Atherectomy-assisted versus percutaneous angioplasty interventions for treatment of symptomatic infra-inguinal peripheral arterial disease.

INTRODUCTION: The role of atherectomy (ATHERO) for the treatment of symptomatic infra-inguinal arterial lesions remains controversial. We evaluated the effectiveness and safety of atherectomy-assisted endovascular interventions in comparison with percutaneous angioplasty (PTA). MATERIAL AND METHODS: A systematic search utilizing MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials was conducted for studies comparing ATHERO with PTA from February 1995 to May 2018. Only studies comparing ATHERO to PTA for symptomatic infra-inguinal disease were included. Random-effects meta-analysis was used to pool the data and endpoints across studies. Study endpoints included vessel dissection, distal embolization, residual stenosis (> 30%), vessel patency at 6 months, target lesion revascularization (TLR) at 12 months and major amputation rates at 1, 6, and 12 months. RESULTS: A total of 2923 patients were included from 8 studies. PTA was associated with higher vessel dissection (OR = 4.00, 95% CI: 1.15-13.86) and lower 12-month major amputation rates (OR = 0.73, 95% CI: 0.59-0.90). There was no significant difference between ATHERO and PTA groups in terms of distal embolization (OR = 0.45, 95% CI: 0.04-4.63), residual stenosis (OR = 1.28, 95% CI: 0.58-2.80), vessel patency at 6 months (OR = 1.27, 95% CI: 0.50-3.22), TLR at 12 months (OR = 1.07, 95% CI: 0.46-2.51), or limb amputation at 1 month (OR = 0.69, 95% CI: 0.44-1.07) or 6 months (OR = 1.54, 95% CI: 0.38-6.15). CONCLUSIONS: In patients undergoing infra-inguinal endovascular interventions, PTA was associated with higher peri-procedural vessel dissection and lower 12-month major amputation rates. Both modalities were associated with similar distal embolization, residual stenosis, and 6-month vessel patency and amputation rates.

Bivalirudin versus unfractionated heparin in peripheral vascular interventions.

BACKGROUND: A number of studies suggest that bivalirudin (BIV) is associated with similar efficacy but reduced bleeding when compared with unfractionated heparin (UFH) in patients undergoing peripheral vascular interventions (PVI). METHODS: A comprehensive literature search was conducted with the electronic databases MEDLINE, EMBASE and CENTRAL. These were queried to identify studies comparing BIV with UFH in PVI. Study endpoints included total bleeding events, major and minor bleeding events and procedural success. Random-effects meta-analysis method was used to pool endpoint odds ratios (OR) for both UFH and BIV with 95% confidence intervals (CI). RESULTS: A total of 12,335 patients (70.6 years; 59.7% male) were included from seven observational cohort studies (two prospective and five retrospective) comparing outcomes between BIV and UFH during PVI between January 2000 and May 2017. Compared with BIV, UFH was associated with significantly higher total bleeding, (OR 1.52 with 95% CI 1.11 to 2.09, p = 0.009), major bleeding (OR 1.38 with 95% CI 1.13 to 1.68, p = 0.002), and minor bleeding (OR 1.51 with 95% CI 1.09 to 2.08, p = 0.01). Procedural success rates were not different between the two groups (BIV vs HEP: OR 0.90 with 95% CI 0.49 to 1.64, p = 0.72) CONCLUSION: Compared with BIV, UFH was associated with more bleeding when used during PVI. There was no significant difference in procedural success between the two anticoagulation strategies.

Thoracic endovascular repair versus medical management for acute uncomplicated type B aortic dissection.

