Issues with the European Pharmacopoeia Quality Control Method for 99mTc-Labelled Macroaggregated Albumin.

Technetium-99m macroaggregated albumin ([99mTc]Tc-MAA) is an injectable radiopharmaceutical used in nuclear medicine for lung perfusion scintigraphy. After changing to a new batch of macroaggregated albumin (MAA), we saw unwanted uptake in the liver and spleen. The batch was therefore tested by both the supplier and us and we found it to comply with the requirements of the European Pharmacopoeia (Ph. Eur.). However, a simple comparison between the problematic batch and a batch supplied by another manufacturer showed that there was a significant difference. The quality testing showed a higher number of small particles in the problem encumbered MAA batch with unwanted in vivo uptake. In this article we present a simple method of testing for particle size of [99mTc]Tc-MAA, which gives a good indication of how the radioactive drug performs in vivo. We argue that the quality control method described in the Ph. Eur. should be changed. The changes will improve concordance between the laboratory analyzes and what is seen in vivo in human lung perfusion scintigraphy. Furthermore, we hope that the MAA suppliers without delay will replace their release procedure to be in accordance with the method described in this article.

High osteoprotegerin levels predict MACCE in STEMI patients, but are not associated with myocardial salvage.

OBJECTIVES: High circulating levels of osteoprotegerin (OPG) carry prognostic impact in cohorts with various cardiovascular diagnoses. With the present study, we aim to investigate the role of OPG within the scale of myocardial damage. DESIGN: This study includes 219 consecutive patients with acute ST-elevation myocardial infarction randomized to primary percutaneous coronary intervention (pPCI) or pPCI and remote ischemic per-conditioning. Salvage index via myocardial single-photon emission CT assessment (data available in 61% of the patients) was performed, and derived from Day 1 (myocardial area at risk) and Day 30 (final infarct size). Plasma OPG levels were measured using an in-house immunoassay. A combined end-point of all-mortality, myocardial infarction, stroke, readmission for heart failure and ischemic stroke/transient ischemic attack (Major Adverse Cardiac and Cerebrovascular Events [MACCE]) was used for follow-up; 45 (38-48 months). RESULTS: High OPG levels were associated with the severity of cardiovascular disease. During follow-up, OPG was a predictor of MACCE (unadjusted, HR: 2.1, 95% CI: 1.14-3.85, P = 0.017). Adjustments for age, gender, and body mass index preserved the independent predictive power of OPG. However, OPG levels were neither associated with salvage index nor with the final infarct size. Remote ischemic per-conditioning had no effect on OPG levels. CONCLUSION: Despite absent association between OPG levels and the scale of myocardial damage, high OPG levels predict a significantly increased risk of MACCE.

Pre-hospital evaluation of electrocardiographic grade 3 ischemia predicts infarct progression and final infarct size in ST elevation myocardial infarction patients treated with primary percutaneous coronary intervention.

BACKGROUND: In STEMI, grade-3 ischemia (G3) on admission ECG predicts larger infarct size (IS) than grade-2 (G2). We evaluated whether pre-hospital G3 and its temporal behavior are associated with IS and salvage after pPCI. METHODS: In 401 STEMI patients, pre-hospital and pre-PCI ECGs were classified as G3 or G2. IS was assessed by single-photon emission computed tomography (SPECT) at 30days. In 245 patients, pre-PCI SPECT was available to determine myocardium at risk (MaR). RESULTS: G3 criteria were met by 88, and G2 by 313 patients. G3 was independently associated with IS (p=0.006). With ST resolution (STR) group as a reference, G2->G2, G2->G3 and G3->G3 were associated with larger IS (B=4.4, p=0.004; B=5.4, p=0.01; B=10.2, p<0.001, respectively), whereas G3->G2 was not. Salvage was similar between G3 and G2 on pre-hospital ECG if treated early, however lower for G3 when treated later (>2.5h); 48% (35-78) vs 62% (40-87); p=0.04. CONCLUSION: Development or persistence of G3 is associated with larger IS and less salvage, but decreasing grade G3->G2 was not.

Complete somatostatin-induced insulin suppression combined with heparin loading does not significantly suppress myocardial 18F-FDG uptake in patients with suspected cardiac sarcoidosis.

