Comparison of Blood Volume Profiles in Heart Failure With Preserved and Reduced Ejection Fractions: Sex Makes a Difference.

BACKGROUND: Blood volume (BV) profiles vary markedly in patients with heart failure (HF), but how HF phenotypes and patient sex impact volume profiles remain to be explored. The aim of the study was to differentiate BV, plasma volume, and red blood cell mass profiles by phenotypes of preserved and reduced left ventricular ejection fractions and assess the impact of patient sex on profile heterogeneity. METHODS: Retrospective analysis of clinical and BV data was undertaken in patients with chronic New York Heart Association II-III heart failure. BV was quantitated using the nuclear medicine indicator-dilution methodology. RESULTS: A total of 530 BV analyses (360 HF with reduced ejection fraction and 170 HF with preserved ejection fraction) were identified in 395 unique patients. Absolute BV was greater in HF with reduced ejection fraction (6.7±1.8 versus 5.9±1.6 liters: P<0.001); however, large variability in frequency distribution of volume profiles was observed in both phenotypes (-22% deficit to +109% excess relative to normal volumes). HF with reduced ejection fraction was characterized by a higher prevalence of BV expansion ≥+25% of normal (39% versus 26%; P=0.003), and HF with preserved ejection fraction was characterized a by more frequent normal BV (42% versus 24%; P<0.001). Male sex in both phenotypes was associated with a larger absolute BV (7.0±1.6 versus 5.1±1.3 liters; P<0.001) and higher frequency of large BV and plasma volume expansions above normal (both P<0.001), while females in both phenotypes demonstrated a higher prevalence of normal BV and plasma volume (both P<0.001). CONCLUSIONS: Findings support significant differences in BV, plasma volume, and red blood cell mass profile distributions between heart failure phenotypes, driven in large part by sex-specific factors. This underscores the importance of identifying and distinguishing individual patient volume profiles to help guide volume management strategies.

Differences in red blood cell mass profiles impact intravascular volume and outcome risk in chronic heart failure.

AIMS: To identify different red blood cell mass (RBCM) profiles, separate from haemoglobin concentrations, and their impact on blood volume expansion and clinical outcomes in chronic heart failure. METHODS AND RESULTS: RBCM was measured at hospital discharge using standardized nuclear medicine indicator-dilution methodology in patients following diuretic treatment for clinical congestion. Individual RBCM phenotypes were prospectively identified and analysed for heart failure-related mortality or first rehospitalization over 1 year. Of 132 patients, 42 (32%) demonstrated normal RBCM, 36 (27%) RBCM deficit (true anaemia), and 54 (41%) RBCM excess (erythrocythemia). Dilutional 'anaemia' defined by haemoglobin <12 g/dL with normal or an excess in RBCM with plasma volume expansion was identified in 37 (28%) patients. There were 61 composite outcome events, which included 38 deaths (29% of cohort) occurring over the 1 year follow-up period [14/36 (39%) in RBCM deficit, 12/42 (29%) in normal RBCM, and 12/54 (22%) in RBCM excess subgroups]. By Kaplan-Meier and multivariate analyses, RBCM excess was independently associated with the best event-free survival while RBCM deficit (true anaemia) the poorest outcomes; both compared with normal RBCM (P < 0.001). Dilutional 'anaemia' demonstrated a lower risk compared with true anaemia (P = 0.03). CONCLUSIONS: Markedly different RBCM profiles are identifiable among comparably compensated heart failure patients, and this variability carries significant implications for post-hospital outcomes. Novel to this analysis and in contrast to RBCM deficit is the independent association of RBCM excess with better event-free survival compared with normal RBCM. The distinction of RBCM profiles to guide risk stratification and individualized patient management strategies warrants further study.

Blood volume and chronic kidney disease in heart failure - Can volume expansion help balance the Cardio-Renal Axis for better clinical outcomes?

