Impact of the Main Cardiovascular Risk Factors on Plasma Extracellular Vesicles and Their Influence on the Heart's Vulnerability to Ischemia-Reperfusion Injury.

The majority of cardiovascular deaths are associated with acute coronary syndrome, especially ST-elevation myocardial infarction. Therapeutic reperfusion alone can contribute up to 40 percent of total infarct size following coronary artery occlusion, which is called ischemia-reperfusion injury (IRI). Its size depends on many factors, including the main risk factors of cardiovascular mortality, such as age, sex, systolic blood pressure, smoking, and total cholesterol level as well as obesity, diabetes, and physical effort. Extracellular vesicles (EVs) are membrane-coated particles released by every type of cell, which can carry content that affects the functioning of other tissues. Their role is essential in the communication between healthy and dysfunctional cells. In this article, data on the variability of the content of EVs in patients with the most prevalent cardiovascular risk factors is presented, and their influence on IRI is discussed.

Associations Between Preoperative Glucose and Hemoglobin A1c Level and Myocardial Injury After Noncardiac Surgery.

Background Perioperative blood glucose level has shown an association with postoperative outcomes. We compared the incidences of myocardial injury after noncardiac surgery (MINS) and 30-day mortality, according to preoperative blood glucose and hemoglobin A1c (HbA1c) levels. Methods and Results The patients were divided according to blood glucose level within 1 day before surgery. The hyperglycemia group was defined with fasting glucose >140 mg/dL or random glucose >180 mg/dL. In addition, we compared the outcomes according to HbA1c >6.5% among patients with available HbA1c within 3 months before surgery. The primary outcome was MINS, and 30-day mortality was also compared. A total of 12 304 patients were enrolled and divided into 2 groups: 8324 (67.7%) in the normal group and 3980 (32.3%) in the hyperglycemia group. After adjustment with inverse probability of weighting, the hyperglycemia group exhibited significantly higher incidences of MINS and 30-day mortality (18.7% versus 27.6%; odds ratio, 1.29; 95% CI, 1.18-1.42; P<0.001; and 2.0% versus 5.1%; hazard ratio, 2.00; 95% CI, 1.61-2.49; P<0.001, respectively). In contrast to blood glucose, HbA1c was not associated with MINS or 30-day mortality. Conclusions Preoperative hyperglycemia was associated with MINS and 30-day mortality, whereas HbA1c was not. Immediate glucose control may be more crucial than long-term glucose control in patients undergoing noncardiac surgery. Registration URL: https://www.cris.nih.go.kr; Unique identifier: KCT0004244.

Editor's Choice- Pathophysiology and therapy of myocardial ischaemia/reperfusion syndrome.

There is a need to find interventions able to reduce the extent of injury in reperfused ST-segment elevation myocardial infarction (STEMI) beyond timely reperfusion. In this review, we summarise the clinical impact of STEMI from epidemiological, clinical and biological perspectives. We also revise the pathophysiology underlying the ischaemia/reperfusion syndrome occurring in reperfused STEMI, including the several players involved in this syndrome, such as cardiomyocytes, microcirculation and circulating cells. Interventions aimed to reduce the resultant infarct size, known as cardioprotective therapies, are extensively discussed, putting the focus on both mechanical interventions (i.e. ischaemic conditioning) and promising pharmacological therapies, such as early intravenous metoprolol, exenatide and other glucose modulators, N-acetylcysteine as well as on some other classic therapies which have failed to be translated to the clinical arena. Novel targets for evolving therapeutic interventions to ameliorate ischaemia/reperfusion injury are also discussed. Finally, we highlight the necessity to improve the study design of future randomised clinical trials in the field, as well as to select patients better who can most likely benefit from cardioprotective interventions.

Blood cardioplegia benefits only patients with a long cross-clamp time.

INTRODUCTION: A clear advantage of blood versus crystalloid cardioplegia has not yet been observed in smaller population studies. The purpose of this article was to further investigate the clinical outcomes of blood versus crystalloid cardioplegia in a large propensity-matched cohort of patients who underwent cardiac surgery. METHODS: The study was a single-centre study. Data was withdrawn from the Western Denmark Heart Registry, which comprises a perfusion section for each procedure. A total of 4,852 patients were propensity matched into crystalloid (CC) vs blood cardioplegia (BC) groups. The primary end points were creatinine kinase-MB (CKMB) elevation, acute myocardial infarction (AMI), stroke, dialysis, coronary angiography (CAG) and mortality (30 days and 6 months). RESULTS: We found lower odds ratio in 30-day mortality in the BC group (OR 0.21; CI 0.06-0.68), but no difference in overall 6-month mortality. There was no difference in CKMB elevation, AMI, dialysis or stroke. Several end points were further analysed for different cross-clamp times. In the CC group, ventilation time above 600 minutes was seen more often in almost all cross-clamp time intervals (23.5 % vs 12.2 %; p<0.0001; χ2-test) and 6-month mortality was significantly higher when the cross-clamp time exceeded 210 minutes (64.3 vs 23.8; p=0.018; χ2-test). CONCLUSIONS: We did not find clear evidence of superiority of either type in the uncomplicated patient. When prolonged cross-clamp time or postoperative ventilation is expected, this study indicates that blood cardioplegia might be preferable.