BACKGROUND: Cardiac 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography preceded by extended fasting is used to demonstrate active cardiac sarcoidosis. However, physiological insulin-dependent myocardial 18F-FDG uptake often obscures 18F-FDG uptake in sarcoid lesions. We therefore aimed to completely suppress physiological myocardial 18F-FDG uptake by pharmaceutically blocking endogenous insulin secretion while elevating free fatty acids (FFAs). METHODS AND RESULTS: Six patients with suspected cardiac sarcoidosis were studied in a randomized cross-over design: (1) 12 hours fasting followed by 2 hours saline infusion (SALINE), and (2) 12 hours fasting followed by 2 hour infusions of somatostatin (300 µg/hour) and heparin (70 mIE/kg/minutes) (SOMA). 18F-FDG PET scans were performed post-infusion. Glucose, insulin, and FFA levels were measured and left ventricle SUV-values were recorded. During the SALINE infusion, insulin, glucose, and FFAs remained stable. By design, the SOMA infusions rapidly (<60 minutes) suppressed insulin completely, while FFA levels peaked at 1.13 ± 0.23 mM. However, SOMA infusions only suppressed cardiac 18F-FDG uptake insignificantly globally [SUVmean (g/mL): 4.0 ± 3.3 (SALINE) vs 2.4 ± 1.2 (SOMA), P = .15] and regionally. CONCLUSIONS: Complete insulin suppression combined with markedly increased circulating FFAs does not completely suppress physiological myocardial 18F-FDG uptake and thus conveys no extra diagnostic value compared with extended fasting.

Global longitudinal strain by speckle tracking for infarct size estimation.

AIMS: To assess the utility of speckle tracking global longitudinal systolic strain (GLS) compared with traditional echocardiographic indices including left ventricular ejection fraction (LVEF), wall motion score index (WMSI), and end-systolic volume index (ESVI), in estimating the infarct size (IS) following a ST-elevation myocardial infarction (STEMI). METHODS AND RESULTS: The study includes 227 patients with STEMI and day 1 and day 30 echocardiograms, and myocardial perfusion imaging (MPI) only at day 30 to assess IS. IS was modelled by linear regression with echocardiographic parameters using MPI as reference. Resulting echocardiographic IS estimates were compared by ratios of standard deviations of model residuals (RSD). To estimate the resultant day 30 IS 1 day after a STEMI, GLS was more precise than LVEF (RSD: 0.91, P = 0.014) and ESVI (RSD: 0.88, P = 0.002), and comparable with WMSI (RSD 0.99, P = 0.86). To estimate IS from a day 30 echocardiogram, GLS was comparable with LVEF (RSD: 0.98, P = 0.68) and ESVI (RSD: 1.04, P = 0.40), but WMSI was more precise (RSD: 0.89, P = 0.006). Multiple linear regression revealed that on day 1 after STEMI, GLS significantly complemented the standard parameters separately (P-values all models <0.001) or combined [multivariable model: GLS (P = 0.001), WMSI (P = 0.03), LVEF (P = 0.40)]. On day 30, GLS significantly complemented LVEF and ESVI, but when WMSI was in the model, GLS's association with IS was not significant. CONCLUSION: On day 1 after revascularization for STEMI, GLS contains additional information about final IS compared with standard echocardiographic systolic function indices. Studies are needed to clarify whether this has prognostic implications.

Suppression of circulating free fatty acids with acipimox in chronic heart failure patients changes whole body metabolism but does not affect cardiac function.

Circulating free fatty acids (FFAs) may worsen heart failure (HF) due to myocardial lipotoxicity and impaired energy generation. We studied cardiac and whole body effects of 28 days of suppression of circulating FFAs with acipimox in patients with chronic HF. In a randomized double-blind crossover design, 24 HF patients with ischemic heart disease [left ventricular ejection fraction: 26 ± 2%; New York Heart Association classes II (n = 13) and III (n = 5)] received 28 days of acipimox treatment (250 mg, 4 times/day) and placebo. Left ventricular ejection fraction, diastolic function, tissue-Doppler regional myocardial function, exercise capacity, noninvasive cardiac index, NH(2)-terminal pro-brain natriuretic peptide (NT-pro-BNP), and whole body metabolic parameters were measured. Eighteen patients were included for analysis. FFAs were reduced by 27% in the acipimox-treated group [acipimox vs. placebo (day 28-day 0): -0.10 ± 0.03 vs. +0.01 ± 0.03 mmol/l, P < 0.01]. Glucose and insulin levels did not change. Acipimox tended to increase glucose and decrease lipid utilization rates at the whole body level and significantly changed the effect of insulin on substrate utilization. The hyperinsulinemic euglycemic clamp M value did not differ. Global and regional myocardial function did not differ. Exercise capacity, cardiac index, systemic vascular resistance, and NT-pro-BNP were not affected by treatment. In conclusion, acipimox caused minor changes in whole body metabolism and decreased the FFA supply, but a long-term reduction in circulating FFAs with acipimox did not change systolic or diastolic cardiac function or exercise capacity in patients with HF.

