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Sex is suggested to influence outcomes after coronary artery bypass grafting (CABG), although evidence on long-term mortality is controversial and cardiovascular outcome data are lacking. We studied sex differences in outcomes after isolated CABG. Consecutive patients with first-time isolated CABG for stable coronary artery disease between 2004 and 2014 in Finland were retrospectively recognized from national registry (n = 14,681; 21% women). Propensity scoring and inverse probability weighting were used to adjust for baseline features. Median follow-up was 10.0 (maximum 14.6) years. Cumulative major adverse cardiovascular event (myocardial infarction, stroke, or cardiovascular death) rate was 44.5% in men and 49.9% in women during follow-up (hazard ratio [HR], 0.98; P =.633). All-cause mortality was 48.5% in men vs 46.0% in women (HR, 1.20; 95% confidence interval, 1.11-1.30; P <.0001), and cardiovascular mortality was 29.5% vs 31.3% (P =.625). Stroke rate was comparable between men and women (19.4% vs 23.6%; P =.625). Myocardial infarction occurred more frequently in women (20.0% vs 23.6%; HR, 0.84; 95% confidence interval, 0.75-0.95; P =.005). Redo revascularization was performed to 12.8% of women and to 12.6% of men (P =.100). Anticoagulation was more frequently used by men and adenosine diphosphate inhibitors and diuretics were more frequently used by women after CABG. Usage of statins, angiotensin-converting-enzyme inhibitors or angiotensin-blockers, beta-blockers, calcium-channel blockers, or nitrates did not differ between sexes after CABG. Sex was not an independent predictor of long-term major adverse cardiovascular events after CABG in this population-based cohort study. However, men had higher long-term all-cause mortality and women higher risk of myocardial infarction. Long-term outcomes should be accounted for when considering sex as a risk factor for CABG. [ABSTRACT FROM AUTHOR]

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. 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. 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. 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. Patients with severe PPS were at increased risk for mortality. A transient increased risk of new-onset AF was observed, but PPS had no effect on the occurrence of cerebrovascular events or major bleeds. [ABSTRACT FROM AUTHOR]

The use of biologic prosthesis is increasing in surgical aortic valve replacement (SAVR). Recent US guidelines recommend either biologic or mechanical prosthesis for SAVR in patients aged 50 to 70 years. We set out to study long-term outcomes of mechanical versus biologic prosthetic valves in this patient group. All patients (excluding infective endocarditis and concomitant surgery other than coronary artery bypass grafting) aged 50 to 70 with first-time SAVR in Finland between 2004 and 2014 were retrospectively studied (N = 2928). Propensity score matching (1:1) was used to identify patients with comparable baseline features (n = 1152). Outcomes were 10-year all-cause mortality, aortic valve reoperation, major bleeding, ischemic stroke, and infective endocarditis. Mean follow-up was 6.7 years. Ten-year all-cause mortality was 18.6% with mechanical valves and 27.6% with biologic valves (hazard ratio [HR], 0.72; 95% confidence interval [CI], 0.54-0.97; P =.028). Prosthetic valve reoperation was performed in 1.4% with mechanical valves and in 8.5% with bioprosthetic valves (HR, 0.30; 95% CI, 0.12-0.74; P =.009). Major bleeding occurred in 21.5% with mechanical valves and in 16.9% with biologic prostheses (HR, 1.19; P =.402). Rates of intracranial bleeding were also comparable. Ischemic stroke rates within 10 years were 12.7% with mechanical valves and 9.3% with biologic valves (HR, 1.29; P =.316). Infective endocarditis occurred in 3.7% of mechanical valves and in 7.3% of biologic valves (HR, 0.46; 95% CI, 0.24-0.88; P =.018). Mechanical valve prostheses were associated with lower mortality, lower rates of reoperation, and lower occurrence of infective endocarditis compared with bioprostheses within 10 years after SAVR in matched patients aged 50 to 70 years. Our results do not support the routine use of biologic valve prostheses in this patient group. [ABSTRACT FROM AUTHOR]