RIPHeart (Remote Ischemic Preconditioning for Heart Surgery) Study: Myocardial Dysfunction, Postoperative Neurocognitive Dysfunction, and 1 Year Follow-Up.

BACKGROUND: Remote ischemic preconditioning (RIPC) has been suggested to protect against certain forms of organ injury after cardiac surgery. Previously, we reported the main results of RIPHeart (Remote Ischemic Preconditioning for Heart Surgery) Study, a multicenter trial randomizing 1403 cardiac surgery patients receiving either RIPC or sham-RIPC. METHODS AND RESULTS: In this follow-up paper, we present 1-year follow-up of the composite primary end point and its individual components (all-cause mortality, myocardial infarction, stroke and acute renal failure), in a sub-group of patients, intraoperative myocardial dysfunction assessed by transesophageal echocardiography and the incidence of postoperative neurocognitive dysfunction 5 to 7 days and 3 months after surgery. RIPC neither showed any beneficial effect on the 1-year composite primary end point (RIPC versus sham-RIPC 16.4% versus 16.9%) and its individual components (all-cause mortality [3.4% versus 2.5%], myocardial infarction [7.0% versus 9.4%], stroke [2.2% versus 3.1%], acute renal failure [7.0% versus 5.7%]) nor improved intraoperative myocardial dysfunction or incidence of postoperative neurocognitive dysfunction 5 to 7 days (67 [47.5%] versus 71 [53.8%] patients) and 3 months after surgery (17 [27.9%] versus 18 [27.7%] patients), respectively. CONCLUSIONS: Similar to our main study, RIPC had no effect on intraoperative myocardial dysfunction, neurocognitive function and long-term outcome in cardiac surgery patients undergoing propofol anesthesia. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01067703.

Daytime variation of perioperative myocardial injury in cardiac surgery and its prevention by Rev-Erbα antagonism: a single-centre propensity-matched cohort study and a randomised study.

BACKGROUND: On-pump cardiac surgery provokes a predictable perioperative myocardial ischaemia-reperfusion injury which is associated with poor clinical outcomes. We determined the occurrence of time-of-the-day variation in perioperative myocardial injury in patients undergoing aortic valve replacement and its molecular mechanisms. METHODS: We studied the incidence of major adverse cardiac events in a prospective observational single-centre cohort study of patients with severe aortic stenosis and preserved left ventricular ejection fraction (>50%) who were referred to our cardiovascular surgery department at Lille University Hospital (Lille, France) for aortic valve replacement and underwent surgery in the morning or afternoon. Patients were matched into pairs by propensity score. We also did a randomised study, in which we evaluated perioperative myocardial injury and myocardial samples of patients randomly assigned (1:1) via permuted block randomisation (block size of eight) to undergo isolated aortic valve replacement surgery either in the morning or afternoon. We also evaluated human and rodent myocardium in ex-vivo hypoxia-reoxygenation models and did a transcriptomic analysis in myocardial samples from the randomised patients to identify the signalling pathway(s) involved. The primary objective of the study was to assess whether myocardial tolerance of ischaemia-reperfusion differed depending on the timing of aortic valve replacement surgery (morning vs afternoon), as measured by the occurrence of major adverse cardiovascular events (cardiovascular death, myocardial infarction, and admission to hospital for acute heart failure). The randomised study is registered with ClinicalTrials.gov, number NCT02812901. FINDINGS: In the cohort study (n=596 patients in matched pairs who underwent either morning surgery [n=298] or afternoon surgery [n=298]), during the 500 days following aortic valve replacement, the incidence of major adverse cardiac events was lower in the afternoon surgery group than in the morning group: hazard ratio 0·50 (95% CI 0·32-0·77; p=0·0021). In the randomised study, 88 patients were randomly assigned to undergo surgery in the morning (n=44) or afternoon (n=44); perioperative myocardial injury assessed with the geometric mean of perioperative cardiac troponin T release was significantly lower in the afternoon group than in the morning group (estimated ratio of geometric means for afternoon to morning of 0·79 [95% CI 0·68-0·93; p=0·0045]). Ex-vivo analysis of human myocardium revealed an intrinsic morning-afternoon variation in hypoxia-reoxygenation tolerance, concomitant with transcriptional alterations in circadian gene expression with the nuclear receptor Rev-Erbα being highest in the morning. In a mouse Langendorff model of hypoxia-reoxygenation myocardial injury, Rev-Erbα gene deletion or antagonist treatment reduced injury at the time of sleep-to-wake transition, through an increase in the expression of the ischaemia-reperfusion injury modulator CDKN1a/p21. INTERPRETATION: Perioperative myocardial injury is transcriptionally orchestrated by the circadian clock in patients undergoing aortic valve replacement, and Rev-Erbα antagonism seems to be a pharmacological strategy for cardioprotection. Afternoon surgery might provide perioperative myocardial protection and lead to improved patient outcomes compared with morning surgery. FUNDING: Fondation de France, Fédération Française de Cardiologie, EU-FP7-Eurhythdia, Agence Nationale pour la Recherche ANR-10-LABX-46, and CPER-Centre Transdisciplinaire de Recherche sur la Longévité.

