John Um

Unique Antibody Responses to Malondialdehyde-Acetaldehyde (MAA)-Protein Adducts Predict Coronary Artery Disease

Malondialdehyde-acetaldehyde adducts (MAA) have been implicated in atherosclerosis. The purpose of this study was to investigate the role of MAA in atherosclerotic disease. Serum samples from controls (n = 82) and patients with; non-obstructive coronary artery disease (CAD), (n = 40), acute myocardial infarction (AMI) (n = 42), or coronary artery bypass graft (CABG) surgery due to obstructive multi-vessel CAD (n = 72), were collected and tested for antibody isotypes to MAA-modifed human serum albumin (MAA-HSA). CAD patients had elevated relative levels of IgG and IgA anti-MAA, compared to control patients (p<0.001). AMI patients had a significantly increased relative levels of circulating IgG anti-MAA-HSA antibodies as compared to stable angina (p<0.03) or CABG patients (p<0.003). CABG patients had significantly increased relative levels of circulating IgA anti-MAA-HSA antibodies as compared to non-obstructive CAD (p<0.001) and AMI patients (p<0.001). Additionally, MAA-modified proteins were detected in the tissue of human AMI lesions. In conclusion, the IgM, IgG and IgA anti-MAA-HSA antibody isotypes are differentially and significantly associated with non-obstructive CAD, AMI, or obstructive multi-vessel CAD and may serve as biomarkers of atherosclerotic disease.

Outcomes in Patients with Severe Preexisting Renal Dysfunction After Continuous-Flow Left Ventricular Assist Device Implantation.

The aim of this study was to evaluate clinical outcomes after left ventricular assist device (LVAD) implantation in patients with severe pre-LVAD renal dysfunction (RD). The cohort of 165 consecutive patients implanted with HeartMate II LVADs was divided into two groups: 1) baseline glomerular filtration rate (bGFR) ⩽ 40 ml/min/1.73 m2 (n = 30), and 2) GFR > 40 ml/min/1.73 m2 (n = 135). In both groups, GFR increased significantly at 1 month and then declined, remaining higher than the pre-LVAD level in the bGFR ⩽ 40 group and returning back to the pre-LVAD level in the bGFR > 40 group by 1 year post-LVAD follow-up. Post-LVAD dialysis was used in 20% of the bGFR ⩽ 40 patients and 7% of the bGFR > 40 patients (p = 0.02). By 3 months, 14% patients had GFR ⩽ 40 ml/min/1.73 m2. Grade ≥2 tricuspid regurgitation (TR) (odds ratio [OR], 3.4; 95% confidence interval [CI], 1.23–10.28; p = 0.02) and model for end-stage liver disease-XI score ≥ 17 (OR, 4.2; 95% CI, 1.45–12.24; p = 0.01) were risk factors for severe RD at 3 months after LVAD implantation. Eight bGFR ⩽ 40 patients underwent heart transplantation. Carefully selected patients with advanced heart dysfunction and bGFR ⩽ 40 ml/min/1.73 m2 can improve kidney function with LVAD support and be able to bridge to isolated heart transplantation. Additional research is needed to refine patient selection for LVAD.

Combined heart and liver transplantation against positive cross-match for patient with hypoplastic left heart syndrome

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Sinus tachycardia is associated with impaired exercise tolerance following heart transplantation

Sinus tachycardia often presents in heart transplantation (HTx) recipients, but data on its effect on exercise performance are limited.

Cardiac Assist Devices and Hemodialysis Catheter Procedures - What Do the Nephrologists Need to Know?

The use of ventricular assist devices (VAD) and total artificial heart (TAH) is increasing rapidly, and a large proportion of these device recipients already have or will develop severe renal dysfunction at the time of device implantation. As a consequence, nephrologists are becoming more and more involved in the care of this challenging population. As nephrologists take upon themselves many aspects of dialysis vascular access care, they need to be familiar with the special circumstances of performing hemodialysis catheter procedures in these patients. This review describes the important characteristics of these devices that have serious implications for the technique of placing or replacing dialysis catheters. These implications apply for both tunneled and nontunneled dialysis catheters and so concern all nephrologists, not only the interventionalists. We describe the important anatomical factors, anticoagulation management, device management, vascular access management and technical considerations of placing or replacing tunneled and nontunneled hemodialysis catheters from the perspective of a nephrologist establishing and maintaining lifesaving dialysis vascular access. Without a good understanding of these devices, serious consequences such as VAD rotor damage or blockage, or artificial heart valve blockage or damage can occur. These artificial devices are lifesaving, and any such complication is unacceptable. This review describes steps to minimize the risks.