Women are considered to have poorer prognoses after cardiac surgery, although evidence is scarce. The authors studied sex differences and long-term outcomes after surgical aortic valve replacement (SAVR). Nationwide retrospective cohort study. Six public hospitals and 2 private hospitals. All first-time SAVR (±coronary artery bypass surgery) patients (excluding endocarditis) aged ≥18 with a prosthetic valve were retrospectively identified from a national registry (n = 7616). Propensity score matching identified 2814 men and 2814 women with comparable baseline features. No intervention. Outcomes were survival, major bleeding, ischemic stroke, infective endocarditis, and reoperation. Ten-year survival was 66.8% in men and 67.5% in women (hazard ratio [HR] 1.09; p = 0.107). Major bleeding occurred in 21.5% of men and 19.7% of women (HR 1.36; confidence interval [CI] 1.13-1.63; p = 0.0009) within 10 years, with similar results for mechanical and biological prosthesis. Bleeding was gastrointestinal in 38.5%, intracranial in 27.6%, and 33.9% in other sites with no sex difference in location. Ischemic stroke occurred in 12.5% of men and 13.3% of women within 10 years (HR 1.06; p = 0.614), and 4.7% of men and 2.6% of women (HR 1.77; CI 1.24-2.51; p = 0.001) had infective endocarditis, but association was present only with biological prosthesis (interaction p = 0.02). Aortic valve re-surgery was more common in men at 1 (HR 2.98; CI 1.27-7.00; p = 0.013) and 5 years after SAVR, but not at 10 years (2.4% v 3.8%; p = 0.189). Baseline-matched long-term survival after SAVR is similar between sexes. Men had increased risk of bleeding, early re-surgery after SAVR, and infective endocarditis when using biological prosthesis. [ABSTRACT FROM AUTHOR]

Biologic prostheses are preferred for surgical aortic valve replacement (SAVR) in patients more than 70 years of age in clinical practice. This study investigated differences in long-term outcomes between SAVR-treated patients more than 70 years of age who received mechanical or biologic prosthetic valves. All patients (excluding those with endocarditis) who were more than 70 years of age and who underwent isolated first-time SAVR (with or without coronary artery bypass grafting) in Finland between 2004 and 2014 were retrospectively studied (n = 4227). Propensity score matching (1:3) was used to account for baseline differences (n = 296 with mechanical prostheses and n = 888 with biologic prostheses). Outcomes were 10-year survival, major bleeding (all, gastrointestinal, intracranial), ischemic stroke, infective endocarditis, and aortic valve reoperation. Mean age was 75.8 years, and mean follow-up was 8.3 years. Survival at 10 years was 46.1% with mechanical prostheses and 57.8% with biologic prostheses (hazard ratio [HR], 1.48; 95% confidence interval [CI], 1.21 to 1.80; P <.001; number needed to harm = 7.0). The 10-year major bleeding rates were 37.0% with mechanical valves and 18.8% with biologic valves (HR, 1.77; 95% CI, 1.25 to 2.49; P =.001; number needed to harm = 7.4). Both gastrointestinal bleeding (26.5% vs 8.9%; HR, 2.63; 95% CI, 1.63 to 4.23; P <.001) and intracranial bleeding (8.8% vs 6.0%; HR, 2.12; 95% CI, 1.09 to 4.15; P =.028) were significantly more frequent with mechanical valve prosthesis. Occurrence of ischemic stroke (18.9% with mechanical prosthesis vs 16.1% with biologic prosthesis; P =.341), infective endocarditis (3.7% vs 2.8%; P =.242), or aortic valve reoperation (0.8% vs 2.8%; P =.707) did not differ between study groups. Mechanical aortic valve prosthesis is associated with worse long-term survival and increased bleeding after SAVR in patients more than 70 years old. The study results suggest caution when considering mechanical aortic valve prostheses in elderly patients. [ABSTRACT FROM AUTHOR]