Effect of Remote Ischemic Preconditioning on Outcomes in Adult Cardiac Surgery: A Systematic Review and Meta-analysis of Randomized Controlled Studies.

BACKGROUND: Remote ischemic preconditioning (RIPC) has been demonstrated to prevent organ dysfunction in cardiac surgery patients. However, recent large, prospective, multicenter, randomized controlled trials (RCTs) had controversial results. Thus, a meta-analysis of RCTs was performed to investigate whether RIPC can reduce the incidence of acute myocardial infarction (AMI), acute kidney injury (AKI), and mortality in adult cardiac surgery patients. METHODS: Study data were collected from Medline, Elsevier, Cochrane Central Register of Controlled Trials and Web of Science databases. RCTs involving the effect of RIPC on organ protection in cardiac surgery patients, which reported the concentration or total release of creatine kinase-myocardial band, troponin I/troponin T (TNI/TNT) after operation, or the incidence of AMI, AKI, or mortality, were selected. Two reviewers independently extracted data using a standardized data extraction protocol where TNI or TNT concentrations; total TNI released after cardiac surgery; and the incidence of AKI, AMI, and mortality were recorded. Review Manager 5.3 software was used to analyze the data. RESULTS: Thirty trials, including 7036 patients were included in the analyses. RIPC significantly decreased the concentration of TNI/TNT (standard mean difference [SMD], -0.25 ng/mL; 95% confidence interval [CI], -0.41 to -0.048 ng/mL; P = .004), creatine kinase-myocardial band (SMD, -0.22; 95% CI, -0.07-0.35 ng/mL; P = .46), and the total TNI/TNT release (SMD, -0.49 ng/mL; 95% CI, -0.93 to -0.55 ng/mL; P = .03) in cardiac surgery patients after a procedure. However, RIPC could not reduce the incidence of AMI (relative risk, 0.89; 95% CI, 0.70-1.13; P = .34) and AKI (relative risk, 0.88; 95% CI, 0.72-1.06; P = .18), and there was also no effect of RIPC on mortality in adult cardiac surgery patients. Interestingly, subgroup analysis showed that RIPC reduced incidence of AKI and mortality of cardiac surgery patients who received volatile agent anesthesia. CONCLUSIONS: Our meta-analysis demonstrated that RIPC reduced TNI/TNT release after cardiac surgery. RIPC did not significantly reduce the incidence of AKI, AMI, and mortality. However, RIPC could reduce mortality in patients receiving volatile inhalational agent anesthesia.

Effects of prostaglandin E1 on reperfusion injury patients: A meta-analysis of randomized controlled trials.

