Prolonged Systemic Inflammatory Response Syndrome After Cardiac Surgery.

OBJECTIVES: Cardiac surgery induces systemic inflammatory response syndrome (SIRS), leading to higher morbidity and mortality. There are no individualized predictors for worse outcomes or biomarkers for the multifactorial, excessive inflammatory response. The interest of this study was to evaluate whether a systematic use of the SIRS criteria could be used to predict postoperative outcomes beyond infection and sepsis, and if the development of an exaggerated inflammation response could be observed preoperatively. DESIGN: The study was observational, with prospectively enrolled patients. SETTING: This was a single institution study in a hospital setting combined with laboratory findings. PARTICIPANTS: The study included a cohort of 261 volunteer patients. INTERVENTIONS: Patients underwent cardiac surgery with cardiopulmonary bypass, and were followed up to 90 days. Biomarker profiling was run preoperatively. MEASUREMENTS AND MAIN RESULTS: Altogether, 17 of 261 (6.4%) patients had prolonged SIRS, defined as fulfilling at least 2 criteria on 4 consecutive postoperative days. During hospitalization, postoperative atrial fibrillation (POAF) was found in 42.2% of patients, and stroke and transient ischemic attack in 3.8% of patients. Prolonged SIRS was a significant predictor of POAF (odds ratio [OR] 4.5, 95% CI 1.2-17.3), 90-day stroke (OR 4.5, 95% CI 1.1-18.0), and mortality (OR 10.7, 95% CI 1.7-68.8). Biomarker assays showed that preoperative nerve growth factor and interleukin 5 levels were associated with prolonged SIRS (OR 5.6, 95%, CI 1.4-23.2 and OR 0.7, 95%, CI 0.4-1.0, respectively). CONCLUSIONS: Nerve growth factor and interleukin 5 can be used to predict prolonged systemic inflammatory response, which is associated with POAF, stroke, and mortality.

Antithrombotic Medication and Major Complications After Mechanical Aortic Valve Replacement.

Patients with mechanical aortic valve replacement (AVR) require lifelong vitamin K antagonist (VKA) therapy for stroke and systemic embolism prevention. However, VKA treatment predisposes patients to various types of bleeding. In the present study, we sought to assess the success of antithrombotic therapy and the occurrence and timing of strokes and bleeding events after mechanical AVR. A total of 308 patients who underwent isolated mechanical AVR were included in the study, and follow-up data were completed for 306 patients (99.4%). The median follow-up time was 7.3 (interquartile range 4.2 to 10.9) years. The risk for major bleeding was 5-fold compared with major stroke (6.2% vs 1.3% and 20.9% vs 4.0%, respectively; events rates 3.1 vs 0.5 per 100 patient-years, respectively) at 30-day and long-term follow-up, indicating good efficacy but inadequate safety of stroke prevention. At the time of the early postoperative major bleeding, the international normalized ratio was under the therapeutic range in 73.7% of the patients. However, most patients were on triple antithrombotic treatment consisting of subcutaneous enoxaparin, VKA, and a tail effect of discontinued aspirin. During the long-term follow-up, the most common site of bleeding was gastrointestinal (41.7%), followed by genitourinary bleeding (23.3%) and intracranial hemorrhage (18.3%). Furthermore, mortality was relatively high, with a 10-year survival estimate of 78.3%. In conclusion, although ischemic stroke is a well-identified adverse event after mechanical AVR, it seems that major bleeding is a frequent clinically relevant complication during perioperative and long-term follow-up. This finding underscores the recognition and management of modifiable bleeding risk factors.

Risk of fluid accumulation after cardiac surgery.

Objective: Patients undergoing heart surgery are at high risk of postoperative fluid accumulation due to long procedures and cardiopulmonary bypass. In the present study, we sought to investigate the prevalence of postoperative fluid accumulation and its relation to adverse events in patients undergoing cardiac surgery. Methods: CAREBANK is prospective, single-center cohort study focusing on the adverse events after cardiac surgery. The study population was divided into 2 groups based on 5% postoperative weight gain. All the in-hospital adverse events are registered on the database. The end points of the present study were length of hospital stay, length of intensive care unit stay, occurrence of new-onset atrial fibrillation after hospital major bleeding episodes major cardiac events, cerebrovascular events, and death. Three-month and 1-year follow-up data also include all major adverse events. Results: Altogether 1001 adult cardiac surgery patients were enrolled. The most frequent operations were coronary artery bypass grafting (56.3%). Five hundred fifty-four out of 939 (59.0%) patients had ≥5% weight gain during index hospitalization. Patients with a weight gain ≥5% were more likely to be women, have lower body mass index, had heart failure, and more often had preoperative atrial fibrillation. In-hospital period fluid accumulation was associated with reoperation due bleeding and longer total hospital stay. At 3 months' follow-up, weight gain 5% or more was associated with increased occurrence of new-onset atrial fibrillation, this was not reflected in the occurrence of strokes, transient ischemic attacks, or myocardial infarctions. Conclusions: Postoperative fluid excess is associated with adverse outcomes in cardiac surgery. Women, low-weight patients, and patients with cardiac failure or atrial fibrillation are prone to perioperative fluid accumulation.