Studies of long-term survival after minimally invasive and open esophagectomy are needed. The aim of this study was to compare long-term outcomes following minimally invasive and open esophagectomy for esophageal cancer at the population level. All patients undergoing minimally invasive (n = 159) or open transthoracic (n = 431) esophagectomy for esophageal cancer in Finland between 2004 and 2014 were identified from nationwide registries. Propensity score matching was used to create groups of 150 minimally invasive and open esophagectomies with balanced baseline characteristics (sex, age, comorbidity, center volume, year of surgery, histology, stage (local or locally advanced), and neoadjuvant therapy). The primary outcome was 1-year survival after surgery. Secondary outcomes were the 3-year, 5-year, and 90-day survival. The propensity matched 1-year survival rate was 85.3% after minimally invasive and 74.7% after open esophagectomy (adjusted HR 0.53, 95% CI 0.31–0.89; P = 0.0174). At 3 years, those were 68.7% and 55.6% (adjusted HR 0.62; 95% CI 0.43–0.91; P = 0.0144), respectively; at 5 years, survival rates were 61.8% and 51.9% (adjusted HR 0.68, 95% CI 0.47–0.97; P = 0.0347). The 30- and 90-day survival rates after minimally invasive and open surgery were 99.3% vs. 98.0% and 97.3% vs. 92.0%, respectively, without statistical significance. In this population-based propensity matched study, minimally invasive esophagectomy was associated with improved long-term survival. Due to multiple confounding factors replication studies are needed. [ABSTRACT FROM AUTHOR]

Objectives To investigate whether adding carvedilol, a nonselective β- and selective α 1 -receptor blocking agent with antioxidant properties, to oxygenated blood cardioplegia improves myocardial function after weaning from bypass. Design A randomized controlled study. Setting A university laboratory. Participants Twenty anesthetized pigs, Norwegian Landrace. Interventions On cardiopulmonary bypass, cardiac arrest was induced with cold (12°C), oxygenated blood cardioplegia, enriched with carvedilol or vehicle, and repeated every 20 minutes. After 100 minutes, the heart was reperfused and weaned. Measurements and Main Results Left ventricular function was evaluated with pressure-volume loops, local myocardial systolic strain, and strain rate from Speckle tracking analysis and multilayer short-axis tissue Doppler Imaging. In the carvedilol group, the load-independent logarithmic end-diastolic pressure volume relationship, β, decreased from 1 to 3 hours of reperfusion and was low, 0.028±0.004 v 0.042±0.007 (p<0.05) in controls at 3 hours, demonstrating improved left ventricular compliance. The diastolic relaxation constant τ was decreased, 28.9±0.6 ms v 34.6±1.3 ms (p g <0.035), and dP/dt min was more negative,−1,462±145 mmHg/s v−1,105±105 mmHg/s (p g = 0.024), for carvedilol v control group. The systolic variables, preload recruitable stroke work and end-systolic pressure-volume relationship, did not differ between groups, neither did left ventricular systolic strain and strain rate. Myocardial oxidative stress, measured as tissue levels of malondialdehyde, was reduced by carvedilol, 0.19±0.01 compared to 0.24±0.01 nmol/mg (p = 0.004) in controls. Conclusions Carvedilol added to blood cardioplegia improved diastolic cardiac function and reduced oxidative stress during the first 3 hours after reperfusion in a porcine model, with 100 minutes of cardioplegic arrest. [ABSTRACT FROM AUTHOR]

Previous studies have suggested that women may be at higher risk of death after ST-segment elevation myocardial infarction (STEMI). We studied potential associations of gender and age with in-hospital mortality using a registry of 31,689 consecutive patients with STEMI aged ≥30 years (66.3% men, mean age 67.8 years) treated in 22 hospitals. Total in-hospital mortality rate of STEMI was 11.2%. Women had higher unadjusted mortality rate compared with men (17.5% vs 8.0%; hazard ratio 1.65; 95% confidence interval [CI] 1.54 to 1.76, p <0.0001). However, when adjusted for age and co-morbidities, there was no difference in mortality between genders overall (hazard ratio 1.04; 95% CI 0.97 to 1.12, p[0.2303) or at any age group. Mortality rate was highly dependent of age with an estimated increase of 86% (95% CI 80% to 92%) per 10-year increase in age (p <0.0001). Chronic coronary, peripheral, or cerebral artery disease, diabetes, renal insufficiency, malignancy, and severe infection were independent predictors of mortality in multivariate analysis. Atrial fibrillation was associated with survival in multivariate model. Anterior location of STEMI was not independently associated with in-hospital mortality. In conclusion, although women have higher total in-hospital mortality rate than men after STEMI, this difference does not appear to be caused by gender itself but to be due to of differences in age and co-morbidities. [ABSTRACT FROM AUTHOR]

