SERCA2a Agonist Effects on Cardiac Performance During Exercise in Heart Failure With Preserved Ejection Fraction.

BACKGROUND: Impaired ventricular relaxation influences left ventricular pressures during exercise in heart failure with preserved ejection fraction (HFpEF). Sarco/endoplasmic reticulum calcium-adenosine triphosphatase (SERCA2a) facilitates myocardial relaxation by increasing calcium reuptake and is impaired in HFpEF. OBJECTIVES: This study sought to investigate the effects of istaroxime, a SERCA2 agonist, on lusitropic and hemodynamic function during exercise in patients with HFpEF and control subjects. METHODS: Eleven control subjects (7 male, 4 female) and 15 patients with HFpEF (8 male, 7 female) performed upright cycle exercise with right-sided heart catheterization. Participants received istaroxime (0.5 µg/kg/min) or saline placebo (single-blind, crossover design). Cardiac output, pulmonary capillary wedge pressure (PCWP), and diastolic function were measured at rest and during submaximal exercise. In an exploratory analysis (Hedge's g), 7 patients with HFpEF received higher-dose istaroxime (1.0 µg/kg/min). End-systolic elastance (Ees) was calculated by dividing systolic blood pressure (SBP) × 0.9 by end-systolic volume (ESV) (on 3-dimensional echocardiography). RESULTS: Patients with HFpEF had higher PCWP (25 ± 10 mm Hg vs 12 ± 5 mm Hg; P < 0.001) and lower tissue Doppler velocities during exercise. Istaroxime (0.5 µg/kg/min) had no effect on resting or exercise measures in patients with HFpEF or control subjects. Control subjects had a larger increase in Ees (Δ 1.55 ± 0.99 mm Hg/mL vs Δ 0.86 ± 1.31 mm Hg/mL; P = 0.03), driven by lower ESV. Comparing placebo and istaroxime 1.0 µg/kg/min during exercise, PCWP during the 1.0 µg/kg/min istaroxime dose was slightly lower (Δ 2.2 mm Hg; Hedge's g = 0.30). There were no effects on diastolic function, but there were increases in SBP and s', suggesting a mild inotropic effect. CONCLUSIONS: Low-dose istaroxime had no effect on cardiac filling pressure or parameters of relaxation in patients with HFpEF during exercise. Higher doses of istaroxime may have been more effective in reducing exercise PCWP in patients with HFpEF. (Hemodynamic Response to Exercise in HFpEF Patients After Upregulation of SERCA2a; NCT02772068).

One-Year Committed Exercise Training Reverses Abnormal Left Ventricular Myocardial Stiffness in Patients With Stage B Heart Failure With Preserved Ejection Fraction.

BACKGROUND: Individuals with left ventricular (LV) hypertrophy and elevated cardiac biomarkers in middle age are at increased risk for the development of heart failure with preserved ejection fraction. Prolonged exercise training reverses the LV stiffening associated with healthy but sedentary aging; however, whether it can also normalize LV myocardial stiffness in patients at high risk for heart failure with preserved ejection fraction is unknown. In a prospective, randomized controlled trial, we hypothesized that 1-year prolonged exercise training would reduce LV myocardial stiffness in patients with LV hypertrophy. METHODS: Forty-six patients with LV hypertrophy (LV septum >11 mm) and elevated cardiac biomarkers (N-terminal pro-B-type natriuretic peptide [>40 pg/mL] or high-sensitivity troponin T [>0.6 pg/mL]) were randomly assigned to either 1 year of high-intensity exercise training (n=30) or attention control (n=16). Right-heart catheterization and 3-dimensional echocardiography were performed while preload was manipulated using both lower body negative pressure and rapid saline infusion to define the LV end-diastolic pressure-volume relationship. A constant representing LV myocardial stiffness was calculated from the following: P=S×[Exp {a (V-V0)}-1], where "P" is transmural pressure (pulmonary capillary wedge pressure - right atrial pressure), "S" is the pressure asymptote of the curve, "V" is the LV end-diastolic volume index, "V0" is equilibrium volume, and "a" is the constant that characterizes LV myocardial stiffness. RESULTS: Thirty-one participants (exercise group [n=20]: 54±6 years, 65% male; and controls (n=11): 51±6 years, 55% male) completed the study. One year of exercise training increased max by 21% (baseline 26.0±5.3 to 1 year later 31.3±5.8 mL·min-1·kg-1, P<0.0001, interaction P=0.0004), whereas there was no significant change in max in controls (baseline 24.6±3.4 to 1 year later 24.2±4.1 mL·min-1·kg-1, P=0.986). LV myocardial stiffness was reduced (right and downward shift in the end-diastolic pressure-volume relationship; LV myocardial stiffness: baseline 0.062±0.020 to 1 year later 0.031±0.009), whereas there was no significant change in controls (baseline 0.061±0.033 to 1 year later 0.066±0.031, interaction P=0.001). CONCLUSIONS: In patients with LV hypertrophy and elevated cardiac biomarkers (stage B heart failure with preserved ejection fraction), 1 year of exercise training reduced LV myocardial stiffness. Thus, exercise training may provide protection against the future risk of heart failure with preserved ejection fraction in such patients. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03476785.

