The prognostic value of diastolic and systolic mechanical left ventricular dyssynchrony among patients with coronary artery disease and heart failure.

BACKGROUND: Prevalence and prognostic value of diastolic and systolic dyssynchrony in patients with coronary artery disease (CAD) + heart failure (HF) or CAD alone are not well understood. METHODS: We included patients with gated single-photon emission computed tomography (GSPECT) myocardial perfusion imaging (MPI) between 2003 and 2009. Patients had at least one major epicardial obstruction ≥ 50%. We assessed the association between dyssynchrony and outcomes, including all-cause and cardiovascular death. RESULTS: Of the 1294 patients, HF was present in 25%. Median follow-up was 6.7 years (IQR 4.9-9.3) years with 537 recorded deaths. Patients with CAD + HF had a higher incidence of dyssynchrony than patients with CAD alone (diastolic BW 28.8% for the HF + CAD vs 14.7% for the CAD alone). Patients with CAD + HF had a lower survival than CAD alone at 10 years (33%; 95% CI 27-40 vs 59; 95% CI 55-62, P < 0.0001). With one exception, HF was found to have no statistically significant interaction with dyssynchrony measures in unadjusted and adjusted survival models. CONCLUSIONS: Patients with CAD + HF have a high prevalence of mechanical dyssynchrony as measured by GSPECT MPI, and a higher mortality than CAD alone. However, clinical outcomes associated with mechanical dyssynchrony did not differ in patients with and without HF.

Long-Term Outcomes of 125 Patients With Metastatic Pheochromocytoma or Paraganglioma Treated With 131-I MIBG.

CONTEXT: Prognosis of metastatic pheochromocytoma/paraganglioma following 131-Iodine metaiodobenzylguanidine (MIBG) is incompletely characterized due to small samples and shorter follow-up in these rare, often indolent tumors. OBJECTIVE: To describe long-term survival, frequency, and prognostic impact of imaging, biochemical, and symptomatic response to 131-I MIBG. DESIGN: Retrospective chart and imaging review at a tertiary referral center. PATIENTS: Six hundred sixty-eight person-years of follow-up in 125 patients with metastatic pheochromocytoma/paraganglioma with progression through prior multimodal treatment. INTERVENTION: Median 18 800 MBq 131-I MIBG. MAIN OUTCOME MEASURES: Overall survival, Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST) imaging response, symptomatic response per chart review, and biochemical response (20% change over 2 consecutive assays of catecholamines, vanillylmandelic acid, metanephrines, or chromogranin A). RESULTS: Median survival standard deviation [SD] from diagnosis was 11.5 years [2.4]; following metastasis, 6.5 years [0.8]; post treatment, 4.3 years [0.7]. Among 88 participants with follow-up imaging, 1% experienced complete response, 33% partial response, 53% stability, and 13% progression. Fifty-one percent showed subsequent progression, median progression-free survival [SD] of 2.0 years [0.6]. Stability/response vs progression at first imaging follow-up (3-6 months) predicted improved survival, 6.3 vs 2.4 years (P = 0.021). Fifty-nine percent of 54 patients demonstrated biochemical response. Fifty percent of these relapsed, with median time to laboratory progression [SD] of 2.8 years [0.7]. Biochemical response did not predict extended survival. Seventy-five percent of 83 patients reported improvement in pretreatment symptoms, consisting primarily of pain (42%), fatigue (27%), and hypertension (14%). Sixty-one percent of these patients experienced subsequent symptomatic progression at median [SD] 1.8 years [0.4]. Symptomatic response did not predict extended survival. CONCLUSIONS: Imaging, symptomatic, and laboratory response to multimodal treatment including high-dose 131-I MIBG were achieved on long-term follow-up in metastatic pheochromocytoma or paraganglioma. Imaging response at 3 to 6 months was prognostic.

Molecular Imaging and Therapy for Neuroendocrine Tumors.