BACKGROUND: Prostaglandin E1 (PGE1) is widely used as a pretreatment for myocardial reperfusion injury in animal experiments. However, the cardioprotective effects of PGE1 in patients have not been established. We performed a meta-analysis to investigate whether PGE1 is cardioprotective, based on the reduction of correlative reperfusion injury events (CRIE), major adverse cardiac events (MACE), and biomarker release in patients with ischemia reperfusion injury. METHODS: The Medline, EMBASE, and Cochrane databases were searched for randomized clinical trials confirming the effects of PGE1. Two investigators independently selected suitable trials, assessed trial quality, and extracted data. RESULTS: Six studies in patients undergoing percutaneous coronary intervention (4 studies) and cardiac surgery (2 studies), comprising a total of 445 patients, were included in this review. The results showed that PGE1 reduced the incidence of CRIE (relative ratio 0.4 [95% confidence interval 0.43, 0.95]), the incidence of MACE (0.35 [0.17, 0.70]), and the level of troponin T (standardized mean difference 20.28 [20.47, 20.09]), creatine kinase-MB (-1.74 [-3.21, - 0.27]), interleukin-6 (-1.37 [-2.69, - 0.04]), and interleukin-8 (-2.05 [-2.75, - 1.34]). CONCLUSION: PGE1 may have beneficial effects on myocardial reperfusion injury in the clinic.

Comparison of high glucose concentration blood and crystalloid cardioplegia in paediatric cardiac surgery: a randomized clinical trial.

OBJECTIVES: This study investigates the effects of high glucose content on patients undergoing cold crystalloid versus cold blood cardioplegia in terms of early clinical results, functional myocardial recovery and ischaemia-reperfusion injury in patients undergoing repair of acyanotic cardiac lesions. METHODS: Patients were randomly assigned to receive either crystalloid (n = 31) or blood cardioplegia (n = 31). Early clinical results were assessed. Changes in left ventricular fractional shortening, arterial blood lactate levels, central venous saturation, cardiac Troponin I release and blood glucose concentration were measured during the first 24 h after ischaemia. RESULTS: There was no significant difference in clinical outcomes and postoperative complication rates between groups. The postoperative changes in left ventricular function, lactate levels, central venous saturation and Troponin I were not significantly different between groups. The use of crystalloid cardioplegia was associated with significant increases in serum glucose compared with blood cardioplegia. CONCLUSIONS: A high glucose content blood cardioplegia does not show any advantage compared with crystalloid cardioplegia in terms of clinical outcomes, functional recovery and the degree of ischaemic injury in infants and children undergoing repair of acyanotic heart lesions. High glucose concentration of the cardioplegic solution might potentiate ischaemia-reperfusion injury and diminish the beneficial effects of blood cardioplegia.

Comparison of the efficacy of the cardiac hypothermia and normothermia to myocardial damage in coronary artery bypass graft surgery with systemic normothermic cardiopulmonary bypass.

AIM: The aim of our research is to investigate the cardiac damage formed by either local cardiac hypothermia or cardiac normothermia technique in patients who undergone isolated coronary artery bypass graft (CABG) surgery. METHODS: The total of 40 patients who underwent isolated CABG operation under normothermic cardiopulmonary bypass (CPB) were studied. Patients were randomly divided into two groups as cardiac hypothermia and cardiac normothermia. Myocardial temperature was measured from the interventricular septum before aortic cross-clamp (ACC) (baseline), the ACC 20th minutes (ischemia) and after 20 minutes removal of the ACC (reperfusion). The coronary sinus blood samples were simultaneously obtained from the retrograde cardioplegia cannula while myocardial temperature was being measured. Complement component 3 (C3), complement component 4 (C4), troponin I and tumor necrosis factor-alpha (TNF-α) was measured from the coronary sinus blood samples. RESULTS: Myocardial temperature was between 18-28 °C (deep hypothermia) during ACC in group 1. Myocardial temperature was over 34 °C (normothermia) during ACC in group 2. TNF-α values of group 1 for ischemia and reperfusion were higher than group 2, and it was found statistically significant (P<0.05). CONCLUSION: Myocardial damage was less than in normothermia group according to hypothermia group. The results show that ice-cold blood cardioplegia and local ice treatment of the heart during CPB seems to harm the heart more than warm blood cardioplegia.

Diabetic inhibition of preconditioning- and postconditioning-mediated myocardial protection against ischemia/reperfusion injury.

Ischemic preconditioning (IPC) or postconditioning (Ipost) is proved to efficiently prevent ischemia/reperfusion injuries. Mortality of diabetic patients with acute myocardial infarction was found to be 2-6 folds higher than that of non-diabetic patients with same myocardial infarction, which may be in part due to diabetic inhibition of IPC- and Ipost-mediated protective mechanisms. Both IPC- and Ipost-mediated myocardial protection is predominantly mediated by stimulating PI3K/Akt and associated GSK-3ß pathway while diabetes-mediated pathogenic effects are found to be mediated by inhibiting PI3K/Akt and associated GSK-3ß pathway. Therefore, this review briefly introduced the general features of IPC- and Ipost-mediated myocardial protection and the general pathogenic effects of diabetes on the myocardium. We have collected experimental evidence that indicates the diabetic inhibition of IPC- and Ipost-mediated myocardial protection. Increasing evidence implies that diabetic inhibition of IPC- and Ipost-mediated myocardial protection may be mediated by inhibiting PI3K/Akt and associated GSK-3ß pathway. Therefore any strategy to activate PI3K/Akt and associated GSK-3ß pathway to release the diabetic inhibition of both IPC and Ipost-mediated myocardial protection may provide the protective effect against ischemia/reperfusion injuries.