Intravascular volume is largely regulated by the kidneys but how differences in intravascular volume profiles interact with chronic kidney disease (CKD) to influence outcomes in chronic heart failure (HF) has not been explored. Our hypothesis was that a greater degree of volume expansion (VE) would moderate the impact of CKD on HF-related clinical outcomes. Quantitative blood volume (BV) data were available in 137 patients at the time of hospital discharge using a nuclear medicine radiolabeled albumin indicator-dilution technique. The study patients were stratified by the cohort median glomerular filtration rate (GFR, 44 ml/min/1.73 m2 ). An a priori cut-point of ≥+25% above normal BV was then used to further stratify the two GFR subgroups and prospectively analyzed for 1-year HF-related mortality or 1st re-hospitalization. Persistent BV expansions ≥+25% were present in 51% of the cohort. In the subgroup with GFR above the median (N = 68) greater or lesser BV expansion from +25% did not differentiate outcomes. However, in the subgroup with GFR below the median (N = 69), BV expansion-stratified risk (log-rank p = 0.022) with <+25% VE associated with poorer outcomes, while VE ≥ + 25% was associated with lower risk and comparable to GFR above the median. In patients with chronic HF, significant intravascular VE and CKD are common co-existing conditions. The presence of larger VE, however, appears to be a factor mitigating the impact of declining renal function on clinical outcomes, and as an element of volume pathophysiology warrants further study.

Blood volume expansion, normovolemia, and clinical outcomes in chronic human heart failure: more is better.

Expansion in blood volume (BV) is a well-recognized response to arterial underfilling secondary to impaired cardiac output in heart failure (HF). However, the effectiveness of this response in terms of outcomes remains inadequately understood. Prospective analysis was undertaken in 110 patients with HF hospitalized and treated for fluid overload. BVs were measured in a compensated state at the hospital discharge using the indicator-dilution methodology. Data were analyzed for composite 1-year HF-related mortality/first rehospitalization. Despite uniform standard of care, marked heterogeneity in BVs was identified across the cohort. The cohort was stratified by BV expansion greater than or equal to +25% above normal (51% of cohort), mild-moderate expansion (22%), and normal BV (27%). Kaplan-Meier (K-M) survival estimates and regression analyses revealed BV expansion (greater than or equal to +25%) to be associated with better event-free survival relative to normal BV (P = 0.038). Increased red blood cell mass (RBCm; RBC polycythemia) was identified in 43% of the overall cohort and 70% in BV expansion greater than or equal to +25%. K-M analysis demonstrated polycythemia to be associated with better outcomes compared with normal RBCm (P < 0.002). Persistent BV expansion to include RBC polycythemia is common and, importantly, associated with better clinical outcomes compared with normal total BV or normal RBCm in patients with chronic HF. However, compensatory BV expansion is not a uniform physiological response to the insult of HF with marked variability in BV profiles despite uniform standard of care diuretic therapy. Therefore, recognizing the variability in volume regulation pathophysiology has implications not only for impact on clinical outcomes and risk stratification but also potential for informing individualized volume management strategies.NEW & NOTEWORTHY The novel findings of this study demonstrate that intravascular volume profiles among the patients with chronic heart failure (HF) vary substantially even with similar clinical compensation. Importantly, a profile of blood volume (BV) expansion (compared with a normal BV) is associated with lower HF mortality/morbidity. Furthermore, RBC polycythemia is common and independently associated with improved outcomes. These observations support BV expansion with RBC polycythemia as a compensatory mechanism in chronic HF.

Diuresis-Related Weight Loss Reflects Interstitial Compartment Decongestion with Minimal Impact on Intravascular Volume Expansion or Outcomes in Post-Acute Heart Failure: Metrics of Decongestion and Volume Status.

