Cardiovascular risk assessment of the liver transplant candidate.

Liver transplantation (LT) candidates today are increasingly older, have greater medical acuity, and have more cardiovascular comorbidities than ever before. Steadily rising model for end-stage liver disease (MELD) scores at the time of transplant, resulting from high organ demand, reflect the escalating risk profiles of LT candidates. In addition to advanced age and the presence of comorbidities, there are specific cardiovascular responses in cirrhosis that can be detrimental to the LT candidate. Patients with cirrhosis requiring LT usually demonstrate increased cardiac output and a compromised ventricular response to stress, a condition termed cirrhotic cardiomyopathy. These cardiac disturbances are likely mediated by decreased beta-agonist transduction, increased circulating inflammatory mediators with cardiodepressant properties, and repolarization changes. Low systemic vascular resistance and bradycardia are also commonly seen in cirrhosis and can be aggravated by beta-blocker use. These physiologic changes all contribute to the potential for cardiovascular complications, particularly with the altered hemodynamic stresses that LT patients face in the immediate post-operative period. Post-transplant reperfusion may result in cardiac death due to a multitude of causes, including arrhythmia, acute heart failure, and myocardial infarction. Recognizing the hemodynamic challenges encountered by LT patients in the perioperative period and how these responses can be exacerbated by underlying cardiac pathology is critical in developing recommendations for the pre-operative risk assessment and management of these patients. The following provides a review of the cardiovascular challenges in LT candidates, as well as evidence-based recommendations for their evaluation and management.

Off-label use of drug-eluting versus bare metal stents: a lesion-specific systematic review of long-term outcomes.

OBJECTIVE: The purpose of this systematic review was to evaluate differences in lesion-specific outcomes with the "off-label" use of drug-eluting stents (DES) versus bare metal stents (BMS). METHODS: MEDLINE, PubMed, the Cochrane databases, and other Web were searched for studies evaluating off-label use of DES and BMS with the same characteristics. Of 1,258 abstracts or manuscripts reviewed, 112 studies were included (total N = 23,438). Studies were excluded if patients received both types of stent or no stent; lesion type was unknown; lesion-specific outcomes for ≥6 months were unavailable; or <25 patients were enrolled. RESULTS: Overall mortality at 6-12 months was approximately 3% for BMS and DES for off-label use. Increase in mortality was greater from 6-12 months to 2 years with BMS than with DES (3.3%-9.1%; 2.8%-4.1%); however, rates were similar at 3 years (BMS: 18.8%; DES:15.3%). Myocardial Infarction rates were similar for both types at 6-12 months (BMS: 6.5%; DES: 6.0%). Overall rates of stent thrombosis were 1.8% and 1.7% for BMS and DES, respectively. Similar or slightly lower rates of stent thrombosis were seen for most lesion types, except higher rates for small vessels for BMS (5.2%) and true bifurcation for DES (3.3%). Rates of target lesion revascularization (TLR) were 7.5% for BMS and 19.6% for DES at 6-12 months. At 2-years TLR remained lower than DES. When the combined group was compared to registry data alone, similar values were seen. CONCLUSIONS: Rates of mortality, myocardial infarction (MI), and stent thrombosis were similar in patients receiving BMS or DES, while TLR rates were lower in DES patients.

Acute heart failure syndromes and coronary perfusion.

Acute heart failure syndromes (AHFS), with a high post-discharge mortality and rehospitalization rate, represent a significant public health burden. The treatment of patients hospitalized with AHFS often includes the use of vasoactive medications such as inotropes and vasodilators. Although such agents are frequently used, their safety and efficacy remain controversial. A significant number of patients with heart failure have underlying coronary artery disease and may be at greater risk from hemodynamic alterations that can diminish coronary perfusion. In AHFS, the relationship among vasoactive medications, coronary perfusion, and potential myocardial injury needs further investigation. Newer techniques now available to evaluate coronary perfusion should provide guidance for the evaluation of existing and future vasoactive therapies for AHFS.

Contrast media: procedural capacities and potential risks.