Clinically useful cardioprotection: ischemic preconditioning then and now.

Ischemic preconditioning (IP) is the most effective, reproducible form of protection against myocardial cell death yet described. The mechanism of classic IP has not been identified, but recent investigations have focused on the mitochondrial permeability transition pore (mPTP). Similarly, the mechanism of the "second window of protection" (SWOP) is not known but thought to involve increased expression of important gene products. Currently, IP in the clinical arena is limited to cardiac surgery, planned angioplasty, and organ preservation protocols. To move preconditioning into a broader clinical arena will require resolution of important fundamental yet stubborn problems involving both basic and clinical science. Important unresolved issues include the mechanisms involved in the transition from reversible to irreversible injury, the amount of potential salvageable myocardium present at the onset of reperfusion, the identity and signaling of the mPTP, the optimization of protocols, the identity of end effectors (SWOP), and the identification of the best experimental model systems. From a clinical standpoint, important issues include the influence of comorbidities on cardioprotection, identification of appropriate animal models, the lack of a biologic marker of the cardioprotective state, the influence of coexistent therapeutic drugs, potential toxicity of pharmacologic mimics, and the window of opportunity for significant protection. Ischemic preconditioning has yielded promising results in other organs including the brain as well as tissue preservation for certain surgical procedures that will require definition of the underlying mechanism(s) to be fully exploited clinically. Over the past 25 years, the scientific community has learned much regarding the biology and potential mechanisms of IP and the concept has been expanded to many other organ systems in many other clinically relevant scenarios. To realize the full clinical potential will require continued investigation into the mechanism.

Recombinant human erythropoietin pretreatment attenuates heart ischemia-reperfusion injury in rats by suppressing the systemic inflammatory response.

BACKGROUND: Ischemia-reperfusion (I/R) injury may influence graft function after transplantation. Erythropoietin (EPO) attenuates I/R injury in various animal organs such as intestine, brain, and kidney. OBJECTIVE: To evaluate the effects of pretreatment with recombinant human EPO (rhEPO) on I/R-induced heart injury. MATERIALS AND METHODS: A rat model of I/R injury was established by ligating the left descending coronary artery for 30 minutes, followed by reperfusion for 4 hours. Fifty Sprague-Dawley rats were divided into 5 groups: sham operation; I/R; I/R+rhEPO, 100 U/kg; I/R+rhEPO, 1000 U/kg; and I/R+rhEPO, 5000 U/kg. Electrocardiograms were assessed continuously to note arrhythmia caused by reperfusion. Serum concentrations of interleukin (IL)-6 and IL-8, and tumor necrosis factor-alpha were measured at 2 and 4 hours after reperfusion. RESULTS: The rhEPO-treated animals exhibited dosage-dependent significant reduction in the incidence of ventricular arrhythmia caused by reperfusion, and markedly decreased serum concentrations of IL-6, IL-8, and tumor necrosis factor-alpha (P < .05) compared with the I/R group (P < .05). CONCLUSION: The rhEPO attenuates myocardial I/R injury in rats, at least in part related to inhibition of the system inflammatory response.

Postischemia myocardial injury in coronary artery bypass patients (PP6).

PURPOSE: To investigate the reperfusion injury of the myocardium in patients undergoing elective coronary artery bypass surgery (CABG) with cardiopulmonary bypass (CPB), we monitored the blood levels of troponin I (TNI), white blood cells, oxygen radicals, malondialdehyde, and myeloperoxidase seeking to define the relationship between the CABG-induced systemic inflammation and myocardial injury. MATERIALS AND METHODS: We selected 10 patients undergoing primary CABG with CPB at moderate hypothermia and cardioplegic arrest concomitant with intermittent warm blood cardioplegia. We compared all data with their own baseline values to study the reperfusion injury. After release of the aortic clamp, blood was drawn from the coronary sinus, via a catheter placed through the right atrium. We measured plasma levels of inflammatory mediators, such as malondialdehyde, myeloperoxidase, oxygen radicals, and the myocardium injury parameter of TNI. RESULTS: Patients showed no difference concerning aortic clamp time. TNI increased significantly at 1, 15, and 30 minutes after the onset of reperfusion. Blood levels of white blood cells, oxygen radicals, malondialdehyde, and myeloperoxidase also increased significantly with reperfusion time. CONCLUSIONS: Reperfusion of ischemic myocardium induced increased TNI, which may be related to the systemic inflammatory responses induced by ischemia and reperfusion of the myocardium among patients undergoing elective coronary bypass surgery.