BACKGROUND: Findings from heart failure (HF) studies linking diuresis-related weight loss to clinical decongestion and outcomes are mixed. Differential responses of interstitial and intravascular volume compartments to diuretic therapy and heterogeneity in volume profiles may confound the clinical interpretation of weight loss in patients with HF. METHODS AND RESULTS: Data were prospectively collected in hospitalized patients requiring diuresis. Plasma volume (PV) was measured using I-131-labelled albumin indicator-dilution methodology. The cohort was stratified by tertiles of weight loss and analyzed for interstitial fluid loss relative to changes in PV and HF-related morality or first rehospitalization. Among 92 patients, the admission PV was expanded +42% (4.7 ± 1.2 L) above normal with significant variability (14% normal PV, 18% mild-moderate expansion, and 68% with large PV expansion [>+25% above normal]). With diuresis there were proportional decreases in interstitial volume (-6.5 ± 4.4%) and PV (-7.5 ± 11%); however, absolute decreases in the PV (-254 mL, interquartile range -11 to -583 mL) were less than 10% of interstitial volume loss (-5040 mL, interquartile range -2800 to -7989 mL); greater interstitial fluid loss did not translate into better outcomes (log-rank P = .430). CONCLUSIONS: Diuresis-related decreases in weight reflect fluid loss from the interstitial compartment with only minor changes in the PV and without an impact on outcomes. Further, the degree of PV expansion at hospital admission does not drive the magnitude of the diuresis response, even with a wide spectrum of body weights; interstitial fluid overload is preferentially targeted and PV relatively preserved. Therefore, greater interstitial fluid loss reflects clinical decongestion, but not better outcomes, and a limited association with intravascular volume profiles potentially confounding weight loss as a prognostic metric in HF.

Myocardial Energetics in Heart Failure With Preserved Ejection Fraction.

BACKGROUND: The role of coronary microvascular disease and its impact on functional and energetic reserve in heart failure with preserved ejection fraction (HFpEF) remains unclear. We hypothesized that in response to submaximal pharmacologic stress (dobutamine), patients with HFpEF have impairment in left ventricular (LV) myocardial mechanical (external work [EW]), energetic (myocardial O2 consumption [MVO2]), and myocardial blood flow (MBF) reserve. We further assessed whether coupling of MBF to EW is impaired in HFpEF and associated with compensatory increases or pathological decreases in myocardial O2 extraction. Lastly, we assessed whether coupling of MVO2 to EW (mechanical efficiency) was impaired in HFpEF. METHODS AND RESULTS: In prospectively enrolled patients with HFpEF (n=19) and age/sex-matched healthy controls (n=19), we performed 11C-acetate positron emission tomography assessing MVO2 and MBF at rest and during dobutamine infusion. EW was calculated as stroke volume (echo)×end-systolic pressure×heart rate. At rest, compared with controls, patients with HFpEF had higher LV EW, MVO2, and MBF. With dobutamine, LV EW, MVO2, and MBF increased in both HFpEF and controls; however, the magnitude of increases was significantly smaller in HFpEF. In both groups, MBF increased in relation to EW, but in HFpEF, the slope of the relationship was significantly smaller than in controls. Myocardial O2 extraction was increased in HFpEF. Mechanical efficiency was similar in HFpEF and controls. In a post hoc analysis, HFpEF patients with LV hypertrophy (n=10) had significant reductions in LV mechanical efficiency relative to controls. CONCLUSIONS: In HFpEF during submaximal dobutamine stress, there is myocardial mechanical-, energetic- and flow-reserve dysfunction with impaired coupling of blood flow to demand and slight increases in myocardial O2 extraction. These findings provide evidence that coronary microvascular dysfunction is present in HFpEF, limits O2 supply relative to demand, and is associated with reserve dysfunction.

Analysis of Brain SPECT Images Coregistered with MRI in Patients with Epilepsy: Comparison of Three Methods.