Impact of severe obesity on exercise performance in heart failure with preserved ejection fraction.

BACKGROUND: Obesity plays an important role in functional impairment in HFpEF. The mechanisms underlying decreased functional capacity in obese HFpEF are not clear. We assessed the cardiac and peripheral determinants of exercise performance in HFpEF patients with class 2 obesity in the upright position, representative of posture when performing functional activities. METHODS AND RESULTS: Thirty-two HFpEF patients were divided into two groups by presence of class 2 obesity (C2, BMI ≥ 35 kg/m2 , n = 14) and non-C2 (BMI < 35 kg/m2 , n = 18). Participants performed a bout of submaximal exercise followed by incremental stages of treadmill exercise to determine peak aerobic power (peak VO2 ). Peak VO2 and Ve/VCO2 were measured using Douglas bags while cardiac output (Qc) and stroke volume (SV) were measured by acetylene rebreathing. The C2 group were younger than the non-C2 group (67 ± 6 versus 73 ± 6 years; p = .009). Comorbid condition burden was similar between groups. Peak VO2 indexed to body mass was not significantly different between groups. Absolute peak VO2 was higher in the C2 group secondary to a larger peak Qc (14.3 versus 11.0 L/min; p = .012). SV reserve was also higher in the C2 group (72 versus 49%; p = .038). CONCLUSION: HFpEF patients with severe obesity had similar cardiorespiratory fitness compared to patients with lower BMI with similar comorbidity burden. Absolute VO2 was actually higher in the severely obese driven by larger Qc and SV reserve arguing against significant effects from obesity per se on aerobic performance. The presence of a larger "cardiac engine" may offer potential for fat-loss strategies to improve impairments in functional capacity in obese patients with HFpEF.

Elevated exercise blood pressure in middle-aged women is associated with altered left ventricular and vascular stiffness.

Women are at higher risk for developing heart failure with preserved ejection fraction (HFpEF). We examined the utility of peak exercise blood pressure (BP) in identifying preclinical features of HFpEF, namely vascular and cardiac stiffness in middle-aged women. We studied 47 healthy, nonobese middle-aged women (53 ± 5 yr). Oxygen uptake (V̇o2) and BP were assessed at rest and maximal treadmill exercise. Resting cardiac function and stiffness were assessed by echocardiography and invasive measurement (right heart catheterization) of left ventricular (LV) filling pressure under varying preloads. LV stiffness was calculated by curve fit of the diastolic portion of the pressure-volume curve. Aortic pulse-wave velocity was measured by arterial tonometry. Body fat was measured using dual-energy X-ray absorptiometry. Subjects in the highest exercise BP tertile had peak systolic BP of 201 ± 11 compared with 142 ± 19 mmHg in the lowest tertile (P < 0.001). Higher exercise BP was associated with increased age, percentage body fat, smaller LV size, slower LV relaxation, and increased LV and vascular stiffness. After adjustment, LV and arterial stiffness remained significantly associated with peak exercise BP. There was a trend toward increased body fat and slowed LV relaxation (both P < 0.07). In otherwise healthy middle-aged women, elevated exercise BP was independently associated with increased vascular stiffness and a smaller, stiffer LV, functional and structural risk factors characteristic for stages A and B HFpEF.NEW & NOTEWORTHY Women are at increased risk for heart failure with preserved ejection fraction (HFpEF) largely due to higher prevalence of arterial and cardiac stiffening. We were able to identify several subclinical markers of early (stages A and B) HFpEF pathophysiology largely on the basis of exercise blood pressure (BP) response in otherwise healthy middle-aged women. Exercise BP response may be an inexpensive screening tool to identify women at highest risk for developing future HFpEF.