Apoptosis and cardiopulmonary bypass.

AIM: The aim of this study was to ascertain the percentage of apoptotic myocytes in patients who underwent coronary artery bypass surgery. Apoptotic index (AI) obtained with in situ terminal deoxynucleotidyl transferase-labeled dUTP nick end labeling (TUNEL) method and Bak protein expression were compared. PATIENTS AND METHODS: Twenty consecutive patients who underwent coronary artery bypass surgery, myocardial samples from the right atrium were taken in three stages: before cannulation (the first sample group), after declamping (the second sample group), and 20 minutes after reperfusion (the third sample group). The percentage of apoptotic cells was determined by TUNEL method. Expression of Bak protein was immunohistochemically analyzed. Intermittent ischemia and moderate hypothermia were used as methods of myocardial management during surgery. A statistical analysis was performed by using the Friedman ANOVA analysis of variances, the Kendall coefficient of concordance and the Wilcoxon matched pair test. RESULTS: In the first sample group mean value of Bak expression was 2.61 +/- 2.18, compared with AI 5.38 +/- 3.58, after declamping (the second sample group) the mean value of Bak expression was 4.31 +/- 2.68 while AI was 7.63 +/- 4.38 and after 20 minutes of reperfusion in the third sample group mean value of Bak expression was 8.89 +/- 4.45, while AI was 15.6 +/- 8.45. When compared by using Wilcoxon matched pair test two methods significantly correlated, p > 0.0001. CONCLUSION: The positive correlation between AI obtained by TUNEL method and expression of Bak protein may suggest that apoptosis is activated mainly through mitochondrial activation pathway in ischemic reperfusion injury. The results suggest that ischemic reperfusion injury increases the AI in the right atrial tissue. If so, immunohistochemical expression of Bak protein could be used as a marker of myocardial ischemia induced injury.

The impact of unrepaired versus repaired mitral regurgitation on functional status of patients with ischemic cardiomyopathy at one year after coronary artery bypass grafting.

BACKGROUND AND AIM OF THE STUDY: The issues regarding the appropriate management of patients with ischemic mitral regurgitation (MR) and advanced left ventricular (LV) dysfunction are controversial and limited. The present study was undertaken to evaluate the mid-term dynamics of MR, LV dimensions, function and NYHA functional class in patients with ischemic cardiomyopathy (ICM) and MR who underwent coronary artery bypass grafting (CABG) either alone or combined with mitral valve (MV) repair. METHODS: A total of 199 patients with LV ejection fraction (LVEF) <35% were included in the study. Of these patients, 73 had MR grade 2+ (group 1), 66 had 0 or 1+ MR (group 2) and underwent isolated CABG, and 60 had MR > 2+ and underwent CABG with MV repair (group 3). RESULTS: At one year after surgery, the severity of MR was unchanged from preoperative grade in group 1 (2.1 +/- 0.5 vs. 1.97 +/- 0.8), and increased in group (0.76 +/- 0.43 vs. 1.44 +/- 0.77; p < 0.05), but was significantly lower in group (2.8 +/- 0.5 vs. 1.6 +/- 0.7; p <0.05). In group 1, the LV end-systolic volume index (LVESVI) tended to increase, the LV end-diastolic volume index (LVEDVI) increased from 69.6 +/- 22.6 to 79.6 +/- 23.2 ml/m2 with an increase in LVEF (from 27.9 +/- 5.9 to 31.3 +/- 9.4%), and pulmonary artery pressure (PAP) increased from 31.9 +/- 7.0 to 39.5 +/- 17.4 mmHg. In group 2, the LV volumes tended to increase, LVEF increased from 30. 3 +/- 4.1 to 34.9 +/- 9.1%, and PAP remained unchanged. In group 3, the LVESVI decreased from 55.4 +/- 16.9 to 47.1 +/- 21.7 ml/m2, LVED-VI tended to decrease, LVEF increased from 31.4 +/- 8.6 to 36.5 +/- 11.3%, and PAP decreased from 35.5 +/- 6.0 to 32.8 +/- 8.3 mmHg. CONCLUSION: Isolated CABG in patients with ICM had no favorable effect on MR reduction, and did not prevent its development. MR grade 2+ in patients with ICM at one year after isolated CABG had a deleterious effect on LV functional status, with progression of LV dilatation and increased PAP. A significant reduction or elimination of MR after combined surgery had a marked positive impact on reverse LV remodeling, including regression of LV dilatation, an increased LVEF, and decreased PAP.

