New therapy, new challenges: The effects of long-term continuous flow left ventricular assist device on inflammation.

Surgically implanted continuous flow left ventricular assist devices (CF-LVADs) are currently used in patients with end-stage heart failure (HF). However, CF-LVAD therapy introduces a new set of complications and adverse events in these patients. Major adverse events with the CF-LVAD include right heart failure, vascular dysfunction, stroke, hepatic failure, and multi-organ failure, complications that may have inflammation as a common etiology. Our aim was to review the current evidence showing a relationship between these adverse events and elevated levels of inflammatory biomarkers in CF-LVAD recipients.

Increased cyclic guanosine monophosphate levels and continuous-flow left-ventricular assist devices: Implications for gastrointestinal bleeding.

OBJECTIVES: We examine the hypothesis that cyclic guanosine monophosphate (cGMP) levels are elevated in recipients of continuous-flow left ventricular assist devices (CF-LVADs) and that elevated cGMP levels are associated with a risk of gastrointestinal (GI) bleeding events. METHODS: The levels of cGMP, nitric oxide, platelet activation markers, platelet-derived growth factors (PDGF) AB/BB and AA, and the inflammatory mediator C-reactive protein (CRP) were examined in 19 CF-LVAD recipients, 21 patients who had heart failure, and 19 healthy control-group participants. RESULTS: The median level of cGMP was significantly higher in CF-LVAD recipients, compared with healthy participants (6.6 vs 2.1 pmol/mL, u = 62.5; P = .001; r = -0.55). Median cGMP levels in the heart failure group (12.5 pmol/L) were higher, compared with both CF-LVAD recipients (u = 75.0; P = .001; r = -0.53) and healthy participants (u = 4.0; P < .001; r = -0.83). Compared with the healthy group, median CRP levels were significantly higher in CF-LVAD recipients (2.9 vs 8.0 mg/L; u = 58.0; P < .001; r = -0.63) and heart failure patients (2.9 vs 7.0 mg/L; u = 59.0; P < .001; r = -0.65). In the subgroup of patients supported with the HeartMate II (Thoratec Corporation, Pleasanton, Calif), pulsatility index was significantly negatively correlated with cGMP levels (r = -0.73; P < .05), indicating that low pulsatility index is associated with higher cGMP levels. High cGMP levels were significantly associated with GI bleeding events, but not with bleeding events in general. CONCLUSIONS: The primary finding of this study is that GI bleeding in CF-LVAD recipients is associated with significantly elevated cGMP levels, despite high levels of CRP, which interfere with cGMP production. Further studies are required to determine whether elevated cGMP levels can be used as a clinical marker for increased risk of GI bleeding in CF-LVAD recipients.

TLR4 Expression Is Associated with Left Ventricular Dysfunction in Patients Undergoing Coronary Artery Bypass Surgery.

INTRODUCTION: Toll-like receptor 4 (TLR4) is an innate immune receptor expressed in immune cells and the heart. Activation of the immune system following myocardial ischemia causes the release of proinflammatory mediators that may negatively influence heart function. AIM: The aim of this study is to determine whether TLR4 is activated in peripheral monocytes and heart tissue taken from patients with varying degrees of myocardial dysfunction caused by coronary artery diseases and scheduled for coronary artery bypass graft (CABG) surgery before 12 months following operation. METHODS AND RESULTS: Patients (n = 44) undergoing CABG surgery having left ventricular ejection fraction ≤ 45% ('reduced EF', n = 20) were compared to patients with preserved EF >45% ('preserved EF' group, n = 24). 'Reduced EF' patients exhibited increased TLR4 expression in monocytes (2.78±0.49 vs. 1.76±0.07 rMFI, p = 0.03). Plasma levels of C-reactive protein, microRNA miR-320a, brain natriuretic peptide (pro BNP) and NADPH oxidase (NOX4) were also significantly different between the 'preserved EF' and 'reduced EF'groups. Elevated TLR4 gene expression levels in the right auricle correlated with those of EF (p<0.008), NOX4 (p<0.008) and miR320, (p<0.04). In contrast, no differences were observed in peripheral monocyte TLR2 expression. After CABG surgery, monocyte TLR4 expression decreased in all patients, reaching statistical significance in the 'reduced EF' group. CONCLUSION: TLR4 is activated in peripheral monocytes and heart tissue obtained from patients with ischemic heart disease and reduced left ventricular function. Coronary revascularization decreases TLR4 expression. We therefore propose that TLR4 plays a pathogenic role and may serve as an additional marker of ischemic myocardial dysfunction.

Longitudinal assessment of inflammation in recipients of continuous-flow left ventricular assist devices.