Mechanisms of Chronotropic Incompetence in Heart Failure With Preserved Ejection Fraction.

BACKGROUND: Chronotropic incompetence is common in heart failure with preserved ejection fraction (HFpEF) and is associated with impaired aerobic capacity. We investigated the integrity of cardiac ß-receptor responsiveness, an important mechanism involved in exertional increases in HR, in HFpEF and control subjects. METHODS: Thirteen carefully screened patients with HFpEF and 13 senior controls underwent exercise testing and graded isoproterenol infusion to quantify cardiac ß-receptor-mediated HR responses. To limit autonomic neural influences on heart rate (HR) during isoproterenol, dexmedetomidine and glycopyrrolate were given. Isoproterenol doses were increased incrementally until HR increased by 30 beats per minute. Plasma levels of isoproterenol at each increment were measured by liquid chromatography with electrochemical detection and plotted against HR. RESULTS: Peak VO2 and HR (117±15 versus 156±15 beats per minute; P<0.001) were lower in HFpEF than senior controls. Cardiac ß-receptor sensitivity was lower in HFpEF compared to controls (0.156±0.133 versus 0.254±0.166 beats per minute/[isoproterenol ng/mL]; P<0.001). Seven of 13 HFpEF subjects had ß-receptor sensitivity similar to senior controls but still had lower peak HRs (122±14 versus 156±15 beats per minute; P<0.001). CONCLUSIONS: Contrary to our hypothesis, patients with HFpEF displayed impaired cardiac ß-receptor sensitivity compared with senior controls. In the 7 out of 13 patients with HFpEF with age-appropriate ß-receptor sensitivity, peak HR remained low, suggesting impaired sinus node ß-receptor function may not fully account for low exercise HR response. Rather in some patients with HFpEF, chronotropic incompetence might reflect premature cessation of exercise before maximal sinus node activation. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02524145.

Increased Myocardial Stiffness in Patients With High-Risk Left Ventricular Hypertrophy: The Hallmark of Stage-B Heart Failure With Preserved Ejection Fraction.

BACKGROUND: Individuals with left ventricular hypertrophy (LVH) and elevated cardiac biomarkers in middle age are at high risk for the development of heart failure with preserved ejection fraction (HFpEF). However, it is unknown what the pathophysiological underpinnings of this high-risk state may be. We tested the hypothesis that patients with LVH and elevated cardiac biomarkers would demonstrate elevated left ventricular (LV) myocardial stiffness in comparison with healthy controls as a key marker for future HFpEF. METHODS: Forty-six patients with LVH (LV septum >11 mm) and elevated cardiac biomarkers (N-terminal pro-B-type natriuretic peptide [>40 pg/mL] or troponin T [>0.6 pg/mL]) were recruited, along with 61 age- and sex-matched (by cohort) healthy controls. To define LV pressure-volume relationships, right heart catheterization and 3-dimensional echocardiography were performed while preload was manipulated using lower body negative pressure and rapid saline infusion. RESULTS: There were significant differences in body size, blood pressure, and baseline pulmonary capillary wedge pressure between groups (eg, pulmonary capillary wedge pressure: LVH, 13.4±2.7 versus control, 11.7±1.7 mm Hg, P<0.0001). The LV was less distensible in LVH than in controls (smaller volume for the same filling pressure). When preload was expressed as transmural filling pressure (pulmonary capillary wedge pressure - right atrial pressure), LV myocardial stiffness was nearly 30% greater in LVH than in controls (LVH stiffness constant, 0.053±0.027 versus controls, 0.042±0.020, P=0.028). CONCLUSIONS: LV myocardial stiffness in patients with LVH and elevated biomarkers (stage-B HFpEF) is greater than in age- and sex-matched controls and thus appears to represent a transitional state from a normal healthy heart to HFpEF. Although the LV myocardial stiffness of patients with LVH is greater than that of healthy controls at this early stage, further studies are required to clarify whether interventions such as exercise training to improve LV compliance may prevent the full manifestation of the HFpEF syndrome in these high-risk individuals. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifiers: NCT03476785 and NCT02039154.