Percutaneous coronary intervention in patients with end-stage renal disease.

Patients with end-stage renal disease (ESRD) represent a growing number of patients in the cardiac catheterization laboratories worldwide. This is a consequence of the growing absolute number of ESRD patients in developed countries, better noninvasive diagnostic tools, better catheterization facilities and last-but-not-least better education of referring physicians about the incidence and prognosis of coronary artery disease (CAD) for patients with ESRD. There is growing evidence of the positive impact of coronary revascularization on long-term outcome of these patients. ESRD patients have a high comorbidity and are therefore better candidates for the less invasive approach using percutaneous coronary intervention (PCI) rather than coronary artery bypass surgery (CABG). From the view of the interventional cardiologist, ESRD patients represent one of the most challenging patient cohort concerning technical challenges and potential risk of complication for the patient. Percutaneous coronary intervention (PCI) including debulking techniques and stent implantation is the current standard therapy for patients with symptomatic single-vessel disease (SVD) and the preferred therapy for most patients with focal, polyfocal or even diffuse multi-vessel disease (MVD). Coronary bypass surgery is reserved for a decreasing number of patients with mechanically untreatable coronary lesions and unprotected left main stem stenosis. The problem of restenosis and subsequent target lesion revascularization has been decreased to a minimum by the use of drug-eluting stents (DES), even though prospective randomized trials including ESRD patients are lacking. In case of acute coronary syndromes, the need for immediate coronary angiography and subsequent revascularization by means of PCI should be pointed out.

The salvage potential of coronary sinus interventions: meta-analysis and pathophysiologic consequences.

OBJECTIVES: Intermittent coronary sinus occlusion has been described to be effective in salvaging ischemic myocardium. This meta-analysis aims to review the efficacy of intermittent coronary sinus occlusion and intermittent coronary sinus occlusion in combination with retroperfusion of arterial blood as methods of myocardial salvage. METHODS: A Medline search was performed to review the published literature on intermittent coronary sinus occlusion. The study inclusion criterion was a randomized, placebo-controlled trial with area of infarction (expressed as a percentage of the area at risk) as the primary end point. RESULTS: Seven experimental trials comprising 125 test animals were found that analyzed the effects of intermittent coronary sinus occlusion on ischemic damage during coronary occlusion. A further 5 studies comprising 88 animals were designed to evaluate the effect of intermittent coronary sinus occlusion in combination with retroperfusion of arterial blood on the infarct size. A meta-analysis of the 7 studies analyzing the effect of intermittent coronary sinus occlusion revealed a significant reduction in infarct size of 29.3% in the treatment group compared with that in the placebo group (P <.001; 95% confidence interval, -40.9 to -17.7). A meta-analysis of the 5 trials analyzing the effect of intermittent coronary sinus occlusion in combination with retroperfusion revealed a reduction in infarct size of 39.4% in the treatment group compared with that in the placebo group (P <.001; 95% confidence interval, -48.9 to -29.9). Comparison between intermittent coronary sinus occlusion and intermittent coronary sinus occlusion in combination with retroperfusion of arterial blood showed no statistical difference (P =.19). An inverse relationship between achieved coronary sinus pressure increase per minute and infarct size could be found in the intermittent coronary sinus occlusion group (r = -0.92; P <.007), whereas in combination with retroperfusion, there was a negative correlation both between achieved coronary sinus pressure and the amount of the retroperfusate and myocardial salvage (r = -0.97; P <.004). CONCLUSIONS: The use of intermittent coronary sinus occlusion and intermittent coronary sinus occlusion in combination with retroperfusion of arterial blood significantly decreases ischemic damage during coronary occlusions. Intermittent coronary sinus occlusion in combination with retroperfusion exhibits no significant profit in salvaging the ischemic myocardium in comparison with that provided by intermittent coronary sinus occlusion alone.

Blood versus crystalloid cardioplegia for myocardial protection of donor hearts during transplantation: A prospective, randomized clinical trial.