Background Rate and patient features associated with recurrence after acute myocarditis are largely unknown. Methods and results First recurrence of acute myocarditis was studied in 1662 patients aged 16–70 years using a registry data of 29 hospitals in Finland (median follow-up 4.5 years). Matched intoxication patients served as controls. Incidence rate of first time hospitalization due to acute myocarditis was 5.52 (CI 5.26–5.79) per 100,000 person-years during 2001–2008. During the first 30 days 5.5% (CI 3.5–4.4%) of patients were re-admitted to hospital with acute myocarditis ( p < 0.0001 vs. controls). After 30 days, recurrence rate was 7.0% (CI 5.7–8.6%; p < 0.0001 vs. controls). Acute myocarditis recurred after 365 days in 4.7% (CI 3.2–6.7%) of patients ( p < 0.0001 vs. controls). During the whole follow-up, recurrence rate was 10.3% (CI 8.8–12.1%; p < 0.0001 vs. controls) with median recurrence time of 34.5 days. Prolonged (> 7 days) initial admission was associated with recurrences during (HR 2.9; CI 1.6–5.2) and after first month (HR 1.8; CI 1.2–3.2), and overall (HR 2.0; CI 1.3–3.2). Ventricular arrhythmia at initial occurrence was associated with recurrence after 30 days (HR 8.6; CI 2.5–30.1), after 1 year (HR 22.6; CI 2.5–201.4) and overall (HR 6.7; CI 2.3–6.7). Other features associated with recurrence were younger age (> 365 days), inflammatory bowel disease (during first month), and chronic pulmonary disease (≥ 30 days). Conclusions Acute myocarditis reoccurs in a significant proportion of patients. Prolonged initial admission, ventricular arrhythmias, younger age, inflammatory bowel disease and chronic pulmonary disease are associated with recurrences at different phases after acute myocarditis. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Genetically modified hyperlipidemic mice are increasingly used as an animal model of atherosclerosis, but their coronary artery disease remains poorly characterized. Furthermore, non-invasive tools to detect functional consequences of coronary lesions remain to be tested in mice. Coronary flow velocity reserve (CFVR) by transthoracic Doppler echocardiography provides a hemodynamic measure of coronary artery stenosis severity in humans. Thus, we applied Doppler echocardiography in atherosclerotic mice to study the relationship between CFVR and histologically determined coronary artery narrowing. Methods: Atherosclerotic LDLR/ApoB48 double knockout mice of 58–72 weeks age (n =12) and age-matched C57BL/6 mice (n =5) were studied. CFVR was measured in anesthetized mice by Doppler echocardiography in the middle left coronary artery (LCA) during adenosine-induced maximal vasodilatation. Histopathology of proximal and middle LCA was studied in serial tissue sections. Results: All LDLR/ApoB48 double knockout mice had atherosclerotic lesions in the proximal, but not in the middle LCA causing various degrees of luminal narrowing (30–97%). No lesions were found in controls. Compared with controls, CFVR was significantly reduced in the atherosclerotic mice (2.3±0.5 vs. 1.7±0.5, p =0.02). There was a negative correlation between CFVR and the amount of luminal narrowing (r =−0.91, p =0.001). Average CFVR was consistently lower in mice that had ≥70% than <70% stenosis (1.3±0.1, n =7 vs. 2.2±0.4, n =5, p =0.0002). Conclusions: LDLR/ApoB48 double knockout mice are characterized with histologically severe coronary artery narrowings. Reduced CFVR is a consistent feature of these lesions. Doppler echocardiography of coronary artery flow can be used to detect flow-limiting stenosis in living atherosclerotic mice. [Copyright &y& Elsevier]