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

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.

Red blood cell transfusion induces abnormal HIF-1α response to cytokine storm after adult cardiac surgery.

Patients undergoing cardiac surgery develop a marked postoperative systemic inflammatory response. Blood transfusion may contribute to disruption of homeostasis in these patients. We sought to evaluate the impact of blood transfusion on serum interleukin-6 (IL-6), hypoxia induced factor-1 alpha (HIF-1α) levels as well as adverse outcomes in patients undergoing adult cardiac surgery. We prospectively enrolled 282 patients undergoing adult cardiac surgery. Serum IL-6 and HIF-1α levels were measured preoperatively and on the first postoperative day. Packed red blood cells were transfused in 26.3% of patients (mean 2.93 ± 3.05 units) by the time of postoperative sampling. Postoperative IL-6 levels increased over 30-fold and were similar in both groups (p = 0.115), whilst HIF-1α levels (0.377 pg/mL vs. 0.784 pg/mL, p = 0.002) decreased significantly in patients who received red blood cell transfusion. Moreover, greater decrease in HIF-1α levels predicted worse in-hospital and 3mo adverse outcome. Red blood cell transfusion was associated with higher risk of major adverse outcomes (stroke, pneumonia, all-cause mortality) during the index hospitalization. Red blood cell transfusion induces blunting of postoperative HIF-1 α response and is associated with higher risk of adverse thrombotic and pulmonary adverse events after cardiac surgery. Clinical Trial Registration ClinicalTrials.gov Identifier: NCT03444259.

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

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.

Postpericardiotomy syndrome after cardiac surgery.

Postpericardiotomy syndrome (PPS) is a well-known complication after cardiac surgery. The syndrome results in prolonged hospital stay, readmissions, and invasive interventions. Previous studies have reported inconsistent results concerning the incidence and risk factors for PPS due to the differences in the applied diagnostic criteria, study designs, patient populations, and procedure types. In recent prospective studies the reported incidences have been between 21 and 29% in adult cardiac surgery patients. However, it has been stated that most of the included diagnoses in the aforementioned studies would be clinically irrelevant. This challenges the specificity and usability of the currently recommended diagnostic criteria for PPS. Moreover, recent evidence suggests that PPS requiring invasive intervention such as the evacuation of pleural and/or pericardial effusion is associated with increased mortality. In the present review, we summarise the existing literature concerning the incidence, clinical features, diagnostic criteria, risk factors, management, and prognosis of PPS. We also propose novel approaches regarding to the definition and diagnosis of PPS. Key messages: Current diagnostic criteria of PPS should be reconsidered, and the analyses should be divided into subgroups according to the severity of the syndrome to achieve more clinically applicable and meaningful results in the future studies. In contrast with the previous presumption, severe PPS - defined as PPS requiring invasive interventions - was recently found to be associated with higher all-cause mortality during the first two years after cardiac surgery. The association with an increased mortality supports the use of relatively aggressive prophylactic methods to prevent PPS. The risk factors clearly increasing the occurrence of PPS are younger age, pleural incision, and valve and ascending aortic procedures when compared to CABG.

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

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 CHA2 DS2 -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.

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

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.

Performance of CHA2DS2-VASc score for stroke prediction after surgical aortic valve replacement.

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) (CHA2DS2-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 CHA2DS2-VASc score was 4.1 ± 1.6. Low (scores, 0-1), high (scores, 2-4), and very high (scores, 5-9) CHA2DS2-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 CHA2DS2-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: CHA2DS2-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.

Occurrence of Postpericardiotomy Syndrome: Association With Operation Type and Postoperative Mortality After Open-Heart Operations.