OBJECTIVE: To assess the safety and efficacy of myocardial protection of the donor heart during transplantation with the use of blood cardioplegia, a prospective randomized clinical trial was undertaken between January 1997 and March 1998. METHODS: Forty-seven consecutive patients were assigned either to crystalloid (27 patients; group 1) or blood cardioplegia (20 patients; group 2). Comparison of recipient age (54 +/- 11 years vs 55 +/- 7 years; P =. 9), sex (89% vs 90% male patients; P =.9), diagnosis (63% vs 65% dilated cardiomyopathy; P =.8), elevated pulmonary vascular resistance (30% vs 30%; P =.9), prior cardiac operations (22% vs 30%; P =.5), need for urgent heart transplantation (7% vs 20%; P =. 2), donor age (32 +/- 11 years vs 31 +/- 13 years; P =.7), cause of death (33% vs 40% vascular; P =.5), and global myocardial ischemia (176 +/- 51 minutes vs 180 +/- 58 minutes; P =.5) showed no difference. Hemodynamically unstable donors (15% vs 45%; P =.02) were more prevalent in group 2. RESULTS: Operative mortality rates (4% vs 5%; P =.8), high-dose inotropic support (41% vs 30%; P = 0.6), and postoperative mechanical assistance (11% vs 10%; P = 0.9) were comparable in the 2 groups. Prevalence of acute right heart failure (27% vs 0; P =.02) and of temporary complete atrioventricular block (52% vs 20%; P =.02) were greater in group 1. Spontaneous sinus rhythm recovery was more prevalent in group 2 (11% vs 40%; P =.02). Higher peak creatine kinase (1429 +/- 725 u/L vs 868 +/- 466 u/L; P =.01) and creatine kinase MB (144 +/- 90 u/L vs 102 +/- 59 u/L; P =. 06) levels suggested more severe ischemic injury in group I. CONCLUSION: Use of blood cardioplegia was associated with a lower prevalence of right heart failure, cardiac rhythm dysfunction, and laboratory evidence of ischemia.

Gender and acute myocardial infarction: is there a different response to thrombolysis?

OBJECTIVES: This study sought to 1) determine the effect of gender on early and late infarct-related artery patency and reocclusion after thrombolytic therapy for acute myocardial infarction; 2) examine the effect of gender on left ventricular function in response to injury/reperfusion; and 3) assess the independent contribution of gender to early (30-day) mortality after acute myocardial infarction. BACKGROUND: Women have a higher mortality rate than men after myocardial infarction. However, the effect of gender on infarct-related coronary artery patency and left ventricular response to injury/reperfusion have not been fully defined in the thrombolytic era. METHODS: Patency rates and global and regional left ventricular function were determined in patients at 90 min and 5 to 7 days after thrombolytic therapy for acute myocardial infarction. The effect of gender on infarct-related artery patency and left ventricular function was determined. Thirty-day mortality differences between women and men were compared. RESULTS: Women were significantly older and had more hypertension, diabetes, hypercholesterolemia, heart failure and shock. They were less likely to have had a previous myocardial infarction, history of smoking or previous bypass surgery. Ninety-minute patency rates (Thrombolysis in Myocardial Infarction [TIMI] flow grade 3) in women and men were 39% and 38%, respectively (p = 0.5). Reocclusion rates were 8.7% in women versus 5.1% in men (p = 0.14). Women had more recurrent ischemia than men (21.4% vs. 17.0%, respectively, p = 0.01). Ninety-minute ejection fraction and regional ventricular function were clinically similar in women and men with TIMI 2 or 3 flow (ejection fraction [mean +/- SD]: 63.4 +/- 6% vs. 59.4 +/- 0.7%, p = 0.02; number of chords: 21.4 +/- 0.9 vs. 21.0 +/- 1.9, p = 0.7; SD/chord: -2.4 +/- 08 vs. -2.4 +/- 0.2, p = 0.9, respectively). No clinically significant differences in left ventricular function were noted at 5- to 7-day follow-up. Women had a greater hyperkinetic response than men in the noninfarct zone (SD/chord: 2.4 +/- 0.2 vs. 1.7 +/- 0.1, p = 0.005). The 30-day mortality rate was 13.1% in women versus 4.8% in men (p < or = 0.0001). After adjustment for other clinical and angiographic variables, gender remained an independent determinant of 30-day mortality. CONCLUSIONS: Women do not differ significantly from men with regard to either early infarct-related artery patency rates or reocclusion after thrombolytic therapy or ventricular functional response to injury/reperfusion. Gender was an independent determinant of 30-day mortality after acute myocardial infarction.