Objective: Transient left-ventricular dysfunction because of myocardial reperfusion injury is a significant problem after cardiac surgery, but the underlying complex pathophysiology is still poorly understood. The authors studied early functional recovery of the postischemic myocardium and explored potential effects of thrombin inhibition on procoagulatory, proinflammatory, and proapoptotic features of myocardial ischemia-reperfusion injury. Design: A randomized, blinded study. Setting: University research laboratory. Subjects: Porcine model. Interventions: Twenty pigs undergoing 60 minutes of aortic clamping and 75 minutes of normothermic cardiopulmonary bypass (CPB) received an intravenous bolus of r-hirudin (10 mg, 0.4mg/kg, n = 10) or placebo (n = 10) 15 minutes before aortic declamping, followed by a 135-minute intravenous infusion of r-hirudin (3.75 mg, 0.15 mg/kg/h) or placebo. Measurements and Main Results: Hemodynamic parameters were measured before CPB, after weaning from CPB, and at 30, 60, 90, and 120 minutes after aortic declamping. Blood was sampled, and myocardial biopsies were taken before CPB, just before aortic declamping, during reperfusion, and after 120 minutes of reperfusion to measure thrombin antithrombin complexes and to quantitate leukocyte infiltration (myeloperoxidase activity) for histologic evaluation and detection of apoptosis with caspase-3 and the TUNEL method. The r-hirudin group showed significantly higher stroke volume and cardiac output than the control group at 60 minutes and at 90 minutes after aortic declamping (p < 0.05). Microthrombosis was not observed in either group, indicating sufficient anticoagulation and excluding intravascular clots as explanations for LV dysfunction in the current experiment. Instead, ample myocardial activation of inflammation was present, but only a trend of r-hirudin–associated anti-inflammatory effect was observed. Compared with the controls, TUNEL-positive myocytes were detected significantly less frequently in the r-hirudin group (0.05 ± 0.06 v 0.13 ± 0.07 TUNEL-positive nuclei %, p = 0.042). Conclusions: The improved cardiac recovery in the r-hirudin group during reperfusion after cardioplegia-induced cardiac arrest was associated with significant differences in cardiomyocyte apoptosis and anti-inflammatory effects. Thus, in clinical cardiac surgery, inhibition of reperfusion- induced thrombin may offer beneficial effects by mechanisms other than direct anticoagulation. [Copyright &y& Elsevier]

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. [Copyright &y& Elsevier]

Summary: The clinical presentation of myocarditis is highly variable, and histopathology is thus considered to be the cornerstone of diagnosis. We studied how accurately myocarditis was diagnosed in a series of routine autopsies and how fatal myocarditis presents clinically. All death certificates with myocarditis recorded as the underlying cause of death in Finland in 1970 to 1998 were collected retrospectively (N = 639). All cases with cardiac autopsy samples and clinical data available (n = 142; median age, 51 years) were included in this study. The cardiac samples were reexamined for the presence of myocarditis by 3 experienced independent pathologists using the Dallas criteria. The clinical data were evaluated for the presenting signs and symptoms of myocarditis. Histopathologic reanalysis showed that only 32% of the 142 subjects met the Dallas criteria for myocarditis (75% of pediatric and 28% of adult patients, P = .001). Clinicians had suspected myocarditis in only one third of the hospitalized Dallas-positive patients. Dallas-positive patients presented more often with features of myocardial infarction (26% versus 9%, P = .026) or heart failure (35% versus 10%, P = .001) than Dallas-negative subjects. The signs and symptoms of infectious disease were also more common in Dallas-positive patients (61% versus 23%, P < .001). In contrast, Dallas-negative subjects died suddenly or were found dead more frequently (68% versus 39%, P = .004). The most evident cause of death in the Dallas-negative subjects was ischemic heart disease (n = 78, 55% of all cases). Our study provides evidence that myocarditis is overdiagnosed on routine autopsies, particularly in patients who have died suddenly or are found dead. Fatal myocarditis appears to present equally often as heart failure, sudden death, or mimicking myocardial infarction. [Copyright &y& Elsevier]

Acute myocarditis is often a self-limited process with a good outcome. Experimental animal studies have found that cardiomyocyte apoptosis occurs in severe forms of myocarditis. We studied whether cardiomyocyte apoptosis plays a role in the development of fatal acute human myocarditis. Myocardial autopsy samples from subjects who died of acute myocarditis in Finland between 1970 and 1998 were studied. Thirty-three of these cases(16 men and 17 women; 45 ± 6 years old) were randomly selected for this study. All cases fulfilled the histopathologic Dallas criteria for myocarditis. Eight subjects who had died accidentally served as controls. Apoptotic DNA fragmentation (terminal transferase-mediated DNA nick end labeling) and activation of caspase-3 (immunohistochemistry) were detected. The mode of death was determined retrospectively from all available clinical data. In fatal myocarditis, large amounts of cardiomyocytes showed apoptotic DNA fragmentation or contained active caspase-3 (2.0 ± 0.3% and 2.8 ± 0.4%, respectively). In the controls, few apoptotic cardiomyocytes were found (0.008 ± 0.003% by terminal transferase-mediated DNA nick end labeling and 0.009 ± 0.003% by detection of active caspase-3, p <0.001 vs myocarditis). The amount of apoptosis did not correlate with the age or gender of the cases, recognized viral etiology, histologic features, or duration of disease. However, more apoptotic cardiomyocytes were detected in the subjects who had myocarditis and had died of heart failure (n = 18) than in those who had myocarditis and died suddenly of cardiac arrest (n = 15; 2.6 ± 0.4% vs 1.1 ± 0.2%, p <0.001). In conclusion, cardiomyocyte apoptosis is a common mechanism of myocardial damage in severe acute human myocarditis. Moreover, higher rates of cardiomyocyte apoptosis are associated with the development of fatal heart failure in acute myocarditis. [Copyright &y& Elsevier]

