were observed in 39 (5.5%), 400 (56.0%), and 262 (38.5%) patients, respectively. Incidences of stroke or transient ischemic attack at 1 year were 2.6%, 4.8%, and 10.7%; at 5 years incidences were 5.2%, 14.0%, and 21.9%; and at 10 years incidence were 5.2%, 20.7%, and 37.9% for patients in low, high, and very high scores, respectively. Incidences of major bleeds at 1 year were 0%, 1.8%, and 2.7%; at 5 years incidences were 0%, 5.4%, and 8.7%; and at 10 years incidences were 0%, 9.0%, and 27.1%, respectively. Competing risk analysis showed that patients with CHADS-VASc score of 5 through 9 had a significantly increased risk of stroke or transient ischemic attack (hazard ratio, 4.75; 95% confidence interval, 1.09-20.6; P = .037) irrespective of preoperative or new-onset in-hospital atrial fibrillation compared with low-risk patients.

Conclusions: CHADS-VASc is a valuable tool to identify patients with increased risk of stroke and major bleeding, and for whom alternative strategies for prevention of late neurologic complications should be adopted.
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http://dx.doi.org/10.1016/j.jtcvs.2018.06.096DOI Listing
March 2019

Thromboembolisms related to post-operative electrical cardioversions for atrial fibrillation in patients with surgical aortic valve replacement.

Eur Heart J Qual Care Clin Outcomes 2018 04;4(2):120-125

Heart and Lung Center, Helsinki University Hospital and University of Helsinki, Internal Medicine, Helsinki, Finland.

Aims: Post-operative atrial fibrillation (POAF) is a frequent complication after open-heart surgery, and cardioversions (CV) are commonly performed to restore sinus rhythm. However, little data exists on thrombo-embolic risk related to early post-operative CV and on the recurrence of POAF after CV. CAREAVR study sought to assess the rate of strokes, transient ischaemic attacks (TIA), and mortality shortly after POAF-triggered CV in patients who underwent isolated surgical aortic valve replacement (SAVR) with a bioprosthesis.

Methods And Results: Altogether 721 patients underwent isolated SAVR with a bioprosthesis at four Finnish university hospitals. During post-operative hospitalization, after patients with prior chronic AF were excluded, 309/634 (48.7%) of patients had at least one episode of POAF [median time (interquartile range) 3 (3) days], and an electrical CV was performed in 113/309 (36.6%) of them. The length of hospital stay was not affected by CV. At 30 days follow-up, the rate of stroke, TIA or mortality was higher in those AF patients who underwent CV vs. those who did not (9.7% vs. 3.6%, P = 0.04, respectively; adjusted hazard ratio 2.63, 95% confidence interval 1.00-6.92, P = 0.05). Similar proportion of patients in both groups were in AF rhythm at discharge (32.7% vs. 35.7%, P = 0.18); and at 3 months (25.0% vs. 23.6%, P = 0.40), respectively.

Conclusion: In this real-world population of patients undergoing isolated SAVR, the rate of POAF was nearly 50%. One-third of these patients underwent an electrical CV, and they exhibited over two-fold risk for thromboembolisms and mortality. Cardioversion did not affect the short-term prevalence of AF.
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http://dx.doi.org/10.1093/ehjqcco/qcy003DOI Listing
April 2018

Systemic Dosing of Thymosin Beta 4 before and after Ischemia Does Not Attenuate Global Myocardial Ischemia-Reperfusion Injury in Pigs.

Front Pharmacol 2016 3;7:115. Epub 2016 May 3.

Research Center of Applied and Preventive Cardiovascular Medicine, University of Turku Turku, Finland.

The use of cardiopulmonary bypass (CPB) and aortic cross-clamping causes myocardial ischemia-reperfusion injury (I-RI) and can lead to reduced postoperative cardiac function. We investigated whether this injury could be attenuated by thymosin beta 4 (TB4), a peptide which has showed cardioprotective effects. Pigs received either TB4 or vehicle and underwent CPB and aortic cross-clamping for 60 min with cold intermittent blood-cardioplegia and were then followed for 30 h. Myocardial function and blood flow was studied by cardiac magnetic resonance and PET imaging. Tissue and plasma samples were analyzed to determine the amount of cardiomyocyte necrosis and apoptosis as well as pharmacokinetics of the peptide. In vitro studies were performed to assess its influence on blood coagulation and vasomotor tone. Serum levels of the peptide were increased after administration compared to control samples. TB4 did not decrease the amount of cell death. Cardiac function and global myocardial blood flow was similar between the study groups. At high doses a vasoconstrictor effect on mesentery arteries and a vasodilator effect on coronary arteries was observed and blood clot firmness was reduced when tested in the presence of an antiplatelet agent. Despite promising results in previous trials the cardioprotective effect of TB4 was not demonstrated in this model for global myocardial I-RI.
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http://dx.doi.org/10.3389/fphar.2016.00115DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4853610PMC
May 2016