The impact of 2 years of high-intensity exercise training on a model of integrated cardiovascular regulation.

KEY POINTS: Heart rate variability, a common and easily measured index of cardiovascular dynamics, is the output variable of complicated cardiovascular and respiratory control systems. Both neural and non-neural control mechanisms may contribute to changes in heart rate variability. We previously developed an innovative method using transfer function analysis to assess the effect of prolonged exercise training on integrated cardiovascular regulation. In the present study, we modified and applied this to investigate the effect of 2 years of high-intensity training on circulatory components to tease out the primary effects of training. Our method incorporated the dynamic Starling mechanism, dynamic arterial elastance and arterial-cardiac baroreflex function. The dynamic Starling mechanism gain and arterial-cardiac baroreflex gain were significantly increased in the exercise group. These parameters remained unchanged in the controls. Conversely, neither group experienced a change in dynamic arterial elastance. The integrated cardiovascular regulation gain in the exercise group was 1.34-fold larger than that in the control group after the intervention. In these previously sedentary, otherwise healthy, middle-aged adults, 2 years of high-intensity exercise training improved integrated cardiovascular regulation by enhancing the dynamic Starling mechanism and arterial-cardiac baroreflex sensitivity. ABSTRACT: Assessing the effects of exercise training on cardiovascular variability is challenging because of the complexity of multiple mechanisms. In a prospective, parallel-group, randomized controlled study, we examined the effect of 2 years of high-intensity exercise training on integrated cardiovascular function, which incorporates the dynamic Starling mechanism, dynamic arterial elastance and arterial-cardiac baroreflex function. Sixty-one healthy participants (48% male, aged 53 years, range 52-54 years) were randomized to either 2 years of exercise training (exercise group: n = 34) or control/yoga group (controls: n = 27). Before and after 2 years, subjects underwent a 6 min recording of beat-by-beat pulmonary artery diastolic pressure (PAD), stroke volume index (SV index), systolic blood pressure (sBP) and RR interval measurements with controlled respiration at 0.2 Hz. The dynamic Starling mechanism, dynamic arterial elastance and arterial-cardiac baroreflex function were calculated by transfer function gain between PAD and SV index; SV index and sBP; and sBP and RR interval, respectively. Fifty-three participants (controls: n = 25; exercise group: n = 28) completed the intervention. After 2 years, the dynamic Starling mechanism gain (Group × Time interaction: P = 0.008) and the arterial-cardiac baroreflex gain (P = 0.005) were significantly increased in the exercise group but remained unchanged in the controls. There was no change in dynamic arterial elastance in either of the two groups. The integrated cardiovascular function gain in the exercise group increased 1.34-fold, whereas there was no change in the controls (P = 0.02). In these previously sedentary, otherwise healthy middle-aged adults, a 2 year programme of high-intensity exercise training improved integrated cardiovascular regulation by enhancing the dynamic Starling mechanism and arterial-cardiac baroreflex sensitivity, without changing dynamic arterial elastance.

The effect of lifelong exercise dose on cardiovascular function during exercise.