: BackgroundThe aim of the present study was to ascertain the percentage of left apical myocardial apoptosis in three-vessel coronary artery bypass grafting patients quantitatively and the impact of ischemic preconditioning.: MethodsTwenty-one patients with three-vessel disease who had elective coronary artery bypass grafting were randomized in a ratio of 2:1 to ischemic preconditioning (n = 14) or a control group (n = 7). The ischemic preconditioning protocol was established by two cycles of ascending aorta occlusion for 2 minutes followed by 3 minutes of reperfusion. Myocardial samples from the apex of the left ventricle were taken using a Tru-Cut needle before aortic cross-clamping and immediately after declamping. The percentage of apoptosis was analyzed by TUNEL methods. Data on hemodynamics and biochemical markers were collected.: ResultsLow levels of myocardial apoptosis were found before the operation (0.01% ± 0.00%). During the early reperfusion period, the percentage of myocardial apoptotic cells significantly increased (0.15% ± 0.05%, p = 0.008). Ischemic preconditioning significantly improved cardiac index and right ventricular ejection fraction recovery after the operation (p = 0.036 and 0.001 respectively, repeated measure) but had no effect on myocardial apoptosis before and after the operation (0.01 ± 0.00 versus 0.01 ± 0.00, p = 0.658 and 0.12% ± 0.04% versus 0.23% ± 0.14%, p = 0.302).: ConclusionsCardioplegic myocardial ischemia during open heart operation was associated with induction of cardiomyocyte apoptosis in humans. Attenuation of postoperative cardiac dysfunction by ischemic preconditioning appeared to be independent of apoptosis. [Copyright &y& Elsevier]

No evidence-based guidelines are available for operative neurosurgical treatment of older patients with traumatic brain injuries (TBIs), and no population-based results of current practice have been reported. The objective of the present study was to investigate the rates of trauma craniotomy operations and later mortality in older adults with TBI in Finland. Nationwide databases were searched for all admissions with a TBI diagnosis and after trauma craniotomy, and later deaths for persons aged ≥60 years from 2004 to 2018. The study period included 2166 patients (64% men; mean age, 70.3 years) who had undergone TBI-related craniotomy. The incidence rate of operations decreased with a concomitant decrease in adjusted mortality (30-day mortality, P < 0.001; 1-year mortality, P < 0.001) and increase in mean patient age (R 2 = 0.005; P < 0.001) during the study period. The cumulative mortality was 25% at 30 days and 38% at 1 year. The comorbidities increasing the hazard for 30-day mortality were diabetes, a history of malignancy, peripheral vascular disease, and a history of myocardial infarction. For 1-year mortality, the comorbidities were heart failure and a history of myocardial infarction. Evacuation of an epidural hematoma decreased the hazard for mortality. In contrast, evacuation of an intracerebral hematoma and decompressive craniectomy increased the risk at both 30 days and 1 year. Among older adults in Finland, the rate of trauma craniotomy and later mortality has been decreasing although the mean age of operated patients has been increasing. This can be expected to be related to an improved understanding of geriatric TBIs and, consequently, improved selection of patients for targeted therapy. [ABSTRACT FROM AUTHOR]

