James D. Flaherty

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.

Acute Heart Failure Syndromes in Patients With Coronary Artery Disease : Early Assessment and Treatment

Acute heart failure syndromes (AHFS) have emerged as a leading public health problem worldwide, accounting for a substantial number of hospitalizations and a high utilization of resources. Although in-hospital mortality rates are relatively low, patients with AHFS have very high early after-discharge mortality and rehospitalization rates. The majority of patients admitted with AHFS have coronary artery disease (CAD), which independently has an adverse impact on prognosis. The initial in-hospital and after-discharge management of AHFS may be dependent on clinical presentation: AHFS in patients with underlying CAD or acute coronary syndromes (ACS) complicated by heart failure. In addition, the extent and severity of CAD and the presence of ischemia and/or stunned/hibernating myocardium should be assessed for optimal management. Although the overall management of AHFS with CAD may be similar to that in patients with ACS complicated by heart failure, for which specific guidelines exist, management of the former is less well defined. Prospective studies of the assessment and treatment of CAD in patients with AHFS are urgently needed.

Saccular aneurysm induction by elastase digestion of the arterial wall: A new animal model

OBJECTIVE To develop a rabbit aneurysm model that is more realistic in gross appearance and histological features than previous models and to enable the development of a larger animal model. METHODS Ten rabbits received porcine pancreatic elastase, five at the right common carotid artery bifurcation and five others at the right superior thyroid artery origin. One control animal received collagenase and another received papaverine, each at the right superior thyroid artery origin. The agents were topically delivered to the arterial adventitia with a microsyringe after surgical exposure of the targeted arteries. The arteries were monitored for aneurysm growth with a video camera for up to 3 hours and were then removed and processed for histology. RESULTS Saccular aneurysms developed in one of five animals after elastase application at the carotid bifurcation and in all five animals receiving elastase at the superior thyroid artery origin. Among the six aneurysms, recurrent minor hemorrhages occurred in four, thrombosis of the aneurysm sac in three, and rupture causing severe bleeding in one. Histological sections revealed thin-walled aneurysms composed only of collagen fibers and some cellular elements. No saccular dilation resulted from papaverine application. Collagenase application resulted in a hemorrhagic-thrombotic lesion in the arterial wall but no aneurysm formation. CONCLUSION Arterial saccular aneurysms were induced in rabbits by topical application of elastase with an easy and efficient method. These aneurysms are histologically similar to natural aneurysms, and their arterial nature renders them more authentic than those of surgical models. This aneurysm model may serve as a foundation for further aneurysm research.

Predictive Value of Stress Myocardial Perfusion Imaging in Liver Transplant Candidates

In summary, these data indicate that SPECT imaging has a poor predictive value for CAD in OLT candidates. Coronary angiography has a primary screening role for this population, especially in patients with multiple cardiac risk factors or a known history of CAD.

Predictive Value of Dobutamine Stress Echocardiography for Coronary Artery Disease Detection in Liver Transplant Candidates

Patients with obstructive coronary artery disease (CAD) undergoing orthotopic liver transplantation (OLT) are at increased risk of poor outcomes. The accuracy of dobutamine stress echocardiography (DSE) to detect obstructive CAD is not well established in this population. We retrospectively identified patients with end‐stage liver disease who underwent both DSE and coronary angiography as part of risk stratification prior to OLT. One hundred and five patients had both DSE and angiography, of whom 14 had known CAD and 27 failed to reach target heart rate during DSE. Among the remaining 64 patients (45 men; average age 61 ± 8 years) DSE had a low sensitivity (13%), high specificity (85%), low positive predictive value (PPV) (22%) and intermediate negative predictive value (NPV) (75%) for obstructive CAD. DSE as a screening test for obstructive CAD in OLT candidates has a poor sensitivity. The frequent chronotropic incompetence and low sensitivity in patients who achieve target heart rate, even in those with multiple cardiovascular disease risk factors, suggest that alternative or additional methods of risk stratification are necessary.

Drug-Eluting Versus Bare-Metal Stents in Unprotected Left Main Coronary Artery Stenosis: A Meta-Analysis