BACKGROUND: The long-term effects of continuous-flow left ventricular assist device (CF-LVAD) support on trends of inflammatory markers over time are unknown. We examined the hypothesis that the levels of inflammatory markers in CF-LVAD recipients are higher than in healthy controls and that these levels increase over time with long-term CF-LVAD support. METHODS: We examined the levels of inflammatory markers longitudinally at baseline before CF-LVAD implantation and at 3, 6, and 9 months after implantation. We then compared the levels of inflammatory markers to those in a healthy control group. RESULTS: Compared with baseline values before CF-LVAD implantation, left ventricular end-diastolic diameter (LVEDd) and left ventricular end-systolic diameter (LVESd) decreased significantly at 3, 6, and 9 months after CF-LVAD implantation. Brain natriuretic peptide (BNP) levels dropped significantly after CF-LVAD implantation but did not normalize. Improvements in ejection fraction at 3, 6, and 9 months after CF-LVAD implantation did not reach significance. Monocyte chemoattractant protein-1, interferon γ-induced protein, and C-reactive protein levels were higher in the CF-LVAD recipients at each of the time points (baseline before CF-LVAD implantation and 3, 6, and 9 months after implantation) compared with levels in healthy controls. In CF-LVAD recipients, serum interleukin-8, tumour necrosis factor-α, and macrophage inflammatory protein-ß increased significantly at 9 months, and macrophage-derived chemokine increased at 6 months after CF-LVAD implantation compared with baseline. CONCLUSIONS: Despite improvements in LV dimensions and BNP levels, markers of inflammation remained higher in CF-LVAD recipients. High levels of inflammation in CF-LVAD recipients may result from heart failure preconditioning or the long-term device support, or both. Because inflammation may be detrimental to CF-LVAD recipients, future studies should determine whether inflammatory pathways are reversible.

Tricuspid valve replacement: the effect of gender on operative results.

BACKGROUND AND AIM OF THE STUDY: Tricuspid valve replacement (TVR) is considered a high-risk operation. The study aim was to analyze the authors' eight-year experience with TVR and to characterize the specific risk factors for this operation. METHODS: Between January 2005 and August 2012, a total of 67 patients (46 females, 21 males; mean age 58 +/- 14 years; range: 25-86 years) underwent TVR at the authors' center. Re-do operations were performed in 48 patients (72%), including 37 patients (55%) who had at least two previous surgeries. Isolated TVR was performed in 28 patients (42%). The follow up (mean 28 months) included echocardiography and survival analysis. RESULTS: The overall operative mortality was 17.9% (n = 12, all female). In the latter half of the study period, mortality declined to 11.4% (p = NS). Major postoperative morbidity included prolonged mechanical ventilation (28.4%), low cardiac output (29.8%), and acute renal failure requiring hemodialysis (10.4%). Univariate analysis revealed that female gender (p = 0.007), NYHA class (p = 0.038), serum bilirubin level (p = 0.02) and number of previous cardiac surgeries (p = 0.05) were associated with increased operative mortality. Multivariable analysis demonstrated that reoperation (OR 6.06, p = 0.036) was an independent risk factor for operative mortality or complications. Echocardiography at follow up showed that 92.6% of all patients had tricuspid regurgitation grade < 2. The overall five-year survival rates for males and females were 82% and 53%, respectively (p = 0.03), but five-year survival for operative survivors was similar in males and females (82% versus 73%, p = 0.5). Cox regression analysis showed that age (OR 1.07, p = 0.028) and reoperation (OR 6.1, p = 0.038) were independent risk factors for late mortality. CONCLUSION: TVR remains a high-risk operation, particularly for advanced age and previously operated patients; however, the long-term survival is satisfactory. Typically, women undergo TVR at an older age with a higher mortality rate than men. However, the long-term mortality rate of patients who survived surgery was not associated with gender.

Primary cardiac valve tumors.

To assess the prevalence, characteristics, and outcome of surgical treatment of primary cardiac valve tumors in a single center, we reviewed our experience in 6 women and 1 man, aged 49 to 76 years (mean, 64.7 years) who presented between 1999 and 2006. In one patient, the diagnosis of cardiac valve tumor was made incidentally on transesophageal echocardiography during aortocoronary bypass surgery. The others had clinical symptoms: angina or myocardial infarction in 3, congestive heart failure in 2, dyspnea and cerebrovascular ischemia in 1 patient each. Four of the 7 tumors were benign, and 3 were malignant. All patients survived the operation and recovered uneventfully. Midterm follow-up was available in all patients. Two patients with malignant tumors were considered unsuitable for adjuvant therapy by the oncologist; both died during follow-up from local tumor recurrence. All 5 survivors were categorized at the last follow-up as functional class I, with normal exercise tolerance. Excellent early and midterm surgical results can be obtained in patients with benign cardiac valve tumors, but the prognosis for those with a malignant tumor is poor.

Video-assisted pericardial fenestration for effusions after cardiac surgery.

Delayed-onset pericardial effusion following cardiac surgery can give rise to significant morbidity due to its presentation as well as management by traditional surgical techniques. An institutional experience of a video-assisted thoracoscopic technique to create a pericardial window, with the advantages of a minimally invasive approach combined with excellent visualization in such patients, was reviewed. A retrospective analysis was conducted on all patients undergoing video-assisted thoracoscopic for delayed pericardial effusion after cardiac surgery from January 2001 to January 2006 at our center. Seven patients with echocardiographically diagnosed delayed tamponade underwent video-assisted thoracoscopy; 5 were receiving anticoagulants after valve replacement, and 2 had undergone heart transplantation. Pericardial windows were created under general anesthesia and single-lung ventilation using 2 to 3 trocars. Mean operative time was 45 min. There were no complications of the thoracoscopic technique. Video-assisted thoracoscopic creation of a pericardial window is safe and effective treatment for loculated pericardial effusions secondary to cardiac surgery.