BACKGROUND: Current treatment options and outcomes for acute uncomplicated thoracic Type-B aortic dissection (TBAD) remain unclear between medical management (MED) and thoracic endovascular aortic repair (TEVAR). In this study we aim to compare both strategies in terms of all-cause mortality, aortic dilation, and aortic rupture. METHODS: MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were queried from January 1990 through March 2017. Only studies comparing TEVAR to MED for acute uncomplicated TBAD were included. Random-effects meta-analysis was used to pool outcomes across studies. Study outcomes included short (1 month), intermediate (1 year), and mid-term (2-5 year) all-cause mortality. Additional outcomes included aortic dilation and rupture at 1 year. RESULTS: A total of 1,960 patients (64.3 years; 75.8% male) were included from six studies (one prospective and five retrospective). No difference was observed in short-term (odd ratio [OR] 0.73 with 95% confidence interval [CI] 0.47 to 1.12, P = 0.15), intermediate (OR 0.99 with 95% CI 0.56 to 1.73, P = 0.96), or mid-term all-cause mortality (OR 1.12 with 95% CI 0.54 to 2.32, P = 0.75). No difference in aortic dilation with either modality was noted at 1-year (OR 1.11 with 95% CI 0.76 to 1.64, P = 0.59). TEVAR was associated with a significantly lower 1-year risk of aortic rupture (OR 2.49 with 95% CI 1.23 to 5.06, P = 0.01). CONCLUSION: There were no short, intermediate, or mid-term differences in mortality between TEVAR or MED in patients with acute uncomplicated TBAD. Although the dilation rate was similar between both groups, TEVAR was associated with lower likelihood of aortic rupture at 1 year.

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

OBJECTIVES: To compare outcomes of fractional flow reserve (FFR) to angiography (ANGIO) guided percutaneous coronary intervention (PCI). BACKGROUND: The results of a recent randomized controlled trial reported unfavorable effects of routine measurement of FFR, thereby questioning its validity in improving clinical outcomes. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Comparison of Outcomes of ST-Elevation Myocardial Infarction Treated by Percutaneous Coronary Intervention During Off-Hours Versus On-Hours.

Previous studies have reported worse outcomes and longer door-to-balloon times (DBTs) in patients presenting with ST-elevation myocardial infarction (STEMI) after normal working hours, during weekends, and on holidays (off-hours) compared with normal business hours (on-hours). Recent studies, however, have reported similar outcomes regardless of presentation time. MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were queried from January 1990 through December 2016. Only studies comparing STEMI outcomes during off-hours versus on-hours with percutaneous coronary intervention were included. A random-effects meta-analysis model was used to pool outcomes across the studies. Clinical end points included short- (<30 days of presentation), intermediate- (at 1 to 2 years), and long-term (at 3 to 4 years) stent thrombosis, mortality, recurrent myocardial infarction (MI), and major adverse cardiovascular events (MACEs). A total of 86,776 patients (62 years and 74.5% male) were identified from 39 studies. There was no significant difference between both groups with regard to mean DBT (odds ratio [OR] 0.74, 95% confidence interval [CI] -2.73 to 4.22, p = 0.67) or median DBT (p = 0.19). There was no significant difference between the 2 groups for short-term end points including mortality (OR 1.11, 95% CI 0.99 to 1.25, p = 0.08), MI (OR 1.25, 95% CI 0.90 to 1.74, p = 0.18), MACE (OR 1.06, 95% CI 0.93 to 1.20, p = 0.40), or stent thrombosis (OR 1.23, 95% CI 0.83 to 1.82, p = 0.31). Similarly, intermediate-term end points were not statistically different for mortality (OR 0.97, 95% CI 0.89 to 1.05, p = 0.46), MI (OR 0.86, 95% CI 0.73 to 1.02, p = 0.08), or MACE (OR 1.00, 95% CI 0.92 to 1.08, p = 0.98). Long-term end points did not differ statistically between groups for mortality (OR 0.95, 95% CI 0.83 to 1.09, p = 0.46), MI (OR 1.19, 95% CI 0.77 to 1.84, p = 0.44), or MACE (OR 0.98, 95% CI 0.89 to 1.08, p = 0.67). In conclusion, patients presenting with STEMI during off-hours and treated with percutaneous coronary intervention had similar short-, intermediate-, and long-term outcomes compared with patients presenting during on-hours. DBT was not affected by the time of presentation.

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

BACKGROUND: A 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. METHODS: A 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. RESULTS: A 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). CONCLUSIONS: In patients presenting with ALI (<2 weeks of duration), ENDO and SURG approaches have similar rates of short-term and 12 month mortality, limb amputation and recurrent ischemia.

Hemorrhagic and ischemic outcomes of Heparin vs. Bivalirudin in carotid artery stenting: A meta-analysis of studies.

