Faculty Bibliography

Background: Decreased peak oxygen consumption during exercise (peak Vo2) is a well-established prognostic marker for mortality in ambulatory heart failure. After heart transplantation, the utility of peak Vo2 as a marker of post-transplant survival is not well established.
Methods and Results: We performed a retrospective analysis of adult heart transplant recipients at the Hospital of the University of Pennsylvania who underwent cardiopulmonary exercise testing within a year of transplant between the years 2000 to 2011. Using time-to-event models, we analyzed the hazard of mortality over nearly two decades of follow-up as a function of post-transplant percent predicted peak Vo2 (%Vo2). A total of 235 patients met inclusion criteria. The median post-transplant %Vo2 was 49% (IQR 42 to 60). Each standard deviation (+/-14%) increase in %Vo2 was associated with a 32% decrease in mortality in adjusted models (HR 0.68, 95% CI 0.53 to 0.87, p = 0.002). A %Vo2 below 29%, 64% and 88% predicted less than 80% survival at 5, 10, and 15 years, respectively.
Conclusion(s): Post-transplant peak Vo2 is a highly significant prognostic marker for long-term post-transplant survival. It remains to be seen whether decreased peak Vo2 post-transplant is modifiable as a target to improve post-transplant longevity.
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Comprehensive information on the characteristics of surgical heart valves (SHVs) is essential for optimal valve selection. Such information is also important in assessing SHV function after valve replacement. Despite the existing regulatory framework for SHV sizing and labelling, this information is challenging to obtain in a uniform manner for various SHVs. To ensure that clinicians are adequately informed, the European Association for Cardio-Thoracic Surgery (EACTS), The Society of Thoracic Surgeons (STS) and American comprised of cardiac surgeons, cardiologists, engineers, regulatory bodies, representatives of the International Organization for Standardization and major valve manufacturers. Previously, the EACTS-STS-AATS Valve Labelling Task Force identified the most important problems around SHV sizing and labelling. This Expert Consensus Document formulates recommendations for providing SHV physical dimensions, intended implant position and hemodynamic performance in a transparent, uniform manner. Furthermore, the Task Force advocates for the introduction and use of a standardized chart to assess the probability of prosthesis-patient mismatch and calls valve manufacturers to provide essential information required for SHV choice on standardized Valve Charts, uniformly for all SHV models.
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PURPOSE/OBJECTIVE:Preoperative lymphoscintigraphy for sentinel lymph node mapping in melanoma improves the ability to locate nodes. However, it still remains unclear whether this step is required for all patients. METHODS:Patients diagnosed with cutaneous melanoma from 1996 to 2012 were identified. Exclusion criteria were in situ disease, metastatic disease, or no SLN biopsy. RESULTS:214 patients were evaluated. Median age was 57 years, the majority were male (59.8%), white (97.2%), and stage I (60.7%). SLN revealed metastatic disease in 14.5% of patients. The most common primary site was the trunk (43.4%) followed by head and neck (21%), upper extremity (19.2%), and lower extremity (16.4%). Multiple lymphatic basins were most common for head and neck lesions (66.7%) followed by those on the trunk (28.8%), with fewer identified when lower (11.4%), and upper extremities were involved (4.2%). When comparison was restricted to extremity vs. axial, a single basin was noted in 94.5% vs. 59.9% of patients, p < 0.0001. For all extremity lesions the SLN was located in the primary basin. Additional sites included in-transit (popliteal) and second tier basins. The only melanomas with bilateral or contralateral SLN were axial melanomas. CONCLUSIONS:Patients with axial melanomas benefit most from lymphoscintigraphy. This step may not be required for extremity melanoma.

BACKGROUND:Pharmacokinetically guided (PK-guided) versus body surface area-based 5-fluorouracil (5-FU) dosing results in higher response rates and better tolerability. A paucity of data exists on PK-guided 5-FU dosing in the community setting. PATIENTS AND METHODS/METHODS:Seventy colorectal cancer patients, from one academic and five community cancer centers, received the mFOLFOX6 regimen (5-FU 2,400 mg/m(2) over 46 hours every 2 weeks) with or without bevacizumab at cycle 1. The 5-FU continuous-infusion dose was adjusted for cycles 2-4 using a PK-guided algorithm to achieve a literature-based target area under the concentration-time curve (AUC). The primary objective was to demonstrate that PK-guided 5-FU dosing improves the ability to achieve a target AUC within four cycles of therapy. The secondary objective was to demonstrate reduced incidence of 5-FU-related toxicities. RESULTS:At cycles 1 and 4, 27.7% and 46.8% of patients achieved the target AUC (20-25 mg × hour/L), respectively (odds ratio [OR]: 2.20; p = .046). Significantly more patients were within range at cycle 4 compared with a literature rate of 20% (p < .0001). Patients had significantly higher odds of not being underdosed at cycle 4 versus cycle 1 (OR: 2.29; p = .037). The odds of a patient being within range increased by 30% at each subsequent cycle (OR: 1.30; p = .03). Less grade 3/4 mucositis and diarrhea were observed compared with historical data (1.9% vs 16% and 5.6% vs 12%, respectively); however, rates of grade 3/4 neutropenia were similar (33% vs 25%-50%). CONCLUSION/CONCLUSIONS:PK-guided 5-FU dosing resulted in significantly fewer underdosed patients and less gastrointestinal toxicity and allows for the application of personalized colorectal cancer therapy in the community setting.