BACKGROUND AND PURPOSE: SISCOM and STATISCOM were clinically proved to be effective for ictal/inter-ictal single-photon emission computed tomography (SPECT) analysis coregistered with magnetic resonance imaging (MRI) for seizure localization. Recently, a software package also became available for this analysis. This study aimed to investigate and compare the performance of these analysis methods for seizure localization. METHODS: A total of 378 patients who underwent 99m Tc-ethyl cysteinate dimer (ECD) SPECT scans were retrospectively reviewed and 28 remained after applying exclusion criteria. Their SPECT and MRI images were analyzed with SISCOM (with z-score of 1.5 and 2), STATISCOM, and MIMneuro, resulting in a total of 112 image data sets. Two experienced radiologists participated in the blind review process using a custom tool and they can mark up to two hyper- and/or hypoperfusion regions. Their review results were analyzed using the Jackknife Free Response Receiver-Operating Characteristics (JAFROC) test and the JAFROC figure-of-merit (FoM) was reported for each method. The interobserver agreement was also assessed using Cohen's kappa test. RESULTS: Based on the readers' two choices, averaged FoM was 85.7%, 83.9%, 66.1%, and 51.8% for STATISCOM, MIMneuro, SISCOM (z-score = 2), and SISCOM (z-score = 1.5), respectively. The average confidence rating was 2.5, 2.3, 1.6, and 1.1 for STATISCOM, MIMneuro, SISCOM (z-score = 2), and SISCOM (z-score = 1.5), respectively. For interobserver agreement, kappa was .742 for STATISCOM, .816 for MIMneuro, .517 for SISCOM (z-score = 2), and .441 for SISCOM (z-score = 1.5; all P < .001). CONCLUSION: Our study demonstrated that STATISCOM showed the best performance for seizure localization, which was closely followed by MIMneuro. In addition, MIMneuro was not inferior to SISCOM with either z-score.

Intravascular Volume Profiles in Patients With Class I and II Systolic Heart Failure: Heterogeneity and Volume Overload Are Common Even in Mild Heart Failure.

BACKGROUND: Although volume overload is a commonly described clinical feature of advanced heart failure (HF), less is known regarding volume profiles of patients with less severe class I and II HF. METHODS: Intravascular volume was quantitated by radiolabeled-albumin indicator-dilution technique in clinic outpatients. RESULTS: Forty-six patients (age 61 ± 13years, left ventricular ejection fraction 30 ± 8%) were prospectively evaluated with 28 undergoing repeat evaluations at 1 year. There was no difference in averaged total blood volume (TBV) at baseline between class I (N = 26) and II (N = 20) patients (5.6 ± 1.6vs 6.0 ± 1.3 L, P = .368) and at 1-year of follow-up. However, there was marked heterogeneity in plasma volume (-13% to +69% of normal) and red cell mass (RBCM -31% to +50%) profiles with TBV expansion identified in 46% of the cohort, whereas only 48% had a normal TBV. RBCM deficit (true anemia) was common (39%), but a low hemoglobin concentration was accurate in identifying anemia in only 11% of the cohort. RBCM excess (polycythemia) also was identified in 20% of the cohort. CONCLUSIONS: Marked heterogeneity in plasma volume and RBCM volume profiles is present even in mild HF, and identifying volume overload, which was common in early HF, has the potential to help guide therapy in the reduction of HF progression. Intravascular volume as a modifiable risk factor in early HF warrants further study.

11C-Choline PET/CT for Detection and Localization of Parathyroid Adenomas.

OBJECTIVE: The purpose of this study is to determine the efficacy of 11C-choline PET/CT for the detection of parathyroid adenomas by retrospectively reviewing a large patient population. MATERIALS AND METHODS: In this single-institution retrospective study, 7088 11C-choline PET/CT scans performed of 2933 men with prostate cancer from January 2005 through February 2016 were evaluated. Patients with suspected parathyroid adenomas were identified through a review of the electronic medical record and relevant imaging. Patient demographics, laboratory results, and lesion characteristics were noted. Pathologically proven parathyroid adenomas and lesions in patients with imaging or laboratory findings consistent with the diagnosis were considered positive. RESULTS: Thirteen men (mean [± SD] age, 72 ± 7 years) with pathologically or laboratory-proven parathyroid adenomas were identified. All had abnormally elevated serum calcium and parathyroid hormone levels. All adenomas were tracer avid on 11C-choline PET/CT (maximum standardized uptake value, 5.6 ± 3.0), with activity averaging 4.2 times that of the blood pool and 2.1 times that of the adjacent thyroid. One case of an ectopic adenoma was identified. Of the six pathologically confirmed cases, none displayed high-grade features such as capsular, vascular, or adjacent tissue invasion. Three additional patients with possible parathyroid adenomas at 11C-choline PET/CT were ultimately found to have thyroid lesions on the basis of tissue diagnosis; however, none of these patients had abnormal calcium or parathyroid hormone levels. CONCLUSION: In our patient population, 11C-choline PET/CT identified parathyroid adenomas with high specificity. Prospective investigation is warranted to validate this result and delineate the utility of 11C-choline PET/CT relative to other modalities.