Background Postpericardiotomy syndrome ( PPS ) is a common complication after cardiac surgery. However, large-scale epidemiological studies about the effect of procedure type on the occurrence of PPS and mortality of patients with PPS have not yet been performed. Methods and Results We studied the association of PPS occurrence with operation type and postoperative mortality in a nationwide follow-up analysis of 28 761 consecutive patients entering coronary artery bypass grafting, aortic valve replacement, mitral valve replacement, or ascending aortic surgery. Only PPS episodes severe enough to result in hospital admission or to contribute as a cause of death were included. Data were collected from mandatory Finnish national registries between 2005 and 2014. Of all the patients included, 493 developed PPS during the study period. The occurrence of PPS was significantly higher after aortic valve replacement (hazard ratio, 1.97; 95% confidence interval, 1.58-2.46; P<0.001), mitral valve replacement (hazard ratio, 1.62; 95% confidence interval, 1.22-2.15; P<0.001), and aortic surgery (hazard ratio, 3.06; 95% confidence interval, 2.24-4.16; P<0.001), when compared with coronary artery bypass grafting in both univariable and multivariable analyses. The occurrence of PPS decreased significantly with aging ( P<0.001). The occurrence of PPS was associated with an increased risk of mortality within the first year after the surgery (adjusted hazard ratio, 1.78; 95% confidence interval, 1.12-2.81; P=0.014). Conclusions The occurrence of PPS was higher after aortic valve replacement, mitral valve replacement, and aortic surgery when compared with the coronary artery bypass grafting procedure. Aging decreased the risk of PPS . The development of PPS was associated with higher mortality within the first year after cardiac or ascending aortic surgery.

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

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.

Postpericardiotomy syndrome.

Postpericardiotomy syndrome (PPS) is a common complication following cardiac surgery. In most cases it develops 2 to 3 weeks after the operation. An inflammatory reaction develops in the pericardium or pleural space with fever, chest pain and dyspnea as typical symptoms. The disease process is usually self-limiting. At present, the etiology is unknown, but an immunological mechanism is suspected as the cause of the disease. The incidence of PPS is essentially dependent on diagnostic criteria, patient group and type of operation. Treatment is carried out with anti-inflammatory analgesics, combined with colchicine in more severe cases.

Occurrence of postpericardiotomy syndrome admissions: A population-based registry study.

BACKGROUND: Postpericardiotomy syndrome (PPS) is a common complication after cardiac surgery. Previous epidemiological descriptions of the syndrome, however, are scarce. MATERIAL AND METHODS: This retrospective analysis included all patients hospital admission due to PPS in patients aged 20-79 years. Data were collected from the Finnish national registry that included data on all cardiovascular hospital admissions (n = 51 7669) during 9.5 years in 29 Finnish hospitals nationwide. RESULTS: There were 760 hospital admissions due to PPS during the study period. The patients were more likely male than female (67.8% versus 32.2%) with an age-adjusted RR of 2.37 (95% CI 1.85-3.02) for men (p < 0.0001). When evaluating the rate of PPS in relation to cardiac surgeries, female gender was associated with a higher incidence of PPS (RR 1.78; 95% CI 1.45-2.19; p < 0.001). The rate of PPS in relation to the number of cardiac surgery was highest in youngest patients followed by a gradual decrease (RR 0.59; 95% CI 0.55-0.65; p < 0.0001 per 10-year increment in age) with aging. CONCLUSIONS: Hospital admission due to PPS was most common in men in their sixties. When stratified by the total number of performed cardiac operations the incidence of PPS was higher among women and younger patients.

Incidence and risk factors of postpericardiotomy syndrome requiring medical attention: The Finland postpericardiotomy syndrome study.

OBJECTIVES: Postpericardiotomy syndrome is a well-known complication after cardiac surgery. Nevertheless, little is known about the incidence and predictors of postpericardiotomy syndrome requiring medical attention or hospitalization in a contemporary set of patients undergoing isolated coronary bypass. METHODS: This retrospective analysis included 688 patients from 2008 to 2010. The median follow-up time was 5.3 [4.5-6.0] years. RESULTS: The incidence of postpericardiotomy syndrome was 61 of 688 patients (8.9%), and the median time to diagnosis was 21 [11-52] days, but only 13 patients (22%) required pleural drainage and 3 patients (4.9%) required pericardiocentesis. Patients with postpericardiotomy syndrome more often had 1 or more red blood cell units transfused (61% vs 43%, P = .008) after surgery and less often had diabetes (12% vs 31% P = .002) or metformin medication (3.3% vs 20%, P = .001) compared with those without postpericardiotomy syndrome. In multivariable Cox regression model, renal insufficiency and 1 or more red blood cell units transfused remained as independent predictors of postpericardiotomy syndrome and diabetes remained as a protective factor. Incidence of recurrences was high (38%), and increasing body mass index was the only predictor of relapse. CONCLUSIONS: The incidence of symptomatic postpericardiotomy syndrome leading to medical care contact was markedly lower compared with that reported in older clinical studies. Postpericardiotomy syndrome was associated with the use of red blood cell units and was less common in patients with medically treated diabetes.