OBJECTIVES: Coronary computed tomography angiography (CCTA) is often used to assess the extent and severity of atherosclerosis. A major limitation of CCTA are densely calcified coronary plaques that obscure the underlying lumen rendering assessment difficult. The purpose of this study was to evaluate the hemodynamic importance of densely calcified coronary lesions on CCTA in patients with low-to-intermediate likelihood of coronary artery disease. METHODS: We studied 92 patients (64+/-10 years, 75% men) who underwent CCTA and stress perfusion cardiovascular magnetic resonance (CMR). Coronary stenoses were categorized as none, less than 50%, 50-70%, and greater than 70%, or densely calcified. Coronary arteries were considered densely calcified if the artery had a calcified lesion obscuring the underlying lumen and did not have another stenosis of greater than 50%. CMR was considered abnormal if there was reversible ischemia or myocardial scar determined by the presence of late gadolinium enhancement. RESULTS: Among the 92 patients, 271 vessels were analyzed of which 44 (16%) were considered densely calcified. Among these 44 coronary territories, six (14%) had abnormal CMR findings. On a per-vessel analysis, a proportional increase in the number of myocardial segments with reversible ischemia or the presence of late gadolinium enhancement was associated with an increase of CCTA stenosis ranging from 2% in patients without coronary plaque to 70% in patients with a greater than 70% stenosis (P<0.0001). CONCLUSION: In conclusion, the vast majority (86%) of densely calcified lesions were not hemodynamically significant in our study. As our study was in patients with relatively low-to-intermediate likelihood of coronary artery disease, a prospective study is warranted to assess if our findings are generalizable to other patient populations.

Patients with coronary artery calcium (CAC) scores of zero are generally considered not to have atherosclerosis. Recent studies involving computed tomography coronary angiography (CTCA) challenge this assumption. This goal of the present study is to assess the frequency, morphology, location, and the prognosis of patients with plaque detected on CTCA and zero CAC. 1,119 patients (51 +/- 12 years, 52% male) with a zero CAC score during CTCA study were retrospectively identified. The CTCA studies were assessed for the presence, morphology, location and severity of all coronary plaques. All-cause mortality was assessed. The prevalence of coronary plaque was 13% (147 patients). Among the 212 plaques identified 154 (73%) were non-calcified, 28 (13%) were calcified, and 30 (14%) were of mixed morphology. Notably, >/=70% stenosis was noted among only 0.4% of all patients. ROC analysis revealed that coronary artery disease risk factors did not add to the prediction of plaque among our patients. Over a mean follow-up of 2.5 +/- 0.6 years there were 4 deaths (0.4%), all in patients without coronary plaque on CTCA. The presence of coronary plaque is not uncommon among patients with zero CAC scores. These plaques were rarely associated with hemodynamically significant stenoses and were associated with an excellent prognosis. Clinical factors do not appear to be useful in predicting which patients with zero CAC scores have undetected coronary plaque

Triple-rule-out computed tomographic angiography (TRO CTA), performed to evaluate the coronary arteries, pulmonary arteries, and thoracic aorta, has been associated with high radiation exposure. The use of sequential scanning for coronary computed tomographic angiography reduces the radiation dose. The application of sequential scanning to TRO CTA is much less well defined. We analyzed the radiation dose and image quality from TRO CTA performed at a single outpatient center, comparing the scans from a period during which helical scanning with electrocardiographically controlled tube current modulation was used for all patients (n = 35) and after adoption of a strategy incorporating sequential scanning whenever appropriate (n = 35). Sequential scanning was able to be used for 86% of the cases. The sequential-if-appropriate strategy, compared to the helical-only strategy, was associated with a 61.6% dose decrease (mean dose-length product of 439 mGy x cm vs 1,144 mGy x cm and mean effective dose of 7.5 mSv vs 19.4 mSv, respectively, p <0.0001). Similarly, a 71.5% dose reduction occurred among the 30 patients scanned with the sequential protocol compared to the 40 patients scanned with the helical protocol using either strategy (326 mGy x cm vs 1,141 mGy x cm and 5.5 mSv vs 19.4 mSv, respectively, p <0.0001). Although the image quality did not differ between the strategies, a nonstatistically significant trend was seen toward better quality in the sequential protocol than in the helical protocol. In conclusion, approaching TRO CTA with a diagnostic strategy of sequential scanning, as appropriate, can offer a marked reduction in the radiation dose while maintaining the image quality

BACKGROUND: Normal exercise single-photon emission computed tomography (SPECT) studies are associated with a low event rate (<1.0%/year) during short-term follow-up. The influence of cardiac risk factors on long-term outcomes in such patients has not been well studied. MATERIAL AND METHODS: 2,597 patients (55 +/- 12 years, male 41%) without a history of heart disease and a normal exercise SPECT between the years 1995 and 2006 were followed for a mean 6.8 +/- 3.1 years for all-cause mortality assessed for using the Social Security Death Index. Baseline clinical risk factors and other clinical information were recorded for each patient and compared to outcomes. RESULTS: The mortality rate was 0.9%/year for our overall study population but varied according to individual baseline risk factors. Three coronary artery disease (CAD) risk factors were significant predictors of all-cause mortality: hypertension, diabetes, and smoking. When all three were absent, long-term all-cause mortality rate averaged 0.2%/year and when all three were present, all-cause mortality averaged 1.8%/year, constituting a 5.7-fold adjusted increase in risk (95% CI 2.7-12.8, P < .0001). CONCLUSIONS: During follow-up, annualized mortality rate varies markedly according to the number of CAD risk factors in patients without known heart disease and a normal exercise SPECT stress. Despite overall excellent long-term prognosis of a normal exercise SPECT, the burden of traditional CAD risk factors exert a strong synergistic influence on long-term survival and warrant aggressive treatment in this patient population