OBJECTIVES We undertook a meta-analysis to assess outcomes for drug-eluting stents (DES) and bare-metal stents (BMS) in percutaneous coronary intervention for unprotected left main coronary artery (ULMCA) stenosis. BACKGROUND Uncertainty exists regarding the relative performance of DES versus BMS in percutaneous coronary intervention for unprotected left main coronary stenosis. METHODS Of a total of 838 studies, 44 met inclusion criteria (n = 10,342). The co-primary end points were mortality, myocardial infarction (MI), target vessel/lesion revascularization (TVR/TLR), and major adverse cardiac events (MACE: mortality, MI, TVR/TLR). RESULTS Event rates for DES and BMS were calculated at 6 to 12 months, at 2 years, and at 3 years. Crude event rates at 3 years were mortality (8.8% and 12.7%), MI (4.0% and 3.4%), TVR/TLR (8.0% and 16.4%), and MACE (21.4% and 31.6%). Nine studies were included in a comparative analysis (n = 5,081). At 6 to 12 months the adjusted odds ratio (OR) for DES versus BMS were: mortality 0.94 (95% confidence interval [CI]: 0.06 to 15.48; p = 0.97), MI 0.64 (95% CI: 0.19 to 2.17; p = 0.47), TVR/TLR 0.10 (95% CI: 0.01 to 0.84; p = 0.01), and MACE 0.34 (95% CI: 0.15 to 0.78; p = 0.01). At 2 years, the OR for DES versus BMS were: mortality 0.42 (95% CI: 0.28 to 0.62; p < 0.01), MI 0.16 (95% CI: 0.01 to 3.53; p = 0.13), and MACE 0.31 (95% CI: 0.15 to 0.66; p < 0.01). At 3 years, the OR for DES versus BMS were: mortality 0.70 (95% CI: 0.53 to 0.92; p = 0.01), MI 0.49 (95% CI: 0.26 to 0.92; p = 0.03), TVR/TLR 0.46 (95% CI: 0.30 to 0.69; p < 0.01), and MACE 0.78 (95% CI: 0.57 to 1.07; p = 0.12). CONCLUSIONS Our meta-analysis suggests that DES is associated with favorable outcomes for mortality, MI, TVR/TLR, and MACE as compared to BMS in percutaneous coronary intervention for unprotected left main coronary artery stenosis.

Influence of coronary artery disease and coronary revascularization status on outcomes in patients with acute heart failure syndromes: A report from OPTIMIZE‐HF (Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure)*

Coronary artery disease (CAD) is frequent among patients hospitalized with acute heart failure syndromes (AHFS).

Fatal Case of Endocarditis Due to Weissella confusa

ABSTRACT This is the first reported case of endocarditis due to the Lactobacillus-like vancomycin-resistant gram-positive bacillus Weissella confusa. Full identification and susceptibility testing of Lactobacillus-like organisms recovered in blood culture should be performed for patients with clinical presentations that suggest endocarditis.

Antirestenotic Effects of a Locally Delivered Caspase Inhibitor in a Balloon Injury Model

Background—The precise role of arterial barotrauma-mediated apoptosis in causing restenosis is unclear. The purpose of this study was to determine if a link exists between angioplasty-mediated medial smooth muscle cell apoptosis and subsequent neointimal hyperplasia. Methods and Results—Bilateral iliac artery angioplasty was performed in 25 male New Zealand White rabbits. Simultaneous with balloon injury, each artery was treated locally with either the caspase inhibitor N-benzyloxycarbonyl-Val-Ala-Asp(Ome)-fluoromethylketone (ZVAD-fmk) or control. In the acute cohort that was survived to 4 hours (n=10, 7 high dose and 3 low dose), an apoptotic index was calculated using the terminal deoxynucleotidyl TUNEL method. In the intermediate cohort that was survived to 2 weeks (n=5), luminal reendothelialization was measured via CD-31 staining. In the chronic cohort that was survived to 4 weeks (n=10), neointimal area was measured. In the acute cohort, there was a 40% reduction in the apoptotic index with high-dose ZVAD-fmk (P =0.008) and a 33% reduction with low-dose ZVAD-fmk (P =0.08). At 2 weeks, there was no significant difference in the degree of luminal reendothelialization. However, at 4 weeks, there was a 33% (0.33±0.23 versus 0.22±0.20 mm2) (P <0.005) reduction in neointimal area in ZVAD-fmk–treated arteries. Conclusions—The local delivery of ZVAD-fmk during balloon injury inhibits smooth muscle cell apoptosis. This corresponds to a significant reduction in neointimal proliferation seen at 4 weeks without a significant change in the degree of reendothelialization at 2 weeks.

Coronary multidetector computed tomographic angiography to evaluate coronary artery disease in liver transplant candidates: methods, feasibility and initial experience.

Aims In patients undergoing orthotopic liver transplantation (OLT), coronary artery disease (CAD), obstructive and nonobstructive, is associated with high morbidity and mortality. In OLT candidates, stress testing for detecting ischemia is often inaccurate, and this patient population often has relative contraindications for cardiac catheterization. The objective of this study was to describe the methods, assess the feasibility and determine the extent and severity of CAD in OLT candidates without a prior history of CAD using coronary multidetector computer tomographic angiography (MDCTA). Methods Sixty-five OLT candidates without known CAD underwent coronary MDCTA with dual source cardiac computed tomography (Siemens Definition). Coronary arteries were divided into 17 segments based on American Heart Association guidelines and evaluated independently by two blinded reviewers. Image quality of coronary MDCTA was assessed on a four-point Likert scale (0 = poor, 1 = fair, 2 = good, and 3 = excellent). Atherosclerotic lesions were evaluated for severity [mild (0–50%), moderate (51–70%), and severe (71–100%)], morphology, extent, location and consistency. Results Image quality was graded as good or excellent in 73.8%. In this cohort of OLT candidates without known CAD, 9% had normal coronary arteries, 58% had mild CAD and 34% had moderate to severe CAD. Plaque severity and burden scores were high. Conclusion The prevalence of asymptomatic CAD is high in OLT candidates. Coronary MDCTA is feasible in OLT candidates and appears to be a useful technique to diagnose occult CAD in this patient population.