Volume Overload Profiles in Patients With Preserved and Reduced Ejection Fraction Chronic Heart Failure: Are There Differences? A Pilot Study.

OBJECTIVES: This study aimed to characterize volume profiles and their differences in heart failure (HF) patients with preserved (HFpEF) and reduced (HFrEF) ventricular systolic function. BACKGROUND: The extent and distribution of volume overload and the associated implications for volume management have not been studied in decompensated HFpEF compared with HFrEF. METHODS: Total blood volume (TBV) was quantitated using a standardized computer-based radiolabeled albumin dilution technique. RESULTS: Twenty HFpEF and 35 HFrEF patients were evaluated at hospital admission. TBV was expanded by 27 ± 21% (range -5.2% to 77%; p = 0.002) and 37 ± 25% (0% to 107%; p < 0.001), respectively, above normal volumes. Red cell mass (RBCM) was expanded in HFrEF (24 ± 31%; p = 0.004) but within normal limits in HFpEF (8 ± 34%; p = 0.660) with, however, large variability in both groups. RBCM excess was more prominent in HFrEF (63% vs. 45%) than the RBCM deficit in HFpEF (35% vs.14%). With diuresis, TBV decreased to 25 ± 20% (p = 0.029) in HFrEF but was not changed in HFpEF (18 ± 20% [p = 0.173]). Body weight declined 6.6 ± 4.4 kg in HFrEF and 10.5 ± 8.3 kg (p = 0.026) in HFpEF. Interstitial fluid losses accounted for 85 ± 13% (HFrEF) and 93 ± 6% (HFpEF) (p = 0.012) of total volume removed. CONCLUSIONS: TBV profiles differ between HFpEF and HFrEF patients with DCHF. Quantitated volume analysis revealed both significant RBCM (polycythemia) and plasma volume excess in HFrEF, whereas a higher RBCM deficit (true anemia) was demonstrated in HFpEF. Diuresis produced only a modest reduction in intravascular volumes with persistent hypervolemia in both groups at discharge, but overall more total body fluid was lost in HFpEF. These profile differences have implications for individualizing volume management.

A Multimodal Imaging Protocol, (123)I/(99)Tc-Sestamibi, SPECT, and SPECT/CT, in Primary Hyperparathyroidism Adds Limited Benefit for Preoperative Localization.

INTRODUCTION: Focused parathyroidectomy in primary hyperparathyroidism (1°HPT) is possible with accurate preoperative localization and intraoperative PTH monitoring (IOPTH). The added benefit of multimodal imaging techniques for operative success is unknown. METHOD: Patients with 1°HPT, who underwent parathyroidectomy in 2012-2014 at a single institution, were retrospectively reviewed. Only the patients who underwent the standardized multimodal imaging workup consisting of (123)I/(99)Tc-sestamibi subtraction scintigraphy, SPECT, and SPECT/CT were assessed. RESULTS: Of 360 patients who were identified, a curative operation was performed in 96%, using pre-operative imaging and IOPTH. Imaging analysis showed that (123)I/(99)Tc-sestamibi had a sensitivity of 86% (95% CI 82-90%), positive predictive value (PPV) 93%, and accuracy 81%, based on correct lateralization. SPECT had a sensitivity of 77% (95% CI 72-82%), PPV 92% and accuracy 72%. SPECT/CT had a sensitivity of 75% (95% CI 70-80%), PPV of 94%, and accuracy 71%. There were 3 of 45 (7%) patients with negative sestamibi imaging that had an accurate SPECT and SPECT/CT. Of 312 patients (87%) with positive uptake on sestamibi (93% true positive, 7% false positive), concordant findings were present in 86% SPECT and 84% SPECT/CT. In cases where imaging modalities were discordant, but at least one method was true-positive, (123)I/(99)Tc-sestamibi was significantly better than both SPECT and SPECT/CT (p < 0.001). The inclusion of SPECT and SPECT/CT in 1°HPT imaging protocol increases patient cost up to 2.4-fold. CONCLUSION: (123)I/(99)Tc-sestamibi subtraction imaging is highly sensitive for preoperative localization in 1°HPT. SPECT and SPECT/CT are commonly concordant with (123)I/(99)Tc-sestamibi and rarely increase the sensitivity. Routine inclusion of multimodality imaging technique adds minimal clinical benefit but increases cost to patient in high-volume setting.