OPINION STATEMENT: Neuroendocrine tumors (NETs) are relatively rare, with 12,000-15,000 new cases diagnosed annually in the USA. Although NETs are a diverse group of neoplasms, they share common molecular targets that can be exploited using nuclear medicine techniques for both imaging and therapy. NETs have traditionally been imaged with SPECT imaging using 111In-labeled octreotide analogs to detect neoplasms with somatostatin receptors. In addition, certain NETs (pheochromocytomas, paragangliomas, and neuroblastomas) are also effectively imaged using 123I- or 131I-labeled metaiodobenzylguanidine (MIBG), an analog of guanethidine. More recently, PET imaging with 68Ga-labeled somatostatin receptor (SSR) analogs allows neuroendocrine tumors to be imaged with much higher sensitivity. 68Ga-DOTATATE was approved as a PET tracer by the FDA in June 2016. In addition to imaging, both MIBG and DOTATATE can be labeled with therapeutic radionuclides to deliver targeted radiation selectively to macroscopic and microscopic tumor sites. The incorporation of the same molecular probe for imaging and therapy provides a radio-theranostic approach to identifying, targeting, and treating tumors. Over the years, several centers have experience treating NETs with high-dose 131I-MIBG. 177Lu-DOTATATE was approved by the FDA in 2018 for treatment of gastroenteropancreatic NETs and constitutes a major advancement in the treatment of these diseases. In this paper, we provide an overview of imaging and treating neuroendocrine tumors using MIBG and SSR probes. Although uncommon, neuroendocrine tumors have provided the largest experience for targeted radionuclide imaging and therapy (with the exception of radioiodine treatment for thyroid disease). In addition to benefitting patients with these rare tumors, the knowledge gained provides a blueprint for the development of future paired diagnostic/therapeutic probes for treating other diseases, such as prostate cancer.

Trends in cardiorespiratory fitness: The evolution of exercise treadmill testing at a single Academic Medical Center from 1970 to 2012.

OBJECTIVE: To identify temporal trends in the use of exercise treadmill testing (ETT) and cardiorespiratory fitness (CRF) estimated by ETT in metabolic equivalents (METs). PATIENTS AND METHODS: We compiled an ETT database of all available treadmill tests-including those with concomitant stress echocardiography and nuclear perfusion imaging studies-performed at Duke University Hospital from January 1, 1970- December 31, 2012. Six different ramp protocols were used in these combined modalities. CRF at maximal exertion was estimated using established metrics. Eligible patients were required to have no missing data on maximal treadmill speed, grade, and protocol. RESULTS: The most commonly used ETT protocol was the Bruce (n = 28,877), followed by manual test (n = 7390). Since the 1980's, the use of ETT for clinical purposes declined substantially; there was a decreased trend in utilization of 9.4% over the decades 1990-1999 and 2000-2009. When standard protocol (Bruce) was assessed in isolation, trends in CRF decreased progressively from 1970 to 2012 (mean METs (standard deviation): 11.7 (4.3) to 10.5 (3.5)). After adjusting for baseline comorbidities, the trend was reduced to a lesser degree. CONCLUSIONS: The use of ETT at our institution has declined over time, perhaps due to changes in clinical practice. In patients undergoing ETT using the standard Bruce protocol, CRF decreased progressively over the last five decades. Future studies are needed to clarify the etiology of the decrease in use of such a powerful predictor of clinical outcomes in our medical care environment.

The Prognostic Value of Diastolic and Systolic Mechanical Left Ventricular Dyssynchrony Among Patients With Coronary Heart Disease.