Abstract: High levels of antibodies (Abs) against the C-terminal end of the Trypanosoma cruzi ribosomal P2β protein, defined by the R13 peptide, are detected in sera from patients with chronic Chagas heart disease (cChHD). These Abs can cross-react with the β1-adrenergic receptor (β1-AR), inducing a functional response in cardiomyocytes. In this study, we report that a monoclonal Ab against the R13 peptide, called mAb 17.2, and its single-chain Fv fragment (scFv), C5, caused apoptosis of murine adult cardiac HL-1 cells, and this effect was inhibited by pre-incubation with the β-blocker, propranolol. In addition, apoptosis induced by mAb 17.2 might involve the mitochondrial pathway evidenced by an increase in pro-apoptotic molecule, Bax/anti-apoptotic molecule, BclXL, mRNA levels. HL-1 cells also underwent apoptosis after incubation with nine of 23 IgGs from cChHD patients (39.1%) that presented reactivity against R13 peptide and β1-AR. The apoptotic effect caused by these IgGs was partially abolished by pre-incubation with R13 peptide or propranolol, suggesting the involvement of the C-terminal end of ribosomal P proteins and the β-adrenergic pathway. Moreover, we observed high rates of cardiomyocyte apoptosis in two tissue samples from cChHD patients by using a TUNEL assay and staining of active caspase-3. Our data demonstrate that Abs developed during T. cruzi infection have a strong cardiomyocyte apoptosis inducing ability, which could contribute to the heart disease developed in patients with cChHD. [Copyright &y& Elsevier]

Tissue inhibitor of metalloproteinases 4 (TIMP4) is expressed highly in heart and found dysregulated in human cardiovascular diseases. It controls extracellular matrix remodeling by inhibiting matrix metalloproteinases (MMPs) and is implicated in processes including cell proliferation, apoptosis, and angiogenesis. Timp4-deficient mice (Timp4-/-) were generated to assess TIMP4 function in normal development and in models of heart disease. We deleted exons 1-3 of the Timp4 gene by homologous recombination. Timp4-/- mice are born healthy, develop normally, and produce litters of normal size and gender distribution. These mice show no compensation by overexpression of Timp1, Timp2, or Timp3 in the heart. Following cardiac pressure overload by aortic banding, Timp4-/- mice have comparable survival rate, cardiac histology, and cardiac function to controls. In this case, Timp4 deficiency is compensated by increased cardiac Timp2 expression. Strikingly, the induction of myocardial infarction (MI) leads to significantly increased mortality in Timp4-/- mice primarily due to left ventricular rupture. The post-MI mortality of Timp4-/- mice is reduced by administration of a synthetic MMP inhibitor. Furthermore, combining the genetic deletion of Mmp2 also rescues the higher post-MI mortality of Timp4-/- mice. Finally, Timp4-/- mice suffer reduced cardiac function at 20 months of age. Timp4 is not essential for murine development, although its loss moderately compromises cardiac function with aging. Timp4-/- mice are more susceptible to MI but not to pressure overload, and TIMP4 functions in its capacity as a metalloproteinase inhibitor after myocardial infarction. [ABSTRACT FROM AUTHOR]

Introduction: Viruses are known to induce apoptosis in their host cells. We studied whether cardiomyocyte apoptosis occurs upon coxsackievirus B3 (CVB3) infection and whether virus-associated apoptosis plays a role in the pathogenesis of experimental myocarditis. Methods: BALB/c mice were infected with two variants of CVB3 causing either mild or severe myocarditis. Myocardial and serum samples were collected from Day 1 to Day 14 after virus inoculation. Apoptosis was detected in myocardial tissue sections using the terminal transferase-mediated DNA nick end labelling (TUNEL) assay and staining of active caspase 3, and compared with the presence of infectious CVB3 and viral proteins in cardiomyocytes. Results: Compared with the noninfected control mice, infection with either CVB3 variant resulted in significantly increased cardiomyocyte apoptosis, which peaked on Day 5 after infection. At this time, the average percentages of apoptotic cardiomyocytes were 0.17% (SD 0.04; P=.03) and 0.77% (SD 0.11; P<.01) in mild and severe disease forms, respectively. The amount of apoptosis correlated with titers of infectious CVB3 in the heart muscle. Viral proteins were detected in the TUNEL-positive cells by immunohistochemistry. In the late stages of disease, apoptosis, together with inflammatory infiltrates persisted only in the severe disease form. Conclusions: CVB3-associated myocardial damage involves cardiomyocyte apoptosis. In the early stages of the disease, it appears to be triggered by viral replication in the cardiomyocytes. [Copyright &y& Elsevier]