Is emergency and salvage coronary artery bypass grafting justified? The Nordic Emergency/Salvage coronary artery bypass grafting study.

Eur J Cardiothorac Surg 2016 May 17;49(5):1451-6. Epub 2015 Nov 17.

Department of Cardiothoracic Surgery, Landspitali University Hospital and Faculty of Medicine, University of Iceland, Reykjavík, Iceland

Objectives: According to the EuroSCORE-II criteria, patients undergoing emergency coronary artery bypass grafting (CABG) are operated on before the beginning of the next working day after decision to operate while salvage CABG patients require cardiopulmonary resuscitation en route to the operating theatre. The objective of this multicentre study was to investigate the efficacy of emergency and salvage CABG.

Methods: A retrospective analysis of all patients that underwent emergency or salvage CAGB at four North-European university hospitals from 2006 to 2014.

Results: A total of 614 patients; 580 emergency and 34 salvage CABG patients (mean age 67 ± 10 years, 56% males) were included. All patients had an acute coronary syndrome: 234 (38%) had an ST segment elevation myocardial infarction (STEMI) and 289 (47%) had a non-STEMI. Haemodynamic instability requiring inotropic drugs and/or intra-aortic balloon pump preoperatively occurred in 87 (14%) and 82 (13%) of the patients, respectively. Three hundred and thirty-one patient (54%) were transferred to the operating room immediately after angiography and 205 (33%) had a failure of an attempted percutaneous coronary intervention. Cardiopulmonary resuscitation within 1 h before the operation was performed in 49 patients (8%), and 9 patients (1%) received cardiac massage during sternotomy. Hospital mortality for emergency and salvage operations was 13 and 41%, respectively. Early complications included reoperation for bleeding (15%), postoperative stroke (6%) and de novo dialysis for acute kidney injury (6%). Overall 5-year survival rate was 79% for emergency operations and 46% for salvage operations. Only one out of 9 patients receiving cardiac massage during sternotomy survived.

Conclusions: Early mortality in patients undergoing emergent and salvage CABG is substantial, especially in salvage patients. Long-term survival is acceptable in both emergent and salvage patients. Life-saving emergency and salvage CABG is justified in most patients but salvage patients have dismal prognosis if cardiac massage is needed during sternotomy.
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http://dx.doi.org/10.1093/ejcts/ezv388DOI Listing
May 2016

Thirty-year results after implantation of the Björk-Shiley Convexo-Concave Heart valve prosthesis.

Ann Thorac Surg 2014 Feb 6;97(2):552-6. Epub 2013 Nov 6.

Heart Center, Turku University Hospital and University of Turku, Turku, Finland.

Background: Modifications of the Björk-Shiley valve prosthesis have shown good long-term results. The convexo-concave model, however, was recalled 27 years ago because of a propensity for breakage due to outlet strut fracture. The objective of this study is to describe the 30-year outcome after implantation of the Björk-Shiley convexo-concave mechanical heart valve prosthesis (Pfizer, Rye Brook, NY).

Methods: The study included 279 patients who were operated between 1979 and 1983 at Turku University Hospital. A total of 305 valves were implanted; 205 in the aortic position and 100 in the mitral position. Patient records were reviewed for baseline characteristics and late events, data on mortality were acquired from registries.

Results: Mean actuarial survival was 19.8 years and mean follow-up was 19.2 years (maximum 34 years). Freedom from reoperation was 91.3% at 30 years. There were 3 outlet strut fractures (2 fatal) during follow-up. Statistically significant predictors of mortality were age and concomitant coronary artery bypass grafting.

Conclusions: Despite the possibility of structural valve failure the Björk-Shiley convexo-concave valve confers excellent 30-year survival.
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http://dx.doi.org/10.1016/j.athoracsur.2013.09.032DOI Listing
February 2014

Intracoronary Levosimendan during Ischemia Prevents Myocardial Apoptosis.

