Objectives: We assessed the effect of milrinone application timing after reperfusion against myocardial stunning as compared with levosimendan in swine. Furthermore, we examined the role of p38 mitogen-activated protein kinase (p38 MAPK) in the milrinone-induced cardioprotection.
Design: All swine were subjected to 12-minutes ischemia followed by 90-minutes reperfusion to generate stunned myocardium. Milrinone or levosimendan was administered intravenously either for 20 minutes starting just after reperfusion or for 70 minutes starting 20 minutes after reperfusion. In another group, SB203580, a selective p38 MAPK inhibitor, was administered with and without milrinone. Regional myocardial contractility was assessed by percent segment shortening (%SS).
Results: Milrinone starting just after reperfusion, but not starting 20 minutes after reperfusion, improved %SS at 30, 60, and 90 minutes after reperfusion compared with that in the control group. SB203580 abolished the beneficial effect of milrinone. On the other hand, levosimendan starting 20 minutes after reperfusion, but not for 20 minutes starting just after reperfusion, improved %SS at 60 and 90 minutes after reperfusion.
Conclusions: Milrinone should be administered just after reperfusion to protect myocardial stunning through p38 MAPK, whereas levosimendan improvement of contractile function could be mainly dependent on its positive inotropic effect.
Objectives: The predictive value of preoperative N-terminal pro-B-type natriuretic peptide (NT-proBNP) was evaluated in patients with acute coronary syndrome undergoing coronary artery bypass grafting (CABG).
Design: As a substudy to a clinical trial 383 patients with acute coronary syndrome undergoing CABG were studied. 17 patients had a concomitant procedure. NT-proBNP was measured immediately preoperatively and evaluated with regard to in-hospital mortality, and severe circulatory failure postoperatively according to prespecified criteria. Follow-up was 3.2 ± 0.9 years.
Results: In patients with isolated CABG, receiver operating characteristics (ROC) analysis showed an area under the curve (AUC) of 0.82 for in-hospital mortality and 0.87 for severe circulatory failure respectively with a best cut-off for preoperative NT-proBNP of 1028 ng/L. This cut-off level independently predicted severe circulatory failure. Patients with NT-proBNP < 1028 ng/L had significantly better long-term survival (p = 0.004). Preoperative NT-proBNP was higher in patients with concomitant procedure than isolated CABG (2146 ± 1858 v 887 ± 1635 ng/L; p = 0.0005). In patients with concomitant procedure ROC analysis showed an AUC of 0.93 for severe circulatory failure with a best cut-off for preoperative NT-proBNP of 3145 ng/L.
Conclusions: Preoperative NT-proBNP predicted in-hospital mortality, severe circulatory failure postoperatively and long-term survival in patients undergoing surgery for acute coronary syndrome but a higher threshold was found in patients having concomitant procedures.
Objectives: Statins decrease cardiovascular events mainly by lowering cholesterol but anti-inflammatory effects also play a role. The effects of the cholesterol absorption inhibitor ezetimibe on markers of inflammation remain unclear. We performed an exploratory post-hoc analysis whether these drugs influence the pro-inflammatory markers interleukin-6 and high-sensitivity C-reactive protein in subjects with very-low cardiovascular risk.
Design: Single center, randomized, parallel 3-group study in 72 healthy men without apparent cardiovascular disease (age 32 ± 9 years, BMI 25.7 ± 3.2 kg/m(2)). Each group of 24 subjects received a 14-day treatment with either simvastatin 40 mg, ezetimibe 10 mg, or their combination.
Results: Baseline IL-6 and hsCRP concentrations in the total cohort were 0.72 ± 0.57 ng/l and 0.40 ± 0.65 mg/l, respectively, with no differences between the 3 groups. Median changes (interquartile range) in IL-6 and hsCRP concentrations were -22% (-43 to 0%) and -30% (-44 to +19%) after simvastatin, -5% (-36 to +30%) and +9% (-22 to +107%) after ezetimibe, and +15% (-15 to +86%) and +1 (-30 to +49%) after the combination. Using a generalized linear model, the multivariable adjusted overall P-values for these changes were 0.008 (IL-6) and 0.1 (hsCRP).
Conclusions: Simvastatin decreases the pro-inflammatory markers IL-6 and almost significantly hsCRP while ezetimibe monotherapy or the combination with simvastatin has no effect.
Objectives: Recent-onset (duration ≤ 1 week) atrial fibrillation (AF) has a high rate of spontaneous conversion to sinus rhythm (SR); still anti-arrhythmic drugs (AAD) are given for conversion purposes. We assessed the effect of AADs by reviewing the literature regarding conversion rates of available drugs in a systematic manner.
Design: PubMed searches were performed using the terms "drug name", "atrial fibrillation", and "clinical study/RCT", and a list of 1302 titles was generated. These titles, including abstracts or complete papers when needed, were reviewed for recent-onset of AF, the use of a control group, and the endpoint of SR within 24 hours. Postoperative and intensive care settings were excluded.
Results: Five AADs were demonstrated to have an effect, and these were Amiodarone, Ibutilide (only one study and risk of torsade de pointes), Flecainide and Propafenone (only to be used in patients without structural heart disease) and Vernakalant. The time taken for conversion differed markedly; Vernakalant converted after 10 minutes, while Amiodarone converted only after 24 hours; Propafenone and Flecainide had conversion times in-between.
Conclusions: For a rapid response in a broad group of patients, Vernakalant appears to be a reasonable first choice, while Flecainide and Propafenone can be used in patients without structural heart disease.