Cardiovascular and metabolic effects of 48-h glucagon-like peptide-1 infusion in compensated chronic patients with heart failure.

The incretin hormone glucagon-like peptide-1 (GLP-1) and its analogs are currently emerging as antidiabetic medications. GLP-1 improves left ventricular ejection fraction (LVEF) in dogs with heart failure (HF) and in patients with acute myocardial infarction. We studied metabolic and cardiovascular effects of 48-h GLP-1 infusions in patients with congestive HF. In a randomized, double-blind crossover design, 20 patients without diabetes and with HF with ischemic heart disease, EF of 30 +/- 2%, New York Heart Association II and III (n = 14 and 6) received 48-h GLP-1 (0.7 pmol.kg(-1).min(-1)) and placebo infusion. At 0 and 48 h, LVEF, diastolic function, tissue Doppler regional myocardial function, exercise testing, noninvasive cardiac output, and brain natriuretic peptide (BNP) were measured. Blood pressure, heart rate, and metabolic parameters were recorded. Fifteen patients completed the protocol. GLP-1 increased insulin (90 +/- 17 pmol/l vs. 69 +/- 12 pmol/l; P = 0.025) and lowered glucose levels (5.2 +/- 0.1 mmol/l vs. 5.6 +/- 0.1 mmol/l; P < 0.01). Heart rate (67 +/- 2 beats/min vs. 65 +/- 2 beats/min; P = 0.016) and diastolic blood pressure (71 +/- 2 mmHg vs. 68 +/- 2 mmHg; P = 0.008) increased during GLP-1 treatment. Cardiac index (1.5 +/- 0.1 l.min(-1).m(-2) vs. 1.7 +/- 0.2 l.min(-1).m(-2); P = 0.54) and LVEF (30 +/- 2% vs. 30 +/- 2%; P = 0.93), tissue Doppler indexes, body weight, and BNP remained unchanged. Hypoglycemic events related to GLP-1 treatment were observed in eight patients. GLP-1 infusion increased circulating insulin levels and reduced plasma glucose concentration but had no major cardiovascular effects in patients without diabetes but with compensated HF. The impact of minor increases in heart rate and diastolic blood pressure during GLP-1 infusion requires further studies. Hypoglycemia was frequent and calls for caution in patients without diabetes but with HF.

Surveillance With PET/CT and Liquid Biopsies of Stage I-III Lung Cancer Patients After Completion of Definitive Therapy: A Randomized Controlled Trial (SUPER).

Despite increased focus on prevention as well as improved treatment possibilities, lung cancer remains among the most frequent and deadliest cancer diagnoses worldwide. Even lung cancer patients treated with curative intent have a high risk of relapse, leading to a dismal prognosis. More knowledge on the efficacy of surveillance with both current and new technologies as well as on the impact on patient treatment, quality of life, and survival are urgently needed. We therefore designed a randomized phase 3 trial. In one arm, every other computed tomography (CT) scan is replaced by positron emission tomography/CT, the other arm is the standard follow-up scheme with CT. The standard arm is identical to the current national Danish follow-up program. The primary endpoint is to compare the number of relapses treatable with curative intent in the 2 arms. We aim to include 750 patients over a 3-year period. Additionally, we will test the feasibility of noninvasive lung cancer diagnostics and surveillance in the form of circulating tumor DNA analysis. For this purpose, blood samples are collected before treatment and at each following control. The blood samples are stored in a biobank for later analysis and will not be used for guiding patient treatment decisions.

Sentinel lymph-node biopsy in patients with squamous cell carcinoma of the penis.