An increased "dose" of endurance exercise training is associated with a greater maximal oxygen uptake (Vo2max), a larger left ventricular (LV) mass, and improved heart rate and blood pressure control. However, the effect of lifelong exercise dose on metabolic and hemodynamic response during exercise has not been previously examined. We performed a cross-sectional study on 101 (69 men) seniors (60 yr and older) focusing on lifelong exercise frequency as an index of exercise dose. These included 27 who had performed ≤ 2 exercise sessions/wk (sedentary), 25 who performed 2-3 sessions/wk (casual), 24 who performed 4-5 sessions/wk (committed) and 25 who performed ≥ 6 sessions/wk plus regular competitions (Masters athletes) over at least the last 25 yr. Oxygen uptake and hemodynamics [cardiac output, stroke volume (SV)] were collected at rest, two levels of steady-state submaximal exercise, and maximal exercise. Doppler ultrasound measures of LV diastolic filling were assessed at rest and during LV loading (saline infusion) to simulate increased LV filling. Body composition, total blood volume, and heart rate recovery after maximal exercise were also examined. Vo2max increased in a dose-dependent manner (P < 0.05). At maximal exercise, cardiac output and SV were largest in committed exercisers and Masters athletes (P < 0.05), while arteriovenous oxygen difference was greater in all trained groups (P < 0.05). At maximal exercise, effective arterial elastance, an index of ventricular-arterial coupling, was lower in committed exercisers and Masters athletes (P < 0.05). Doppler measures of LV filling were not enhanced at any condition, irrespective of lifelong exercise frequency. These data suggest that performing four or more weekly endurance exercise sessions over a lifetime results in significant gains in Vo2max, SV, and heart rate regulation during exercise; however, improved SV regulation during exercise is not coupled with favorable effects on LV filling, even when the heart is fully loaded.

Cardiovascular effects of 1 year of alagebrium and endurance exercise training in healthy older individuals.

BACKGROUND: Lifelong exercise training maintains a youthful compliance of the left ventricle (LV), whereas a year of exercise training started later in life fails to reverse LV stiffening, possibly because of accumulation of irreversible advanced glycation end products. Alagebrium breaks advanced glycation end product crosslinks and improves LV stiffness in aged animals. However, it is unclear whether a strategy of exercise combined with alagebrium would improve LV stiffness in sedentary older humans. METHODS AND RESULTS: Sixty-two healthy subjects were randomized into 4 groups: sedentary+placebo; sedentary+alagebrium (200 mg/d); exercise+placebo; and exercise+alagebrium. Subjects underwent right heart catheterization to define LV pressure-volume curves; secondary functional outcomes included cardiopulmonary exercise testing and arterial compliance. A total of 57 of 62 subjects (67 ± 6 years; 37 f/20 m) completed 1 year of intervention followed by repeat measurements. Pulmonary capillary wedge pressure and LV end-diastolic volume were measured at baseline, during decreased and increased cardiac filling. LV stiffness was assessed by the slope of LV pressure-volume curve. After intervention, LV mass and end-diastolic volume increased and exercise capacity improved (by ≈8%) only in the exercise groups. Neither LV mass nor exercise capacity was affected by alagebrium. Exercise training had little impact on LV stiffness (training × time effect, P=0.46), whereas alagebrium showed a modest improvement in LV stiffness compared with placebo (medication × time effect, P=0.04). CONCLUSIONS: Alagebrium had no effect on hemodynamics, LV geometry, or exercise capacity in healthy, previously sedentary seniors. However, it did show a modestly favorable effect on age-associated LV stiffening. CLINICAL TRIAL REGISTRATION- URL: http://www.clinicaltrials.gov. Unique identifier: NCT01014572.

The utility of capsule endoscopy and its role for diagnosing pathology in the gastrointestinal tract.

BACKGROUND: Capsule endoscopy (CE) is a new device that enables visualization of areas of the small bowel that were previously inaccessible through other noninvasive procedures. The purpose of this study is to evaluate this new diagnostic tool and its efficacy in finding occult GI tract pathology. METHODS: A single-institution retrospective review was completed on patients undergoing CE from January 2002 to September 2004. Data evaluated included indications for CE, results of previous studies, CE findings, and complications of the CE study. RESULTS: A total of 702 CE studies in 652 patients were performed during the study period. Suspicious GI bleeding presenting as anemia, guaiac positive stools, or history of gross bleeding were the most common reasons to perform CE (75.8%). Other indications included abdominal pain (11.5%), diarrhea (3.1%), or others (9.5%). In studies performed for GI bleeding (N = 532), a source was found in 49.3% of CE studies. Arteriovenous malformation (AVM) was the most common reported finding (43.9%), followed by ulcer (24.1%), colon or gastric pathology (14.1%), mass/tumor (9.1%), and stricture (6.9%). Patients with abdominal pain (n = 81) had findings 46.9% of the time including edema/ulcer (47.4%), stricture (10.5%), mass/tumor (26.3%), gastric pathology (10.5%), AVM (2.6%), or sprue (2.6%). Patients with diarrhea (n = 22) had findings 45.5% of the time including edema/ulcer (75%), mass/tumor (12.5%), or sprue (12.5%). A total of 66 patients underwent operative exploration after a CE study at this institution either because of the observed findings or for other reasons. There were 12 (1.7%) CE studies in which the capsule was retained and required surgical removal. Pathology at the retention site included benign strictures or adhesions (n = 9, 75%), Crohn's stricture (n = 1, 8.3%) carcinoid tumor (n = 1, 8.3%), and villous adenoma (n = 1, 8.3%). CONCLUSIONS: CE is an accurate study to locate abnormalities in the GI tract that may have either been missed by previous diagnostic studies or cannot be observed through other non-invasive means. When used for diagnostic challenges such as GI bleeding with no apparent source, CE can be helpful in guiding surgical decisions in patients and thus should be integrated as part of the diagnostic workup.