Front Physiol 2012 14;3:17. Epub 2012 Feb 14.

Department of Surgery, Turku University Hospital Turku, Finland.

Background: Levosimendan is a calcium sensitizer that has been shown to prevent myocardial contractile depression in patients post cardiac surgery. This drug exhibits an anti-apoptotic property; however, the underlying mechanism remains elusive. In this report, we characterized the myocardial protective of levosimendan in preventing cardiomyocyte apoptosis and post-operative stunning in an experimental ischemia-reperfusion model.

Methods: Three groups of pigs (n = 8 per group) were subjected to 40 min of global, cardioplegic ischemia followed by 240 min of reperfusion. Levosimendan (65 μg/kg body weight) was given to pigs by intravenous infusion (L-IV) before ischemia or intracoronary administration during ischemia (L-IC). The Control group did not receive any levosimendan. Echocardiography was used to monitor cardiac function in all groups. Apoptosis levels were assessed from the left ventricle using the terminal transferase mediated dUTP nick end labeling (TUNEL) assay and immunocytochemical detection of Caspase-3.

Results: Pigs after ischemia-reperfusion had a much higher TUNEL%, suggesting that our treatment protocol was effective. Levels of apoptosis were significantly increased in Control pigs that did not receive any levosimendan (0.062 ± 0.044%) relative to those received levosimendan either before (0.02 ± 0.017%, p = 0.03) or during (0.02 ± 0.017%, p = 0.03) the ischemia phase. Longitudinal left ventricular contraction in pigs that received levosimendan before ischemia (0.75 ± 0.12 mm) was significantly higher than those received levosimendan during ischemia (0.53 ± 0.11 mm, p = 0.003) or Control pigs (0.54 ± 0.11 mm, p = 0.01).

Conclusion: Our results suggested that pigs received levosimendan displayed a markedly improved cell survival post I-R. The effect on cardiac contractility was only significant in our perfusion heart model when levosimendan was delivered intravenously before ischemia.
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http://dx.doi.org/10.3389/fphys.2012.00017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3278776PMC
October 2012

Cardiomyocyte apoptosis after antegrade and retrograde cardioplegia during aortic valve surgery.

Ann Thorac Surg 2011 Oct;92(4):1351-7

Department of Surgery, Turku University Hospital, University of Turku, Turku, Finland.

Background: Retrograde delivery is associated with inadequate perfusion of cardioplegia to all regions of the heart, but the effects on cardiomyocyte death and functional outcome remain unknown. We compared antegrade and retrograde cardioplegia in a randomized clinical trial to see whether it has effect on cardiomyocyte apoptosis and left ventricular function.

Methods: Patients underwent elective aortic valve replacement surgery due to aortic valve stenosis. They were randomly allocated to receive antegrade (n = 10) or retrograde (n = 10) cardioplegia. Apoptotic cardiomyocytes (terminal transferase-mediated dUTP nick end labeling, caspase activation) and RNA levels of apoptosis-regulating proteins were studied in transmyocardial biopsies obtained before and after the operation. Magnetic resonance imaging and transesophageal echocardiography were performed, and cardiac enzymes were measured.

Results: Clinical outcome and cardiac enzyme release were comparable between the groups. Cardiomyocyte apoptosis was significantly increased (terminal transferase-mediated dUTP nick end labeling) in the left ventricle after the operation in the retrograde, but not in the antegrade group (respectively, 0.00% [0.039%] versus 0.092% [0.205%], p = 0.01; and 0.00% [0.00%] versus 0.023% [0.054%], p = 0.14). Expression of apoptosis-regulating proteins BAX, BAD, and BCL-2 were comparable between groups. By transesophageal echocardiography, the systolic mitral annulus movement was decreased immediately after the operation in the retrograde group. By magnetic resonance imaging, the left ventricle mass index was reduced preoperatively to 9 months postoperatively in the antegrade group.

Conclusions: In contrast to antegrade cardioplegia, retrograde cardioplegia is associated with increased cardiomyocyte apoptosis, impaired immediate postoperative systolic function, and lack of long-term favorable left ventricle remodeling after aortic valve replacement, suggesting inadequate myocardial protection.
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http://dx.doi.org/10.1016/j.athoracsur.2011.05.065DOI Listing
October 2011

Cardiomyocyte apoptosis and duration of aortic clamping in pig model of open heart surgery.