Introduction: Transcatheter aortic valve implantation (TAVI) is established as an attractive treatment option for high-risk patients with aortic valve stenosis. One concern is the high risk of prosthetic valve regurgitation. This study aimed to examine for potential preoperative risk factors for postprocedural transcatheter heart valve regurgitation and to quantify the risk, degree, and consequences of postprocedural regurgitation.
Materials and methods: 100 consecutive patients who underwent femoral (n = 22) or transapical (n = 78) TAVI were retrospectively reviewed. Echocardiographic valve regurgitation and clinical parameters were analyzed over the first year after TAVI.
Results: Seventy-five percent of all patients had prosthetic valve regurgitation. It was, however, only mild or absent in 64% of patients and did not require re-intervention in any of the patients in the series. The severity of the regurgitation appeared unchanged over the one-year follow-up period. Moderate to severe regurgitation was associated with significant yet stable dilatation of the left ventricle over one year and lesser NYHA class improvement three months after TAVI. Asymmetrical native valve calcification increased the risk of paravalvular regurgitation non-significantly.
Conclusion: Transcatheter heart valve regurgitation seems to be mild in the majority of cases and unchanged over a 12 months follow-up period. While affecting left ventricular dimensions in moderate or severe cases, we observed no obvious undesirable consequences of the prosthetic valve regurgitation within the first year.
Objectives: Resuscitation after cardiac arrest may lead to ischemia-reperfusion injury and infarction. We evaluated whether sildenafil, a phosphodiesterase-5 inhibitor, has an impact on recovery after cardiac arrest in a rat cardiac transplantation model.
Design: Sixty-one Fischer344 rats underwent syngeneic heterotopic cardiac transplantation after ischemia and ligation of the left anterior coronary artery of the heart to yield myocardial infarction (IRI + MI). Of these, 22 rats received subcutaneously injected sildenafil (1 mg/kg/day) (IRI +MI + S). Twenty-three additional grafted animals with transplantation only served as controls with ischemia reperfusion injury (IRI). After 2 days, immunohistochemistry for eNOS, and RT-PCR for iNOS and Aquaporin-7 were performed after graft harvesting and histology.
Results: Two days after transplantation, remote intramyocardial arteries were more preserved in IRI + MI + S as compared with IRI +MI and IRI (0.74 ± 0.14, 0.56 ± 0.23 and 0.55 ± 0.22, PSU, p < 0.05, respectively). Decreased eNOS staining confirmed the presence of developing infarction in IRI + MI and IRI + MI + S. The expression of iNOS was significantly lower during IRI + MI +S as compared with IRI + MI (0.02 ± 0.01 and 1.02 ± 0.02, FC, p < 0.05).
Conclusions: Administered at the onset of reperfusion and developing infarction, sildenafil has an impact on myocardial recovery after cardiac arrest and ischemia.
Objectives: To evaluate 15-year survival after coronary artery bypass grafting (CABG) in relation to grade left main stenosis (LMS) and right coronary artery (RCA) obstruction.
Design: Coronary angiographic findings were prospectively collected in 977 patients who had CABG for stable angina during 1994-1995 and were included in the Swedish Coronary Revascularization - Swedish Council of Technology Assessment study.
Results: Significant LMS was present in one fifth of the patients and significant RCA obstruction was found in 61% of those with LMS and in 68% of patients without LMS. The patients were categorized as no LMS (Group I), LMS without RCA obstruction (Group II) or significant LMS with significant right coronary artery (RCA) obstruction (Group III). Early mortality did not differ in the three groups and was 1.2, 1.2% and 0.8% in group I, II and III, respectively. Corresponding survival at 15 years was similar 51%, 47% and 47%, respectively. In multivariable analysis older age, smoking, severe angina, positive stress test, hypertension, diabetes mellitus and ejection fraction < 50% were risk factors for death at 15 years.
Conclusions: Death 15 years after CABG correlated to clinical variables but was not predicted from presence of LMS with or without significant associated RCA obstruction.
Objectives: The impact of myocardial bridge (MB) on left ventricular (LV) systolic synchrony is insufficiently understood.
Design: Thirty-five subjects with isolated mid-left, anterior, descending artery (LAD) MB, preserved LV ejection fraction (LVEF > 50%), and otherwise, normal coronary angiogram were identified from 3607 patients who underwent diagnostic coronary angiography and were evaluated by tissue Doppler imaging and real-time three-dimensional echocardiography (RT3DE). Control subjects consisted of 26 age and sex-matched coronary angiographically "normal" subjects.
Results: MB patients were characterized by reduced, early, diastolic strain rate in LAD-supplied apical segments (lateral and anterior), with prevalence of LV systolic dyssynchrony of 25.7% (9/35). MB patients were further classified by the medians of MB stenosis and length. For MB stenosis < 52.5%, Class I: length < 17 mm (n = 7), Class II: length ≥ 17 mm (n = 10); for stenosis ≥ 52.5%, Class III: length < 17 mm (n = 10), Class IV: length ≥ 17 mm (n = 8). Binary Logistic regression model revealed that higher MB lesion classification (odds ratio: 4.944, 95%CI 1.174-20.82, P < 0.05) and hypertension (odds ratio: 15.32, 95%CI: 1.252-187.6, P < 0.05) are statistically associated with LV systolic dyssynchrony, which was independent of LV mass.
Conclusions: MB in the mid LAD is associated with myocardial dyssynchrony. Hypertensive individuals and those with more severe bridging (determined by length and stenosis) tend to have an increased incidence of dyssynchrony.