Contrast media are known to have transient hemodynamic properties that can influence a patient's clinical status, including heart rate variability and blood pressure. These changes have the potential to impact the diagnostic quality of CT scans. Although most patients are able to receive contrast media without significant adverse reactions, events occur in a minority of cases. These reactions range from mild discomfort (injection-associated pain and heat sensation) to more significant cardiac, renal, and hypersensitivity reactions. The incidence of adverse reactions varies with the type of contrast media used, and several randomized trials have elucidated the cardiac and renal differences among agents. Risk factors for contrast-induced acute kidney injury (CIAKI) have been established, with baseline kidney disease amplified by the presence of diabetes constituting the highest-risk patient group. Strategies for preventing CIAKI include antioxidant therapy, hydration regimens, and choice of contrast agents. Enhanced knowledge on the part of physicians and medical personnel regarding the properties and potential side effects of iodinated contrast agents should lead to improved patient safety and efficacy when performing radiologic examinations.

Granulocyte-colony stimulating factor administration after myocardial infarction in a porcine ischemia-reperfusion model: functional and pathological effects of dose timing.

BACKGROUND: Acute MI results in cardiomyocyte death, left ventricular (LV) dysfunction and adverse remodeling. The use of growth factors may prevent this. The aim of this study was to assess early and delayed administration of granulocyte colony-stimulating factor (G-CSF) in a porcine model of myocardial infarction (MI) and reperfusion. METHODS: MI was induced by balloon occlusion followed by reperfusion. There were 3 groups: Control (n = 11), Early (n = 17), and Delayed treatment (n = 8). The Early group received G-CSF 10 microg/kg/d every other day for 20 days beginning immediately. The Delayed group received G-CSF 10 microg/kg/d daily for 10 days beginning on day 5. Magnetic resonance imaging was performed on days 5 and 56. LV end-diastolic volumes (EDV), end-systolic volumes, ejection fraction, expansion index, sphericity index, thinning ratio, and infarct mass were calculated. Histology was analyzed at 56 days. RESULTS: At 56 days the change in EDV was 53% less in the Early (p = 0.005) and 24% greater in the Delayed (p = NS) group versus Control. The Delayed group also showed a 60% increase in normalized infarct mass (p = 0.055) and an 88% increase in expansion index (p = 0.003). Both groups had significantly less capillary density in the infarct border zone. The Delayed also had decreased arteriolar density in the mid scar. CONCLUSIONS: Early treatment with G-CSF after MI decreases ventricular dilatation, while delayed treatment has a deleterious effect on LV remodeling. This may be related to changes in myocardial vascularity. The effects of G-CSF therapy and its dose timing help to elucidate the results of recent human trials.

Recent clinical trials of iodixanol.

In patients with well-preserved renal function, the choice of contrast agent appears to have little impact on the development of contrast-induced nephropathy (CIN). However, in patients with underlying renal insufficiency and diabetes mellitus, it has been shown that the use of low-osmolar media is associated with a lower incidence of CIN compared with high-osmolar agents. Previously, it was unknown whether further benefit would be derived from the use of iso-osmolar contrast media. Recent studies, including Nephrotoxicity in High-Risk Patients Study of Iso-osmolar and Low-Osmolar Nonionic Contrast Media (NEPHRIC), have shown a reduction in the incidence of CIN with the iso-osmolar contrast agent iodixanol compared with low-osmolar agents in patients with renal insufficiency and diabetes. The peak rise in serum creatinine was significantly reduced with iodixanol (0.13 mg/dL vs 0.55 mg/dL, P <.001). The incidence of CIN, defined as a peak rise > 0.5 mg/dL, was decreased from 26% to 3%, P <.0002 when iodixanol was used. An ongoing, multicenter, prospective, double-blind, randomized study (Visipaque Angiography/Interventions with Laboratory Outcomes for Renal Insufficiency [VALOR]) is evaluating the potential benefit of iodixanol in reducing CIN in patients with preexisting renal impairment. Accumulating evidence suggests that the use of iso-osmolar contrast agents in conjunction with other proven measures, especially adequate intravenous hydration and contrast dosage limitation, can reduce the morbidity and mortality associated with CIN. These measures have the potential for a significant reduction in health care costs.