Eur J Cardiothorac Surg 2006 Sep 20;30(3):480-4. Epub 2006 Jul 20.

Research Centre of Applied and Preventive Cardiovascular Medicine, Turku University, FIN-20520 Turku, Finland.

Objective: Apoptotic cardiomyocyte death is induced during open heart surgery, but its determinants are poorly understood. Prolonged aortic clamping time is associated with adverse clinical outcomes. The purpose of this study was to determine whether occurrence of cardiomyocyte apoptosis is related to the duration of aortic clamping in experimental pig model of cardiac surgery with cardiopulmonary bypass.

Methods: The pigs (mean weight 29 +/- 1 kg) were randomly divided to undergo cardioplegic arrest for 60 (n = 4) or 90 (n = 4) min followed by reperfusion period of 120 min. Control group (n = 5) was connected to cardiopulmonary bypass for 120 min without cardioplegic arrest. Cardiomyocyte apoptosis was detected (TUNEL assay and immunohistochemical staining of active caspase-3) in left ventricular tissue samples obtained before ischemia and after the ischemia-reperfusion period.

Results: Apoptotic cardiomyocytes were found in all samples obtained after cardioplegic arrest and cardiopulmonary bypass alone with the TUNEL assay. The amount of apoptosis after the 120 min of cardiopulmonary bypass alone in the control group was 0.006 +/- 0.001%. Compared with this, cardiomyocyte apoptosis was increased after cardioplegic arrest. After 60 min of aortic cross-clamp the amount of apoptosis was 0.019 +/- 0.004% (p = 0.031). After 90 min of aortic cross-clamp the amount was 0.042 +/- 0.005% (p < 0.001) being significantly higher than after 60 min (p = 0.001). Aortic cross-clamp of 90 min also resulted in a detectable increase in caspase-3 activation when compared with controls.

Conclusions: The occurrence of cardiomyocyte apoptosis increases with prolonged aortic clamping time during open heart surgery.
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http://dx.doi.org/10.1016/j.ejcts.2006.06.003DOI Listing
September 2006

Cardiomyocyte apoptosis after antegrade and retrograde cardioplegia.

Ann Thorac Surg 2005 Dec;80(6):2229-34

Department of Cardiothoracic Surgery, Turku University Central Hospital, Turku, Finland.

Background: Retrograde cardioplegia alone is often used in aortic valve and aortic root surgery. Due to the differences in venous anatomy between the right and the left side of the heart, retrograde cardioplegia is associated with incomplete protection of the right side. Since some apoptotic cardiomyocyte death is inevitable during an open heart surgery, we compared the extent of cardiomyocyte apoptosis in the left and right ventricles after antegrade and retrograde cardioplegia in a pig ischemia-reperfusion model.

Methods: Pigs (n = 16, mean weight 30 kg) were openly assigned into the groups of antegrade and retrograde cardioplegia. After aortic cross-clamping, 500 mL of cold crystalloid (modified St Thomas) cardioplegia was administered into the ascending aorta or the coronary sinus. Aortic cross-clamp time was 30 minutes. Cardiomyocyte apoptosis was measured using the terminal transferase mediated ddUTP nick end-labeling (TUNEL) assay and immunohistochemical (IHC) staining for active caspase-3 in myocardial biopsies obtained before ischemia and after 90 minutes of reperfusion.

Results: Apoptotic cardiomyocytes were significantly increased after ischemia-reperfusion as shown by both the TUNEL assay and caspase-3 activation. In the right ventricle, retrograde cardioplegia was associated with a 3.4-fold higher amount (TUNEL assay) of apoptotic cardiomyocytes as compared with antegrade cardioplegia (0.107% vs 0.032%, p < 0.05). A similar difference was also found in the left ventricle, although at a lower level (0.027% vs 0.012%, p < 0.05).

Conclusions: Increased apoptotic death of cardiomyocytes after retrograde cardioplegia as compared with the antegrade procedure implicates that retrograde cardioplegia alone provides inferior cardioprotection against irreversible ischemia-reperfusion injury both in the right and the left ventricle.
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http://dx.doi.org/10.1016/j.athoracsur.2005.05.057DOI Listing
December 2005