INTRODUCTION: Bivalirudin, has been shown to have comparable efficacy and better safety profile when compared to unfractionated heparin (UFH) in percutaneous coronary interventions. Bivalirudin's safety in carotid artery stenting (CAS) was associated with better outcomes than heparin in some studies. In this Meta analysis we examine the hemorrhagic and ischemic outcomes associated with Bivalirudin compared to UFH during CAS. METHODS: A comprehensive literature search was conducted with the electronic databases MEDLINE, EMBASE, and CENTRAL. Random-effects meta-analysis method was used to pool risk ratio (RR) for both Heparin and Bivalirudin with 95% confidence interval (CI). Study outcomes included hemorrhagic complications; major/minor bleeding and intracranial hemorrhage (ICH) as well as ischemic complications including ischemic stroke, myocardial infarction, and 30 day mortality. RESULTS: A total of four studies were included enrolling 7,784 patients. Compared to UFH, Bivalirudin was associated with significantly lower major bleeding events with a relative risk (RR) of 0.53 (95% CI: 0.35-0.80; I2 = 0%). Minor bleeding events were significantly lower in the Bivalirudin group with a RR of 0.41 (95% CI: 0.2-0.82; I2 = 0%). Looking into other outcomes, there were no significant differences between anticoagulation strategies in terms of ischemic stroke (RR 0.8, with 95% CI: 0.60-1.06), intracranial hemorrhage (RR 0.73 with 95% CI: 0.27-1.98), myocardial infarction (RR 1.01 with 95% CI: 0.59-1.73) or 30 day mortality (RR 0.83 with 95% CI: 0.47-1.47). CONCLUSION: Compared to UFH, Bivalirudin is associated with lower bleeding risk when used during CAS. © 2016 Wiley Periodicals, Inc.

Proximal balloon occlusion versus distal filter protection in carotid artery stenting: A meta-analysis and review of the literature.

INTRODUCTION: Carotid artery stenting (CAS) is typically performed using embolic protection devices (EPDs) as a means to reduce the risk of procedure-related stroke. In this study, we compared procedural morbidity and mortality associated with distal (D-EPD) vs. proximal (P-EPD) protection. METHODS: MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were queried from January 1998 through May 2015. Only studies comparing (D-EPD) and (P-EPD) were included. Two independent reviewers selected and appraised studies and extracted data in duplicate. Random-effects meta-analysis was used to pool outcomes across studies. Heterogeneity of treatment effect among studies was assessed using the I2 statistics. Publication bias was assessed using inspection of funnel plots. The primary endpoints included 30-day mortality and stroke. Secondary endpoints included new cerebral lesions on diffusion-weighted magnetic resonance imaging (DW-MRI) and contralateral lesions on DW-MRI. RESULTS: A total of 12,281 patients were included from 18 studies (13 prospective and 5 retrospective) comparing (D-EPD) and (P-EPD) in the setting of CAS. The mean patient age was 69 years and 64% of patients were male. No evidence of publication bias was detected. There was no significant difference between the two modalities in terms of the risk of stroke (risk difference [RD] 0.0, 95% confidence interval [CI] -0.01 to 0.01) or mortality (RD 0.0, 95% CI -0.01 to 0.01) nor was there any difference in the incidence of new cerebral lesions on DW-MRI or contralateral DW-MRI lesions. CONCLUSIONS: In patients undergoing CAS, both D-EPD and P-EPD provide similar levels of protection from peri-procedural stroke and 30 days mortality. © 2016 Wiley Periodicals, Inc.

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.).

An open sarcolemmal adenosine triphosphate-sensitive potassium channel is necessary for detrimental myocyte swelling secondary to stress.

BACKGROUND: Stress (exposure to hyperkalemic cardioplegia, metabolic inhibition, or osmotic) results in significant myocyte swelling and reduced contractility. In contrast to wild-type mice, these detrimental consequences are not observed in mice lacking the Kir6.2 subunit of the sarcolemmal ATP-sensitive potassium (sK(ATP)) channel after exposure to hyperkalemic cardioplegia. The hypothesis for this study was that an open sK(ATP) channel (Kir6.2 and SUR2A subunits) is necessary for detrimental myocyte swelling to occur in response to stress. METHODS AND RESULTS: To investigate the role of the sK(ATP) channel in stress-induced myocyte swelling, high-dose pharmacological sK(ATP) channel blockade and genetic deletion (knockout of Kir6.2 subunit) were used. Myocytes were exposed sequentially to Tyrode control (20 minutes), test (stress) solution (20 minutes), and Tyrode control (20 minutes). To evaluate pharmacological channel blockade, myocytes were exposed to hyperkalemic cardioplegia (stress) with and without a K(ATP) channel blocker. To evaluate the effects of genetic deletion, wild-type and sK(ATP) knockout [Kir6.2(-/-)] myocytes were exposed to metabolic inhibition (stress). Myocyte volume was recorded using image-grabbing software. Detrimental myocyte swelling was prevented by high-dose sK(ATP) channel blockade (glibenclamide or HMR 1098) but not mitochondrial K(ATP) channel blockade (5-hydroxydecanoate) during exposure to hyperkalemic cardioplegia. Genetic deletion of the sK(ATP) channel prevented significant myocyte swelling in response to metabolic inhibition. CONCLUSIONS: K(ATP) channel openers prevent detrimental myocyte swelling and reduce contractility in response to stress through an unknown mechanism. Paradoxically, the present data support a role for sK(ATP) channel activation in myocyte volume derangement in response to stress.