OBJECTIVES: To evaluate a single-centre experience with sentinel lymph-node biopsy (SLNB) as a staging procedure in patients with squamous cell carcinoma (SCC) of the penis. PATIENTS AND METHODS: The study included 60 patients with SCC of the penis, who had SLNB in all groins where no palpable nodes were found, and in groins with palpable nodes with negative fine-needle aspiration cytology. Lymphoscintigraphy and intraoperative lymph node detection was done using (99m)Tc-nanocolloid and no use of blue dye. RESULTS: In all, there were 97 SLNB procedures in 52 patients; 20 (20.6%) of the SLNB were positive for nodal metastases. Two negative SLNB proved to be false-negative during the observation period. The false negative-rate was 9%, the sensitivity 91% and the negative predictive value 97.5%. Minor early complications occurred after 4% of the SLNB procedures. No major or late complications were recorded. CONCLUSIONS: SLNB is minimally invasive and can be used as a safe and reliable staging procedure in patients with SCC of the penis. Thus standard lymph-node dissection can be avoided in most patients.

Scintigraphic evaluation of routine filterwire distal protection in percutaneous coronary intervention for acute ST-segment elevation myocardial infarction: a randomized controlled trial.

AIM: Distal embolization during primary percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI) may result in reduced myocardial perfusion, infarct extension and impaired prognosis. In a prospective randomized trial, we assessed the effect of routine filterwire distal protection on scintigraphic estimated infarct size. METHODS AND RESULTS: The effect of routine filterwire distal protection was evaluated in 344 patients with STEMI <12 hours undergoing primary PCI. Patients were randomized to distal protection with a filterwire or standard PCI. The primary endpoint was myocardial infarct size measured by Sestamibi SPECT after 30 days (%). Secondary endpoints included myocardial salvage, ST-segment resolution (STR), myocardial biomarker release and major adverse cardiac and cerebral events. Baseline characteristics including area at risk (estimated by Sestamibi SPECT) were similar. Final infarct size was not statistically different in the distal protection and the control groups (median [IQR], 6% [1-19] and 5% [1-14], P = .23). Also, secondary endpoints were similar in the two treatment groups. CONCLUSION: Distal protection with a filterwire performed as routine therapy in primary PCI for STEMI did not reduce myocardial infarct size. The study does not support routine use of distal protection in primary PCI.

ST changes before and during primary percutaneous coronary intervention predict final infarct size in patients with ST elevation myocardial infarction.

BACKGROUND: In patients with ST elevation myocardial infarction (STEMI), spontaneous ST resolution (spontSTR) is a marker of successful microvascular reperfusion. The significance of increase in ST elevation during reperfusion therapy (the ST peak phenomenon), however, is controversial. AIMS: The purpose of the study was to evaluate whether preprocedural and periprocedural ST changes predict final infarct size (IS) in STEMI patients treated with primary percutaneous coronary intervention (primary PCI). METHODS: Twelve-lead electrocardiograms (ECGs) were acquired in the prehospital phase and on admission in 200 STEMI patients transferred for primary PCI. Continuous ST monitoring was performed during and 90 minutes after primary PCI. The exact timing of interventional procedures and the resulting thrombolysis in myocardial infarction (TIMI) flow were registered. A 1-month single-photon emission computerized tomography was performed to evaluate IS. Patients were stratified into groups according to preprocedural and periprocedural ST changes as follows: patients with spontSTR before primary PCI and without (A) or with (B) ST peak during primary PCI and patients with persistent ST elevation before primary PCI and without (C) or with (D) ST peak during primary PCI. FINDINGS: Groups A (n = 45), B (n = 10), C (n = 109), and D (n = 36) differed with regard to IS (median, 2%, 3%, 13% vs 22% of the left ventricle; P < .0001). In multivariable analysis adjusting for baseline characteristics, preprocedural and periprocedural ECG findings and routine angiography findings, spontSTR was associated with smaller IS (B = -8.6%; P < .001), whereas the ST peak phenomenon was associated with larger IS (B = +5.0%; P = .006). There was no difference in TIMI flow grades in relation to coronary interventions among patients with and without ST peak during primary PCI. CONCLUSIONS: In STEMI patients, spontSTR before primary PCI and the ST peak phenomenon during primary PCI predict minor vs extensive IS independent of angiographic patency grades. Further studies are needed to clarify whether the ST peak phenomenon is "a marker of injury before reperfusion" or "a marker of reperfusion-induced injury."

