Diazoxide maintains human myocyte volume homeostasis during stress

BACKGROUND: Exposure to hypothermic hyperkalemic cardioplegia, hyposmotic stress, or metabolic inhibition results in significant animal myocyte swelling (6% to10%) and subsequent reduced contractility (10% to 20%). Both are eliminated by the adenosine triphosphate-sensitive potassium channel opener diazoxide (DZX). The relationship between swelling and reduced contractility suggests that the structural change may represent one mechanism of postoperative myocardial stunning. This study evaluated human myocyte volume during stress to investigate if similar phenomena exist in human myocytes. METHODS AND RESULTS: Human atrial myocytes isolated from tissue obtained during cardiac surgery were perfused with Tyrode's physiological solution (20 minutes, 37°C), test solution (20 minutes), and Tyrode's (37°C, 20 minutes). Test solutions (n=6 to 12 myocytes each) included Tyrode's (37°C or 9°C), Tyrode's+DZX (9°C), hyperkalemic cardioplegia (9°C)±DZX, cardioplegia+DZX+HMR 1098 (sarcolemmal adenosine triphosphate-sensitive potassium channel inhibitor, 9°C), cardioplegia+DZX+5-hydroxydeconoate (mitochondrial adenosine triphosphate-sensitive potassium channel inhibitor, 9°C), mild hyposmotic solution±DZX, metabolic inhibition±DZX, and metabolic inhibition+DZX+5-hydroxydeconoate. Myocyte volume was recorded every 5 minutes. Exposure to hypothermic hyperkalemic cardioplegia, hyposmotic stress, or metabolic inhibition resulted in significant human myocyte swelling (8%, 7%, and 6%, respectively; all P<0.05 vs control). In all groups, the swelling was eliminated or lessened by DZX. The addition of channel inhibitors did not significantly alter results. CONCLUSIONS: DZX maintains human myocyte volume homeostasis during stress via an unknown mechanism. DZX may prove to be clinically useful following the elucidation of its specific mechanism of action. (J Am Heart Assoc. 2012;1:jah3-e000778 doi: 10.1161/JAHA.112.000778.

Endovascular versus surgical treatment for acute limb ischemia: a systematic review and meta-analysis of clinical trials

BackgroundA number of small studies have suggested that outcomes following endovascular (ENDO) therapy are comparable to those following surgical (SURG) revascularization for patients presenting with acute limb ischemia (ALI). We sought to compare mortality, limb amputation and recurrent ischemia across both revascularization strategies.MethodsA comprehensive database search of MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials (CENTRAL) electronic databases from January 1990 through January 2016 was performed to identify studies of ENDO versus SURG for ALI. Two independent reviewers selected studies and extracted the data. Random-effects meta-analysis was used to pool results across studies. Heterogeneity of treatment effect among trials was assessed using the I2 statistics. The primary endpoints were mortality and limb amputation at 1 month, 6 and 12 months. Secondary endpoint was recurrent ischemia at one year.ResultsA total of 1,773 patients were included from six studies (five randomized prospective and one observational retrospective) comparing ENDO and SURG in the setting of ALI. The mean age was 67 years and 65% of patients were male. There were no differences in mortality between the two groups at 1 month [risk ratio (RR) for ENDO vs. SURG is 0.70; 95% confidence interval (CI), 0.33 to 1.50], 6 months (RR 1.12; CI, 0.78 to 1.61) or 12 months (RR 0.74; CI, 0.29 to 1.85). Similarly, there was no significant difference in amputation rates between ENDO and SURG at 1 month (RR 0.75; CI, 0.40 to 1.42), 6 months (RR 0.87; CI, 0.52 to 1.48) or 12 months (RR 0.81; CI, 0.55 to 1.18). When looking into secondary outcomes, recurrent ischemia was not different between the two groups (RR 1.12; CI, 0.75 to 1.67).ConclusionsIn patients presenting with ALI (&lt;2 weeks of duration), ENDO and SURG approaches have similar rates of short-term and 12 month mortality, limb amputation and recurrent ischemia