Diazoxide maintenance of myocyte volume and contractility during stress: evidence for a non-sarcolemmal K(ATP) channel location.

OBJECTIVE: Animal and human myocytes demonstrate significant swelling and reduced contractility during exposure to stress (metabolic inhibition, hyposmotic stress, or hyperkalemic cardioplegia), and these detrimental consequences may be inhibited by the addition of diazoxide (adenosine triphosphate-sensitive potassium channel opener) via an unknown mechanism. Both SUR1 and SUR2A subunits have been localized to the heart, and mouse sarcolemmal adenosine triphosphate-sensitive potassium channels are composed of SUR2A/Kir6.2 subunits in the ventricle and SUR1/Kir6.2 subunits in the atria. This study was performed to localize the mechanism of diazoxide by direct probing of sarcolemmal adenosine triphosphate-sensitive potassium channel current and by genetic deletion of channel subunits. METHODS: Sarcolemmal adenosine triphosphate-sensitive potassium channel current was recorded in isolated wild-type ventricular mouse myocytes during exposure to Tyrode's solution, Tyrode's + 100 µmol/L diazoxide, hyperkalemic cardioplegia, cardioplegia + diazoxide, cardioplegia + 100 µmol/L pinacidil, or metabolic inhibition using whole-cell voltage clamp (N = 7-12 cells per group). Ventricular myocyte volume was measured from SUR1(-/-) and wild-type mice during exposure to control solution, hyperkalemic cardioplegia, or cardioplegia + 100 µmol/L diazoxide (N = 7-10 cells per group). RESULTS: Diazoxide did not increase sarcolemmal adenosine triphosphate-sensitive potassium current in wild-type myocytes, although they demonstrated significant swelling during exposure to cardioplegia that was prevented by diazoxide. SUR1(-/-) myocytes also demonstrated significant swelling during exposure to cardioplegia, but this was not altered by diazoxide. CONCLUSIONS: Diazoxide does not open the ventricular sarcolemmal adenosine triphosphate-sensitive potassium channel but provides volume homeostasis via an SUR1-dependent pathway in mouse ventricular myocytes, supporting a mechanism of action distinct from sarcolemmal adenosine triphosphate-sensitive potassium channel activation.

Recurrent mitral regurgitation and risk factors for early and late mortality after mitral valve repair for functional ischemic mitral regurgitation.

BACKGROUND: Mortality for patients with coronary artery disease and functional ischemic mitral regurgitation (IMR) remains high regardless of the treatment strategy. Data regarding risk factors, progression of MR, and cause of death in this subgroup are limited. METHODS: A retrospective study was performed on 257 consecutive patients undergoing mitral valve repair exclusively for IMR from 1996 to 2005. Potential preoperative and perioperative risk factors for death and postoperative echocardiographic data were recorded. RESULTS: Preoperative echocardiography demonstrated 3+ to 4+ MR in 98.4% (252 of 257). Concomitant coronary artery bypass grafting was performed in 80.9% (208 of 257). Operative mortality was 10.1% (26 of 257). Overall survival by Kaplan-Meier analysis was 68.3% at 3 years and 52.0% at 5 years. Factors associated with late mortality by multivariate analysis include advanced age (relative risk [RR], 1.037; 95% confidence interval [CI], 1.016 to 1.059; p < or = 0.001), preoperative dialysis (RR, 3.504; 95% CI, 1.590 to 7.720; p = 0.008), and diabetes (RR, 2.047; 95% CI, 1.319 to 3.177; p = 0.001). Echocardiographic data at 20 +/- 25 months were available in 57% (147 of 257). Their survival by Kaplan-Meier analysis was 76.4% at 3 years and 65.1% at 5 years with 0 to 2+ MR postoperatively (n = 106) vs 61.3% and 35.8% with 3+ to 4+ MR (n = 41; p = 0.003). Cause of death was available in 72.3% (60 of 83) of late deaths, with 42.2% (35 of 83) attributed to cardiac causes and 30.1% (25 of 83) noncardiac. CONCLUSIONS: Mortality for IMR remains high despite surgical management and may be related to risk factors for progression of coronary artery disease. Despite repair, MR progresses in many patients and is associated with poor survival, although more detailed prospective data are needed to characterize this relationship.