Peripheral Venous Hemoglobin and Red Blood Cell Mass Mismatch in Volume Overload Systolic Heart Failure: Implications for Patient Management.

Peripheral venous hemoglobin (Hb) measurements are considered to accurately reflect circulating red blood cell mass (RBCM). In volume overload decompensated chronic heart failure (DCHF), reliance on Hb values may be misleading. Using quantitative radiolabel blood volume analysis (BVA), we evaluated the relation of RBCM to volume overload and reliability of Hb measurements to reflect RBC status in patients hospitalized for DCHF. Of 32 patients evaluated (LVEF <50 %), 19 met WHO Hb criteria for anemia. By BVA, however, only 4/19 had true anemia (low Hb and low RBCM) while 15/19 demonstrated plasma volume expansion dilution-related "anemia" (6 low Hb/normal RBCM, 9 low Hb/excess RBCM). The remaining 13/32 had normal range Hb (12 with excess RBCM). Overall, 66 % of cohort demonstrated RBCM excess. RBC profiles are highly variable in DCHF, and peripheral Hb values are often misleading in identifying RBC status. These findings have implications for volume management.

Understanding the heterogeneity in volume overload and fluid distribution in decompensated heart failure is key to optimal volume management: role for blood volume quantitation.

OBJECTIVES: This study sought to quantitate total blood volume (TBV) in patients hospitalized for decompensated chronic heart failure (DCHF) and to determine the extent of volume overload, and the magnitude and distribution of blood volume and body water changes following diuretic therapy. BACKGROUND: The accurate assessment and management of volume overload in patients with DCHF remains problematic. METHODS: TBV was measured by a radiolabeled-albumin dilution technique with intravascular volume, pre-to-post-diuretic therapy, evaluated at hospital admission and at discharge. Change in body weight in relation to quantitated TBV was used to determine interstitial volume contribution to total fluid loss. RESULTS: Twenty-six patients were prospectively evaluated. Two patients had normal TBV at admission. Twenty-four patients were hypervolemic with TBV (7.4 ± 1.6 liters) increased by +39 ± 22% (range, +9.5% to +107%) above the expected normal volume. With diuresis, TBV decreased marginally (+30 ± 16%). Body weight declined by 6.9 ± 5.2 kg, and fluid intake/fluid output was a net negative 8.4 ± 5.2 liters. Interstitial compartment fluid loss was calculated at 6.2 ± 4.0 liters, accounting for 85 ± 15% of the total fluid reduction. CONCLUSIONS: TBV analysis demonstrated a wide range in the extent of intravascular overload. Dismissal measurements revealed marginally reduced intravascular volume post-diuretic therapy despite large reductions in body weight. Mobilization of interstitial fluid to the intravascular compartment with diuresis accounted for this disparity. Intravascular volume, however, remained increased at dismissal. The extent, composition, and distribution of volume overload are highly variable in DCHF, and this variability needs to be taken into account in the approach to individualized therapy. TBV quantitation, particularly serial measurements, can facilitate informed volume management with respect to a goal of treating to euvolemia.

Statistical SPECT processing in MRI-negative epilepsy surgery.