Survival analysis following sentinel lymph node biopsy: a validation trial demonstrating its accuracy in staging early breast cancer.

Few long-term follow-up studies prove sentinel lymph node biopsy (SLNB) effectively stages breast cancer without the further evaluation of a completion axillary dissection. Our prospective study addressed this issue, enrolling 345 women with clinically node-negative breast cancer who underwent SLNB from October 1997 through December 2000. The median age of the patients in the study was 56.7 years. Average primary tumor size was 1.42 cm. Ninety-three patients had a positive sentinel lymph node (27%); 70 (75.3%) of these patients underwent completion axillary dissection, while 23 patients (24.7%) declined further surgery. Most (91.3%) of the patients who declined further surgery had evidence of micrometastatic disease only. The median follow-up period for all patients was 60 months. No tumor recurrences in the axilla were reported in either sentinel node-negative or -positive patients. The local and systemic recurrence rates were 3.1% and 4% in node-negative patients and 2.2% and 4.3% in node-positive patients. Two patients (0.9%) in the node-negative group and 6 (6.5%) in the node-positive group died of their disease. Estimated 5-year disease-free survival rates were 96% for node-negative patients and 87% for node-positive patients (P = 0.02). The clinical false-negative rate of the SLNB in this study was 0%. This long-term validation trial proves the accuracy of the SLNB and its extremely low false-negative rate. The findings indicate that patients with a positive SLNB have significantly different survival rates than patients with a negative SLNB.

A prospective randomized trial demonstrating valved implantable ports have fewer complications and lower overall cost than nonvalved implantable ports.

BACKGROUND: The purpose of the current study was to evaluate whether a totally implanted valved subcutaneous port system would have fewer complications as compared to a standard nonvalved port. METHODS: Study subjects requiring port placement were randomized to receive a valved port (PASV; Boston Scientific, Natick, MA) or a nonvalved port (BardPort; Bard Accesss Systems, Salt Lake City, UT). Each port was placed with standard operative technique. Difficulty with blood return, excess time spent accessing the port, and required interventions were reported over the initial 180 days of port usage. RESULTS: Seventy-three patients were randomized to receive either a valved port (n = 37) or a nonvalved port (n = 36). No major complications were identified from port placement, and there were no differences in rates of infection between the 2 ports. A reported inability to withdraw blood was noted in the valved port group on 21 of 364 (5.8%) port accessions and in the nonvalved port group on 37 of 341 (11%) accessions (P = 0.02). Significantly more total time was spent ensuring adequate blood draw from nonvalved ports as opposed to valved ports (750 minutes vs. 1545 minutes, respectively) (P <0.03). CONCLUSIONS: This study revealed that the PASV valved port is associated with significantly fewer instances of poor blood return and less nursing access time, indicating that a port with a PASV valve may be superior to a nonvalved device.

Clinical benefits of leukocyte filtration during valve surgery.