Maintenance of myocyte volume homeostasis during stress by diazoxide is cardioprotective.

BACKGROUND: We previously demonstrated that myocyte swelling and reduced contractility secondary to hyperkalemic cardioplegia and hyposmotic stress are attenuated by the addition of diazoxide, an adenosine triphosphate-sensitive potassium channel (K(ATP)) opener. The goal of this study was to investigate the effect of diazoxide on myocyte swelling and reduced contractility after metabolic inhibition and to attempt to summarize the potential mechanisms involved. METHODS: Isolated rabbit myocytes were perfused with Tyrode's control solution for 20 minutes, followed by test solution for 20 minutes. Test solutions included (1) Tyrode's control, (2) a metabolic inhibition solution containing sodium cyanide and 2-deoxyglucose, (3) metabolic inhibition plus diazoxide, (4) metabolic inhibition plus diazoxide plus HMR1098 (a sarcolemmal K(ATP)-channel blocker), or (5) metabolic inhibition plus diazoxide plus 5-hydroxydeconoate (a mitochondrial K(ATP)-channel blocker). Myocytes were then reexposed to Tyrode's solution for 20 minutes. Volume measurements were taken every 5 minutes. Contractility was recorded using edge-detection software at baseline and at 10 and 20 minutes of reexposure to Tyrode's solution. RESULTS: Simulated ischemia (metabolic inhibition) caused significant myocyte swelling and associated reduced contractility. The addition of diazoxide abolished myocyte swelling and attenuated the associated reduced contractility. Observations with diazoxide were unchanged by the addition of HMR 1098 or 5-hydroxydeconoate. CONCLUSIONS: Diazoxide, with or without either K(ATP)-channel blocker, attenuated the significant myocyte swelling and reduced contractility secondary to metabolic inhibition. These data suggest a role for diazoxide, independent of the K(ATP) channel, in myocyte volume homeostasis. In addition, the prevention of myocyte swelling resulted in improved contractility, consistent with previous data and the hypothesis that myocyte swelling may participate in the phenomenon of myocardial stunning.

Significance of neurologic complications in the modern era of cardiac transplantation.

BACKGROUND: Severe neurologic complications after cardiac transplantation are devastating outcomes of this life-saving procedure. Incidence, risk factors, and morbidity of neurologic events in the modern era of cardiac transplantation are yet to be defined. METHODS: Between 1996 and 2005, 200 patients (64% men; mean age, 49 +/- 12 years) underwent heart transplantation at our institution. Overall, 46 patients (23%) showed a wide spectra of early neurologic complications. RESULTS: Cause of ischemic complications was stroke in 11 patients (7 had concomitant epileptic seizures) and transient ischemic attack (TIA) in 7. Encephalopathy (n = 10), epileptic seizures unrelated to focal cerebral lesions (n = 7), severe headache (n = 6), cerebral infection (n = 3), and peripheral nervous system injuries (n = 2) completed the spectra of adverse neurologic outcomes. Multivariate analysis identified advanced age (p = 0.03), preoperative left ventricular assist device support (p = 0.02), preoperative intraaortic balloon pump support (p < 0.001), prolonged cardiopulmonary bypass time (p < 0.001), and postoperative hepatic failure (p = 0.04) as independent predictors of early neurologic complications. Postoperative morbidities associated with neurologic complications included longer ventilation time (p < 0.001), longer stay in the intensive care unit (p < 0.001), and higher incidence of pneumonia (p < 0.001) and sepsis (p = 0.01) compared with patients without neurologic events. There was a trend toward higher in-hospital mortality (15% versus 6%, p = 0.07), but there was no difference in long-term survival (65% versus 78%, p = 0.15). CONCLUSIONS: Despite rigorous pretransplantation screening, neurologic complications were common after cardiac transplantation. Most frequently, these complications were not the actual cause of death, but they significantly contributed to increased morbidity. Preoperative mechanical circulatory support requirement was the strongest predictor for adverse neurologic outcome.