OBJECTIVE: To evaluate the benefit of statistical SPECT processing over traditional subtraction methods, we compared ictal-interictal SPECT analyzed by statistical parametric mapping (SPM) (ISAS), statistical ictal SPECT coregistered to MRI (STATISCOM), and subtraction ictal-interictal SPECT coregistered with MRI (SISCOM) in patients with MRI-negative focal temporal lobe epilepsy (nTLE) and extratemporal lobe epilepsy (nETLE). METHODS: We retrospectively identified 49 consecutive cases of drug-resistant focal epilepsy that had a negative preoperative MRI and underwent interictal and ictal SPECT prior to resective epilepsy surgery. Interictal and ictal SPECT scans were analyzed using SISCOM, ISAS, and STATISCOM to create hyperperfusion and hypoperfusion maps for each patient. Reviewers blinded to clinical data and the SPECT analysis method marked the site of probable seizure origin and indicated their confidence in the localization. RESULTS: In nTLE and nETLE, the hyperperfusions detected by STATISCOM (71% nTLE, 57% nETLE) and ISAS (67% nTLE, 53% nETLE) were more often colocalized with surgery resection site compared to SISCOM (38% nTLE, 36% nETLE). In nTLE, localization of the hyperperfusion to the region of surgery was associated with an excellent outcome for STATISCOM (p = 0.005) and ISAS (p = 0.027), but not in SISCOM (p = 0.071). This association was not present in nETLE for any method. CONCLUSION: In an unselected group of patients with normal MRI and focal epilepsy, SPM-based methods of SPECT processing showed better localization of SPECT hyperperfusion to surgical resection site and higher interobserver agreement compared to SISCOM. These results show the benefit of statistical SPECT processing methods and further highlight the challenge of nETLE.

The role of autonomic testing in the differentiation of Parkinson's disease from multiple system atrophy.

Differentiation of idiopathic Parkinson's disease (PD) from multiple system atrophy (MSA) can be difficult. Methods devised to help distinguish the two disorders include standardized autonomic testing and cardiac imaging with iodine-123 meta-iodobenzylguanidine myocardial scintigraphy. MSA patients had more severe adrenergic and overall autonomic dysfunction when compared to control and PD patients. Area of anhidrosis on thermoregulatory sweat test was greater in MSA (67.4±12.42, p<0.001) versus PD patients (area of anhidrosis, 1.7±2.96). Postganglionic cardiac sympathetic innervation (iodine-123 meta-iodobenzylguanidine) expressed as heart to mediastinal ratio was significantly lower in Parkinson's disease patients (1.4±0.40, p=0.025) compared to controls (2.0±0.29), but not in multiple system atrophy (2.0±0.76). These findings indicate that autonomic dysfunction is generalized and predominantly preganglionic in multiple system atrophy, and postganglionic in Parkinson's disease. In our hands the thermoregulatory sweat test provides the best distinction between MSA and PD. However further confirmatory studies using larger patient numbers are required. Currently a combination of clinical judgment and autonomic testing is recommended to help differentiate MSA and PD.

Measurement of left and right ventricular volumes with tomographic equilibrium radionuclide angiocardiography and cardiac MRI.

OBJECTIVE: We previously developed an operator-interactive method for the measurement of left ventricular (LV) and right ventricular (RV) ejection fraction (EF) and end-systolic volume (ESV) and end-diastolic volume (EDV) using single-photon emission tomographic equilibrium radionuclide angiocardiography (SPECT ERNA). We aimed to compare our SPECT ERNA method with cardiac MRI (CMRI) for the determination of ventricular measures. METHODS: Paired measurements of LV and RV EFs and ESV and EDV were carried out by SPECT ERNA and CMRI in a group of patients who had myocardial infarction due to left anterior descending coronary artery thrombosis. RESULTS: SPECT ERNA and CMRI provided similar estimations of the mean (SD) LV ESV [61 (23) vs. 61 (32) ml; P=0.99] and LV EDV [134 (29) vs. 141 (44) ml; P=0.28]. The mean (SD) LV EF by SPECT ERNA was slightly but significantly smaller than that by CMRI [0.55 (0.10) vs. 0.58 (0.11) ml; P=0.03]. SPECT ERNA, compared with CMRI, produced similar mean (SD) values of RV ESV [62 (17) vs. 67 (17) ml; P=0.10] and RV EDV [153 (28) vs. 149 (29) ml; P=0.51] and somewhat larger mean (SD) RV EF [0.60 (0.06) vs. 0.55 (0.06) ml; P<0.001]. Excellent correlations were found between SPECT ERNA and CMRI for combined LV ESV and EDV (R=0.85, P<0.001) and combined RV ESV and EDV (R=0.85, P<0.001). CONCLUSION: This study further validates SPECT ERNA as a method to measure LV and RV EF, ESV, and EDV.