OBJECTIVES: The goal of this study was to examine whether diastolic dyssynchrony, measured by using gated single-photon emission computed tomography (GSPECT) myocardial perfusion imaging (MPI) in patients with coronary artery disease (CAD), is independently associated with adverse outcomes. BACKGROUND: Systolic left ventricular dyssynchrony is known to be associated with worse clinical outcome in patients with CAD. METHODS: This study included patients who presented to Duke University for GSPECT MPI between 2003 and 2009. Patients had at least 1 major epicardial obstruction ≥50%. Dyssynchrony was assessed by using Emory Cardiac Toolbox software and compared with a control population without CAD. Abnormal degree of diastolic/systolic dyssynchrony was defined as values above 2 SDs above mean of mechanical dyssynchrony parameters. Using Cox proportional hazards modeling, the adjusted association between dyssynchrony and outcomes, including all-cause and cardiovascular death, was assessed. RESULTS: Among 1,310 patients with a median age of 64 years (interquartile range: 55 to 72 years), 69.7% were male and 2.6% had left bundle branch block. Overall, 241 (18.4%) and 238 (18.2%) patients had significant systolic and diastolic mechanical dyssynchrony, respectively, and 211 (16.1%) had both. After a median follow-up of 7.1 years, 543 deaths occurred. At 5 years, the mortality estimate was 21.2% among patients with a normal degree of diastolic left ventricular mechanical dyssynchrony (LVMD) and 41.7% among those with an abnormal degree of LVMD (p < 0.001). When added to clinical comorbidities, electrical dyssynchrony, and systolic LVMD, diastolic dyssynchrony was incrementally associated with cardiovascular mortality (global chi-square statistic of 211.9 vs. 222.8; 2 degrees of freedom; p = 0.004). In a model that also includes left ventricular ejection fraction, the addition of diastolic dyssynchrony to systolic dyssynchrony maintained an incremental prognostic benefit (global chi-square statistic of 234.8 vs. 241.8; p = 0.030). Adjustment for baseline ischemia and scar burden did not change this relationship. CONCLUSIONS: Systolic and diastolic left ventricular dyssynchrony, as measured by using GSPECT MPI, were associated with adverse outcomes. Moreover, diastolic dyssynchrony appears to provide incremental predictive value to clinical history, electrical dyssynchrony, and left ventricular function.

Predictors of Survival in 211 Patients with Stage IV Pulmonary and Gastroenteropancreatic MIBG-Positive Neuroendocrine Tumors Treated with 131I-MIBG.

This retrospective analysis identifies predictors of survival in a cohort of patients with meta-iodobenzylguanidine (MIBG)-positive stage IV pulmonary and gastroenteropancreatic neuroendocrine tumor (P/GEP-NET) treated with 131I-MIBG therapy, to inform treatment selection and posttreatment monitoring. Methods: Survival, symptoms, imaging, and biochemical response were extracted via chart review from 211 P/GEP-NET patients treated with 131I-MIBG between 1991 and 2014. For patients with CT follow-up (n = 125), imaging response was assessed by RECIST 1.1 if images were available (n = 76) or by chart review of the radiology report if images could not be reviewed (n = 49). Kaplan-Meier analysis and Cox multivariate regression estimated survival and progression-free survival benefits predicted by initial imaging, biochemical response, and symptomatic response. Results: All patients had stage IV disease at the time of treatment. Median survival was 29 mo from the time of treatment. Symptomatic response was seen in 71% of patients, with the median duration of symptomatic relief being 12 mo. Symptomatic response at the first follow-up predicted a survival benefit of 30 mo (P < 0.001). Biochemical response at the first clinical follow-up was seen in 34% of patients, with stability of laboratory values in 48%; response/stability versus progression extended survival by 40 mo (P < 0.03). Imaging response (20% of patients) or stability (60%) at the initial 3-mo follow-up imaging extended survival by 32 mo (P < 0.001). Additionally, multiple 131I-MIBG treatments were associated with 24 mo of additional survival (P < 0.05). Conclusion: Therapeutic 131I-MIBG for metastatic P/GEP-NETs appears to be an effective means of symptom palliation. Imaging, biochemical, and symptomatic follow-up help prognosticate expected survival after 131I-MIBG therapy. Multiple rounds of 131I-MIBG are associated with prolonged survival.

Correction to: Clinical Quantification of Myocardial Blood Flow Using PET: Joint Position Paper of the SNMMI Cardiovascular Council and the ASNC.

The above position statement originally published containing errors in the author metadata; specifically, the Expert Content Reviewers-Andrew Einstein, Raymond Russell and James R. Corbett-were tagged as full authors of the paper. The article metadata has now been corrected to remove Drs. Einstein, Russell and Corbett from the author line, and the PubMed record has been updated accordingly.

18F-florbetapir Positron Emission Tomography-determined Cerebral ß-Amyloid Deposition and Neurocognitive Performance after Cardiac Surgery.