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

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) < or = 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 < 0.05). 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.

Role of the sarcolemmal adenosine triphosphate-sensitive potassium channel in hyperkalemic cardioplegia-induced myocyte swelling and reduced contractility.

BACKGROUND: Hyperkalemic cardioplegia (Plegisol) has been shown to result in myocyte swelling and reduced contractility. We have demonstrated the elimination of these detrimental effects by the addition of an adenosine triphosphate-sensitive K+ (KATP) channel opener. To examine whether the mitochondrial or sarcolemmal KATP channel might be involved, volume and contractility in isolated myocytes from wild-type mice and mice lacking the sarcolemmal KATP channel (Kir6.2-/-) were evaluated. METHODS: Myocytes were perfused for 20 minutes each with control 37 degrees C Tyrode's solution, test solution, and then control solution. Test solutions were (n = 10 per group) either 9 degrees C Plegisol or 9 degrees C Plegisol with 100 micromol/L of diazoxide, a putative mitochondrial-specific KATP channel opener. Cell volume and contractility were measured by digital video microscopy at baseline and during the test solution and reexposure periods. RESULTS: Myocytes from wild-type mice, perfused with 9 degrees C Plegisol, demonstrated significant cell swelling (11.2% +/- 0.4%; p < 0.01) and diminished contractility (32.5% +/- 9.6% reduction in percent shortening, 47.2% +/- 10.1% reduction in peak velocity of shortening, and 52.0% +/- 8.8% reduction in peak velocity of relengthening; p < 0.05) versus baseline. Cell swelling and diminished contractility were significantly reduced by the addition of diazoxide. In Kir6.2-/- myocytes, Plegisol caused a greatly reduced level of cell swelling (3.2% +/- 0.1%; p < 0.01), and this was unaffected by diazoxide. Contractility was unchanged in Kir6.2-/- myocytes after Plegisol. CONCLUSIONS: The sarcolemmal KATP channel appears necessary for exaggerated cell swelling and reduced contractility to occur after hyperkalemic cardioplegia in mouse myocytes.

Hyperkalemic cardioplegia-induced myocyte swelling and contractile dysfunction: prevention by diazoxide.

BACKGROUND: Hyperkalemic cardioplegia (9 degrees C) results in significant myocyte swelling and reduced contractility, representing a possible mechanism of myocardial stunning. Adenosine triphosphate-sensitive potassium channel (KATP) openers have been shown to ameliorate stunning. This study evaluated the hypothesis that a KATP opener would prevent hyperkalemic cardioplegia-induced myocyte swelling and reduced contractility. METHODS: Isolated rabbit myocytes were perfused with 37 degrees C Tyrode's solution for 20 minutes, followed by test solution (9 degrees C or 37 degrees C) including control Tyrode's, Tyrode's + 100 micromol/L diazoxide (KATP opener), St. Thomas's solution; or 9 degrees C St. Thomas's + 100 micromol/L diazoxide or St. Thomas's + 100 micromol/L diazoxide + 20 micromol/L HMR1098 or 50 micromol/L 5-hydroxydeconoate (KATP blockers) for 20 minutes (n = 8 per group). Myocytes were then reexposed to 37 degrees C Tyrode's solution for 20 minutes. Volume and contractility were measured by videomicroscopy and video-based edge detection, respectively. RESULTS: St. Thomas's solution (9 degrees C) caused significant myocyte swelling and associated reduced contractility (p < 0.05). The addition of diazoxide abolished myocyte swelling (p < 0.0001), and eliminated the associated reduced contractility (p < 0.05). Findings were unchanged by the addition of HMR 1098 and 5-hydroxydeconoate. CONCLUSIONS: Diazoxide prevented myocyte swelling and reduced contractility secondary to hyperkalemic cardioplegia, and this was unchanged by the addition of either KATP channel blocker. Prevention of myocyte swelling was associated with improved contractility, consistent with the hypothesis that myocyte swelling may be a mechanism of myocardial stunning. Diazoxide may play a role in myocyte volume homeostasis by means of a mechanism separate from opening the KATP channel.