Statistical parametric mapping demonstrates asymmetric uptake with Tc-99m ECD and Tc-99m HMPAO SPECT in normal brain.

Tc-99m ethyl cysteinate diethylester (ECD) and Tc-99m hexamethyl propylene amine oxime (HMPAO) are commonly used for single-photon emission computed tomography (SPECT) studies of a variety of neurologic disorders. Although these tracers have been very helpful in diagnosing and guiding treatment of neurologic disease, data describing the distribution and laterality of these tracers in normal resting brain are limited. Advances in quantitative functional imaging have demonstrated the value of using resting studies from control populations as a baseline to account for physiologic fluctuations in cerebral perfusion. Here, we report results from 30 resting Tc-99m ECD SPECT scans and 14 resting Tc-99m HMPAO scans of normal volunteers with no history of neurologic disease. Scans were analyzed with regions of interest and with statistical parametric mapping, with comparisons performed laterally (left vs. right), as well as for age, gender, and handedness. The results show regions of significant asymmetry in the normal controls affecting widespread areas in the cerebral hemispheres, but most marked in superior parietotemporal region and frontal lobes. The results have important implications for the use of normal control SPECT images in the evaluation of patients with neurologic disease.

Prognostic value of 18F-fluorodeoxyglucose-positron emission tomography in patients with differentiated thyroid carcinoma and circulating antithyroglobulin autoantibodies.

OBJECTIVE: To explore the prognostic value of F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) in radioiodine-negative patients with differentiated follicular cell-derived thyroid carcinoma with circulating antithyroglobulin autoantibodies (TgAb). METHODS: We retrospectively reviewed cases of all patients with differentiated thyroid cancer and increased TgAb referred for FDG-PET at Mayo Clinic, Rochester, Minnesota, from August 2001 to December 2004. PET findings were compared with results of other imaging and laboratory studies. Follow-up information was recorded until 19 December 2009. RESULTS: Of the 17 patients identified, PET results were true positive in 10 and false negative in two. In eight of these 12 patients with confirmed residual or recurrent disease, the increased TgAb level persisted and the disease progressed. In four of the 12 patients, TgAb decreased or disappeared after further treatment. In five patients, no residual or recurrent disease was found during follow-up. PET results were true negative in these five patients; TgAb disappeared spontaneously in four of these patients. CONCLUSIONS: Negative PET results were associated with the absence of active disease and disappearing TgAb over time. FDG-avid residual lesions were associated with more aggressive disease and persistently increased TgAb.

Symptom improvement after upgrade from right ventricular apical to biventricular pacing: Role of right and left ventricular volumes assessed with single-photon emission computed tomographic equilibrium radionuclide angiocardiography.

BACKGROUND: In patients with heart failure and reduced left ventricular ejection fraction (LVEF), the effect of upgrading from right ventricular (RV) apical to biventricular pacing on RV and left ventricular (LV) volumes and ejection fraction (EF) is unknown. Also, the relationship of symptom improvement after biventricular upgrade to RV and LV volumes and EF has not been clarified. METHODS AND RESULTS: Nineteen patients with long-standing persistent RV apical pacing who had heart failure symptoms and echocardiographic LVEF of 0.40 or less underwent upgrade to biventricular pacing. Patients had single-photon emission computed tomographic equilibrium radionuclide angiocardiography immediately before and at 3-6 months after the upgrade procedure, to measure RV and LV volumes and EF. Biventricular upgrade was associated with increase in LVEF and decrease in LV end-diastolic and end-systolic volumes; right ventricular ejection fraction (RVEF) and end-diastolic and end-systolic volumes were unaltered. Patients with improvement in New York Heart Association heart failure class of I or more had larger initial LV end-diastolic volumes than patients without an improvement and had decreased LV end-diastolic and end-systolic volumes comparatively. Symptom improvement was not associated with RVEF and volume change. CONCLUSION: Symptom improvement with LV remodeling, but not RV remodeling, occurs 3-6 months after biventricular upgrade in patients with heart failure.