Implantable cardioverter-defibrillators improve survival after coronary artery bypass grafting in patients with severely impaired left ventricular function

Abstract Objective Patients with severe left ventricular (LV) dysfunction have a poor long term survival despite complete surgical revascularization. Recent data suggests that the use of Implantable Cardioverter-Defibrillator (ICD) improves survival in patients with severe LV dysfunction. We compared the survival impact of ICD implantation in patients with severe LV dysfunction who underwent CABG. Methods Between January 1996 and August 2004, 305 patients with LV ejection fraction (EF) ≤25% had CABG surgery at our institution. Demographics of patients who had received an ICD (ICD+) in the post -operative period was compared to those without ICD (ICD-). Survival was evaluated by the Kaplan-Meier method. Results Of the entire group, 35 (11.5%) patients received an ICD with a median of 2 (+/-2) years after CABG. Indication for ICD implantation was clinical evidence of non sustained ventricular tachycardia (NSVT). There were no differences between the 2 groups with respect to age, gender, NYHA classification, number of bypasses, or other co-morbidities. Survival at 1, 3 and 5 years was 88%, 79%, and 67% for the ICD- group compared to 94%, 89% and 83% for the ICD+ group, respectively (figure, p Conclusion Implantation of ICD after CABG confers improved short and long term survival benefit to patients with severe LV dysfunction. Prophylactic ICD implantation in the setting of severe LV dysfunction and CABG surgery should be considered.</p

Fractional flow reserve versus angiography guided percutaneous coronary intervention: An updated systematic review

To compare outcomes of fractional flow reserve (FFR) to angiography (ANGIO) guided percutaneous coronary intervention (PCI). The results of a recent randomized controlled trial reported unfavorable effects of routine measurement of FFR, thereby questioning its validity in improving clinical outcomes. MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were queried from January, 2000 through December, 2016 and studies comparing FFR and ANGIO guided PCI were included. Clinical endpoints assessed during hospitalization and at follow-up (>9 months) included: myocardial infarction (MI), major adverse cardiovascular events (MACE), target lesion revascularization (TLR), and all-cause mortality. Additional endpoints included number of PCIs performed, procedure cost, procedure time, contrast volume, and fluoroscopy time. A total of 51,350 patients (age 65 years, 73% male) were included from 11 studies. The use of FFR was associated with significantly lower likelihood of MI during hospitalization (OR 0.54, 95% CI: 0.39 to 0.75, P = 0.0003) and at follow-up (OR 0.53, 95% CI: 0.40 to 0.70, P = 0.00001). Similarly, FFR-PCI was associated with lower in-hospital MACE (OR 0.51, 95% CI: 0.37 to 0.70, P = 0.0001) and follow-up MACE (OR 0.63, 95% CI: 0.47 to 0.86, P = 0.004). In-hospital TLR was lower in the FFR-PCI group (OR 0.62, 95% CI: 0.40 to 0.97, P = 0.04), but not at follow-up (OR 0.83, 95% CI: 0.50 to 1.37, P = 0.46). There was no difference of in-hospital (OR 0.58, 95% CI: 0.31 to 1.09, P = 0.09) or follow-up all-cause mortality (OR 0.84, 95%CI: 0.59 to 1.20, P = 0.34). FFR-PCI was associated with significantly less PCI (OR 0.04, 95% CI: 0.01 to 0.15, P = 0.00001) with lower procedure cost (Mean Difference -4.27, 95% CI: -6.61 to -1.92, P = 0.0004). However, no difference in procedure time (Mean Difference 0.79, 95% CI: -2.41 to 3.99, P = 0.63), contrast use (Mean Difference -8.28, 95% CI: -24.25 to 7.68, P = 0.31) or fluoroscopy time (Mean Difference 0.38, 95% CI: -2.54 to 3.31, P = 0.80) was observed. FFR-PCI as compared to ANGIO-PCI is associated with lower in-hospital and follow-up MI and MACE rates. Although, in-hospital TLR was lower in the FFR-PCI group, this benefit was not present after 9 months. FFR-PCI group was also associated with less PCI and lower procedure costs with no effect on procedure time, contrast volume or fluoroscopy time