BACKGROUND: The accumulation of activated leukocytes in the pulmonary circulation plays an important role in the pathogenesis of lung dysfunction associated with cardiopulmonary bypass (CPB). Patients undergoing valve surgery have prolonged CPB owing to the complexity of the surgery. The goal of this study is to determine if arterial leukocyte filters during CPB improve clinical outcomes after valve surgery. METHODS: A prospective analysis of all patients receiving only valve surgery with leukocyte arterial filters from June 1999 to June 2002 was compared with a case matched cohort during the same time period. Two hundred fifty patients were identified and compared with a cohort who did not have leukocyte filters used during CPB. The following study points were evaluated preoperatively and postoperatively: white blood cell count, platelet count, arterial blood gas, time to extubation, intensive care unit stay, and total length of hospital stay. RESULTS: There were 500 patients in the study. The following valve operations were performed: 92 mitral valve replacements, 168 aortic valve replacements, 152 mitral valve repairs, 80 combined valve repair/replacements, and 8 tricuspid valve repairs, all evenly divided between the two treatment limbs. Patients with leukocyte filters had the following findings compared with nonfilter patients: The time to extubation 10.3 versus 16.2 hours (P = 0.009), postoperative respiratory quotient 407 versus 320 (P = 0.02), total length of stay 5.4 versus 7.2 days (P = 0.04). CONCLUSIONS: The use of arterial leukocyte filters in patients undergoing valve surgery leads to earlier extubation, improved oxygenation, and a decreased length of stay. Leukocyte filters should be used during CPB for patients having valve surgery.

Preliminary outcome analysis in patients with breast cancer and a positive sentinel lymph node who declined axillary dissection.

BACKGROUND: This retrospective study was designed to provide a preliminary outcome analysis in patients with positive sentinel nodes who declined axillary dissection. METHODS: A review was conducted of patients who underwent lumpectomy and sentinel lymph node excision for invasive disease between January 1998 and July 2000. Those who were found to have sentinel lymph node metastasis without completion axillary dissection were selected for evaluation. Follow-up included physical examination and mammography. RESULTS: Thirty-one patients were identified who met inclusion criteria. Primary invasive cell types included infiltrating ductal carcinoma, infiltrating lobular carcinoma, and mixed cellularity. Most primary tumors were T1. Nodal metastases were identified by hematoxylin and eosin stain and immunohistochemistry. Twenty-seven of the metastases were microscopic (<2 mm), and the remaining four were macroscopic. All patients received adjuvant systemic therapy. With a mean follow-up of 30 months, there have been no patients with axillary recurrence on physical examination or mammographic evaluation. CONCLUSIONS: We have presented patients with sentinel lymph nodes involved by cancer who did not undergo further axillary resection and remain free of disease at least 1 year later. This preliminary analysis supports the inclusion of patients with subclinical axillary disease in trials that randomize to observation alone.

Sentinel lymph node biopsy followed by delayed mastectomy and reconstruction.

BACKGROUND: The role of sentinel lymph node (SLN) biopsy with total mastectomy is evolving. In patients who desire mastectomy with immediate reconstruction, the final pathologic results of the SLN may create unique problems. Specifically, if the SLN is found to be positive on final pathology, the reconstructed patient would generally require a potentially difficult re-operation on the remaining axillary nodes. The purpose of this study was to review the results of patients who underwent an initial SNL biopsy followed by a planned mastectomy and reconstruction. METHODS: A chart review of patients who underwent staged SLN biopsy with subsequent definitive procedure between 1997 and 2001 was conducted. These were evaluated with regard to type of tumor, status of sentinel node, and design of subsequent operation. RESULTS: There were 40 patients who underwent an initial SLN biopsy followed by a staged mastectomy with reconstruction. Tumors included high-grade carcinoma in situ (n = 4), infiltrating ductal carcinoma (n = 28), invasive lobular carcinoma (n = 4), mucinous carcinoma (n = 1), adenoid cystic carcinoma (n = 1), and mixed ductal and lobular carcinoma (n = 2). Tissue biopsy was obtained by either open (n = 9) or needle (n = 31) technique. Twenty-five patients had a negative SLN biopsy and a delayed total mastectomy with immediate reconstruction. Positive SLNs were identified in 15 patients (37%). Eight patients had macroscopic nodal metastases and underwent a delayed modified radical mastectomy and immediate reconstruction. Seven patients had microscopic nodal metastases and 3 declined further axillary dissection. They proceeded with total mastectomy and immediate reconstruction. CONCLUSIONS: These data suggest that a substantial proportion of patients treated with SLN biopsy, simple mastectomy, and reconstruction will have positive sentinel lymph nodes. Thus, the ideal approach for patients who wish to have reconstruction should involve an initial SLN biopsy as a separate procedure. If the SLN is benign, the patient may undergo a total mastectomy with immediate reconstruction. However, a patient with a positive SLN may proceed to a modified radical mastectomy with immediate reconstruction. This treatment algorithm eliminates a potentially difficult reoperation on the axilla following reconstruction.

