Ashraf S. Al-Dadah

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.

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 Tyrodes physiological solution (20 minutes, 37°C), test solution (20 minutes), and Tyrodes (37°C, 20 minutes). Test solutions (n=6 to 12 myocytes each) included Tyrodes (37°C or 9°C), Tyrodes+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 (sKATP) channel after exposure to hyperkalemic cardioplegia. The hypothesis for this study was that an open sKATP 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 sKATP channel in stress-induced myocyte swelling, high-dose pharmacological sKATP 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 KATP channel blocker. To evaluate the effects of genetic deletion, wild-type and sKATP 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 sKATP channel blockade (glibenclamide or HMR 1098) but not mitochondrial KATP channel blockade (5-hydroxydecanoate) during exposure to hyperkalemic cardioplegia. Genetic deletion of the sKATP channel prevented significant myocyte swelling in response to metabolic inhibition. Conclusions— KATP 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 sKATP channel activation in myocyte volume derangement in response to stress.

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

ObjectivePatients 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.MethodsBetween 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.ResultsOf 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).ConclusionImplantation 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.

Diazoxide prevents myocyte swelling and reduced contractility via a sarcolemmal KATP channel-independent mechanism

ETHODS: Tissue samples (1cm, n 6) cut from five regions of he aorta and pulmonary artery–anterior, posterior, and each sinus, ere subjected to displacement-controlled equibiaxial stretch testing. tress-strain data recorded was used to derive strain energy functions or segregated regions of aortic and autograft FEM meshes. Systolic ressure curves were input to LS-DYNA as loading conditions of the EM, and the degree and direction of tissue dilation was examined to valuate post-operative root dynamics.

Epicardial Microwave Ablation on the Beating Heart for Atrial Fibrillation: The Dependency of Lesion Depth on Cardiac Output: 19

BACKGROUND Microwave energy is commonly used on the beating heart to create lesions for the surgical treatment of atrial fibrillation. However, lesion transmurality is likely to depend on several factors including tissue thickness and blood flow. This study was designed to determine the effect of cavitary blood flow on transmurality of acute atrial lesions with the FLEX 10 (Guidant Corporation, Santa Clara, Calif) microwave device. METHODS Six pigs underwent median sternotomy and were placed on cardiopulmonary bypass. Microwave lesions on the atrium were performed for 60 seconds at 65 Watts at 4 different levels of cardiac output by varying cardiopulmonary bypass flow rates. Cardiac output was measured with a pulmonary artery flow probe. Four additional lesions on 2 animals were done for 120 seconds at 65 Watts with 0.0 to 0.5 L/min cardiac output. The animals were sacrificed, and tissue was stained with 2,3,5-triphenyltetrazolium chloride and sectioned at 5-mm intervals. Lesion depth and width were determined from photomicrographs. RESULTS Sixty-second lesions were transmural in 90%, 65%, 54%, and 46% of atrial sections at cardiac output of 0.0 to 0.5 L/min, 0.6 to 1.9 L/min, 2.0 to 3.9 L/min, and 4.0 L/min or greater, respectively (P < .001). When ablations were performed for 120 seconds with a cardiac output of 0.0 to 0.5 L/min, 100% of lesions were transmural. Lesion width was also related to cardiac output, with the widest lesions produced when cardiac output was 0.0 to 0.5 L/min. CONCLUSIONS Acute microwave ablation lesion depth and width are strongly dependent on the magnitude of cardiac output. Transmural lesions can be reliably produced on the porcine heart only while on cardiopulmonary bypass.