Cytomegalovirus reactivation and colitis after left ventricular assist device placement

We describe two patients who developed gastrointestinal bleeding due to cytomegalovirus (CMV) colitis after placement of a HeartMate II left ventricular assist device (LVAD). We aim to raise awareness of CMV colitis as a possible cause of gastrointestinal bleeding after LVAD placement and discuss potential mechanisms for CMV reactivation and areas for future research.

Molecular discoveries and treatment strategies by direct reprogramming in cardiac regeneration

&NA; Cardiac tissue has minimal endogenous regenerative capacity in response to injury. Treatment options are limited following tissue damage after events such as myocardial infarction. Current strategies are aimed primarily at injury prevention, but attention has been increasingly targeted toward the development of regenerative therapies. This review focuses on recent developments in the field of cardiac fibroblast reprogramming into induced cardiomyocytes. Early efforts to produce cardiac regeneration centered around induced pluripotent stem cells, but clinical translation has proved elusive. Currently, techniques are being developed to directly transdifferentiate cardiac fibroblasts into induced cardiomyocytes. Viral vector‐driven expression of a combination of transcription factors including Gata4, Mef2c, and Tbx5 induced cardiomyocyte development in mice. Subsequent combinational modifications have extended these results to human cell lines and increased efficacy. The miRNAs including combinations of miR‐1, miR‐133, miR‐208, and miR‐499 can improve or independently drive regeneration of cardiomyocytes. Similar results could be obtained by combinations of small molecules with or without transcription factor or miRNA expression. The local tissue environment greatly impacts favorability for reprogramming. Modulation of signaling pathways, especially those mediated by VEGF and TGF‐&bgr;, enhance differentiation to cardiomyocytes. Current reprogramming strategies are not ready for clinical application, but recent breakthroughs promise regenerative cardiac therapies in the near future.

Electrocardiographic characteristics, antiarrhythmic utilization, and outcomes in patients with left ventricular assist devices

Left ventricular assist devices (LVAD) are an increasingly used therapy for patients with advanced heart failure. Arrhythmias are common complications following LVAD implantation requiring admission, initiation, and escalation of medical therapy. Despite their frequent use in the treatment of arrhythmias, little has been reported regarding electrocardiographic changes, antiarrhythmic utilization, and outcomes post-LVAD.

Depression and anxiety in patients undergoing left ventricular assist device implantation

Background: Depression and anxiety are associated with a worse prognosis in heart failure patients. The aim of this study was to identify the prevalence of depression and anxiety in left ventricular assist device (LVAD) candidates and assess their effect on post-LVAD outcomes. Methods: Based on the pre-LVAD psychological assessment, the total cohort of 246 patients were divided into 4 groups: 1) no depression or anxiety (NDep&Anx group, n = 138); 2) isolated depression (Dep group, n = 42); 3) isolated anxiety (Anx group, n = 32), and 4) combined depression and anxiety (Dep&Anx group, n = 34). Results: The Dep&Anx group was associated with higher prevalence of female gender (p = 0.03), higher body mass index (p = 0.03), elevated E/E’ (p = 0.003), and increased Model For End-Stage Liver Disease (MELD) XI score (p = 0.04) prior to LVAD as compared to the other 3 subgroups. The prevalence of other major psychiatric disorders (p = 0.03) and narcotic dependence (p = 0.004) was higher in the Dep&Anx group. Post-LVAD implantation, heart rate and filling pressures were elevated and readmission rate was higher (p = 0.001) in the Dep&Anx group. There was no difference in survival between the groups (p = 0.40, Log-Rank test). Conclusions: Pre-existing anxiety and depression was associated with worse HF pre- and post-LVAD implantation and higher readmissions rate after LVAD implantation.

Effect of Diltiazem on Exercise Capacity after Heart Transplantation

Sinus tachycardia (ST) is common after heart transplantation (HTx). The aim of the study was to evaluate the effect of diltiazem treatment during the first year after HTx on heart rate (HR), cardiac allograft function, and exercise capacity.