Predictors for nonsentinel node involvement in breast cancer patients with micrometastases in the sentinel lymph node.

Sentinel lymph node (SLN) biopsy in breast cancer allows for a more thorough pathologic assessment with serial sectioning and cytokeratin staining. This has resulted in increased detection of micrometastatic disease (tumor size < 2 mm) in the SLN. Unfortunately, the value of completion axillary dissection after finding micrometastatic disease in the SLN remains poorly defined. Over a 2-year period, a prospective database of 305 patients who underwent SLN biopsy for breast cancer at Baylor University Medical Center was reviewed. Eighty-four (27.5%) of the patients had evidence of metastatic disease in the SLN. Twenty-four of the 41 patients identified as having micrometastatic disease in the SLN underwent completion axillary lymph node dissection. In these patients, all nonsentinel nodes were further studied by serial sectioning and immunohistochemistry. The median age of these 24 patients was 52 years (range, 34-83). Their primary tumor stages were T1a and T1b (n = 5), T1c (n = 15), and T2 (n = 4). A total of 328 nonsentinel lymph nodes were examined, including 225 from patients with infiltrating ductal carcinoma (n = 17) and 103 from patients with infiltrating lobular carcinoma (n = 7). In the patients with infiltrating ductal carcinoma, no additional nodal metastases were identified, while in those with infiltrating lobular carcinoma, additional nodal disease was found in 5 lymph nodes (2 of 12 patients, 17%). Primary tumor characteristics were not predictive of additional nodal disease. These data suggest that patients with micro-metastasis in the SLN from infiltrating lobular carcinoma have a significant risk of harboring additional nodal disease and should undergo completion axillary dissection. However, those with micrometastatic disease from infiltrating ductal carcinoma have a very low incidence of additional metastasis and may not need completion axillary dissection.

A randomized trial of valved vs nonvalved implantable ports for vascular access.

BACKGROUND: Vascular access devices placed into the central venous system are used routinely in the medical management of many patients. Catheter tip occlusion is a common complication of open-ended catheters, causing difficulty with blood withdrawal and infusion. This study evaluated whether a valved subcutaneous port system would have fewer associated complications than a standard nonvalved port. METHODS: Study subjects requiring port placement were randomized to receive a PASV (valved) port or a nonvalved BardPort. Standard technique was used to place both types of ports. Patients were monitored for 180 days after implantation, and data on major complications were collected. Difficulty with blood return and excess time spent accessing the port were studied as indicators of catheter tip occlusion. This study is an interim analysis of an ongoing prospective study, with an anticipated accrual of 100 patients. RESULTS: Fifty-four patients were randomized to receive either the PASV port (n = 27) or a BardPort (n = 27). All patients required venous access for treatment of malignancy. No major complications were identified from port placement. No patient had major sepsis due to infected catheters. Overall complications included catheter leakage in 1 patient (3.7%, BardPort) and venous thrombosis in 1 patient in each group (3.7% per group). Difficulty in blood draw was noted in the PASV group on 16 of 273 (5.9%) port accessions and in the BardPort group on 30 of 266 (11.3%) accessions (P = 0.04). Thrombolytic agents were required in 14 (5.1%) port accessions in the PASV group and 21 (7.9%) port accessions in the BardPort group (P = 0.25). Significantly more total time was spent ensuring adequate blood draw from BardPorts as opposed to PASV ports (870 vs 435 minutes, respectively) (P = 0.01). CONCLUSION: This initial analysis reveals that the valved PASV port system is associated with significantly fewer instances of poor blood return and thus decreases the time required for nurses to obtain blood return before infusion.