BACKGROUND: Amyloid deposition is a potential contributor to postoperative cognitive dysfunction. The authors hypothesized that 6-week global cortical amyloid burden, determined by F-florbetapir positron emission tomography, would be greater in those patients manifesting cognitive dysfunction at 6 weeks postoperatively. METHODS: Amyloid deposition was evaluated in cardiac surgical patients at 6 weeks (n = 40) and 1 yr (n = 12); neurocognitive function was assessed at baseline (n = 40), 6 weeks (n = 37), 1 yr (n = 13), and 3 yr (n = 9). The association of 6-week amyloid deposition with cognitive dysfunction was assessed by multivariable regression, accounting for age, years of education, and baseline cognition. Differences between the surgical cohort with cognitive deficit and the Alzheimer's Disease Neuroimaging Initiative cohorts (normal and early/late mild cognitive impairment) was assessed, adjusting for age, education, and apolipoprotein E4 genotype. RESULTS: The authors found that 6-week abnormal global cortical amyloid deposition was not associated with cognitive dysfunction (13 of 37, 35%) at 6 weeks postoperatively (median standard uptake value ratio [interquartile range]: cognitive dysfunction 0.92 [0.89 to 1.07] vs. 0.98 [0.93 to 1.05]; P = 0.455). In post hoc analyses, global cortical amyloid was also not associated with cognitive dysfunction at 1 or 3 yr postoperatively. Amyloid deposition at 6 weeks in the surgical cohort was not different from that in normal Alzheimer's Disease Neuroimaging Initiative subjects, but increased over 1 yr in many areas at a rate greater than in controls. CONCLUSIONS: In this study, postoperative cognitive dysfunction was not associated with 6-week cortical amyloid deposition. The relationship between cognitive dysfunction and regional amyloid burden and the rate of postoperative amyloid deposition merit further investigation.

Variability in Ejection Fraction Measured By Echocardiography, Gated Single-Photon Emission Computed Tomography, and Cardiac Magnetic Resonance in Patients With Coronary Artery Disease and Left Ventricular Dysfunction.

Importance: Clinical decisions are frequently based on measurement of left ventricular ejection fraction (LVEF). Limited information exists regarding inconsistencies in LVEF measurements when determined by various imaging modalities and the potential impact of such variability. Objective: To determine the intermodality variability of LVEF measured by echocardiography, gated single-photon emission computed tomography (SPECT), and cardiovascular magnetic resonance (CMR) in patients with left ventricular dysfunction. Design, Setting, and Participants: International multicenter diagnostic study with LVEF imaging performed at 127 clinical sites in 26 countries from July 24, 2002, to May 5, 2007, and measured by core laboratories. Secondary study of clinical diagnostic measurements of LVEF in the Surgical Treatment for Ischemic Heart Failure (STICH), a randomized trial to identify the optimal treatment strategy for patients with LVEF of 35% or less and coronary artery disease. Data analysis was conducted from March 19, 2016, to May 29, 2018. Main Outcomes and Measures: At baseline, most patients had an echocardiogram and subsets of patients underwent SPECT and/or CMR. Left ventricular ejection fraction was measured by a core laboratory for each modality independent of the results of other modalities, and measurements were compared among imaging methods using correlation, Bland-Altman plots, and coverage probability methods. Association of LVEF by each method and death was assessed. Results: A total of 2032 patients (mean [SD] age, 60.9 [9.6] years; 1759 [86.6%] male) with baseline LVEF data were included. Correlation of LVEF between modalities was r = 0.601 (for biplane echocardiography and SPECT [n = 385]), r = 0.493 (for biplane echocardiography and CMR [n = 204]), and r = 0.660 (for CMR and SPECT [n = 134]). Bland-Altman plots showed only moderate agreement in LVEF measurements from all 3 core laboratories with no substantial overestimation or underestimation of LVEF by any modality. The percentage of observations that fell within a range of 5% ranged from 43% to 54% between different imaging modalities. Conclusions and Relevance: In this international multicenter study of patients with coronary artery disease and reduced LVEF, there was substantial variation between modalities in LVEF determination by core laboratories. This variability should be considered in clinical management and trial design. Trial Registration: Clinicaltrials.gov Identifier: NCT00023595.