Impact of the Charlson Comorbidity Index score on risk prediction by single-photon emission computed tomography myocardial perfusion imaging following myocardial infarction.

BACKGROUND: Comorbidity is common among patients with myocardial infarction (MI). We examined whether comorbidity level modified the single-photon emission computed tomography myocardial perfusion imaging (SPECT MPI)-based prediction of 5-year risk of MI and all-cause death in patients with MI. METHODS: This cohort study included patients with prior MI having a SPECT MPI at Aarhus University Hospital, Denmark, 1999-2011. Using nationwide registries, we obtained information on comorbidity levels (low, moderate, and severe) and outcomes. We computed risk and hazard ratios (HRs) with 95% confidence intervals (CIs) for MI and all-cause death, comparing normal (no defects) versus abnormal scan (reversible and/or fixed defects) using Cox regression adjusting for sex, age, and comorbidity level. RESULTS: We identified 1,192 patients with MI before SPECT MPI. The 5-year risk for patients with normal versus abnormal scans were 11.7% versus 18.3% for MI, and 8.0% versus 13.2% for all-cause death, respectively. The overall 5-year adjusted HR (aHR) of MI was 1.56 (95% CI: 1.09-2.21), 1.33 (95% CI: 0.82-2.15) with low comorbidity, 1.39 (95% CI: 0.68-2.83) with moderate comorbidity, and 2.53 (95% CI: 1.14-5.62) with severe comorbidity. Similarly, the 5-year aHR for all-cause death was 1.39 (95% CI: 0.90-2.14) overall; 2.33 (95% CI: 0.79-6.84) with low comorbidity, 2.05 (95% CI: 0.69-6.06) with moderate comorbidity, and 1.07 (95% CI: 0.64-1.80) with severe comorbidity. CONCLUSION: We conclude that comorbidity level may modify the 5-year risk prediction associated with an abnormal SPECT MPI scan in patients with previous MI.

Prospective Comparison of FFR Derived From Coronary CT Angiography With SPECT Perfusion Imaging in Stable Coronary Artery Disease: The ReASSESS Study.

OBJECTIVES: This study sought to compare the per-patient diagnostic performance of coronary computed tomography angiography (CTA)-derived fractional flow reserve (FFRCT) with that of single-photon emission computed tomography (SPECT), using a fractional flow reserve (FFR) value of ≤0.80 as the reference for diagnosing at least 1 hemodynamically significant stenosis in a head-to-head comparison of patients with intermediate coronary stenosis as determined by coronary CTA. BACKGROUND: No previous study has prospectively compared the diagnostic performance of FFRCT and myocardial perfusion imaging by SPECT in symptomatic patients with intermediate range coronary artery disease (CAD). METHODS: This study was conducted at a single-center as a prospective study in patients with stable angina pectoris (N = 143). FFRCT and SPECT analyses were performed by core laboratories and were blinded for the personnel responsible for downstream patient management. FFRCT ≤0.80 distally in at least 1 coronary artery with a diameter ≥2 mm classified patients as having ischemia. Ischemia by SPECT was encountered if a reversible perfusion defect (summed difference score ≥2) or transitory ischemic dilation of the left ventricle (ratio >1.19) were found. RESULTS: The per-patient diagnostic performance for identifying ischemia (95% confidence interval [CI]), FFRCT versus SPECT, were sensitivity of 91% (95% CI: 81% to 97%) versus 41% (95% CI: 29% to 55%; p < 0.001); specificity of 55% (95% CI: 44% to 66%) versus 86% (95% CI: 77% to 93%; p < 0.001); negative predictive value of 90% (95% CI: 82% to 98%) versus 68% (95% CI: 59% to 77%; p = 0.001); positive predictive value of 58% (95% CI: 48% to 68%) versus 67% (95% CI: 51% to 82%; p = NS); and accuracy of 70% (95% CI: 62% to 77%) versus 68% (95% CI: 60% to 75%; p = NS) respectively. CONCLUSIONS: In patients with stable chest pain and CAD as determined by coronary CTA, the overall diagnostic accuracy levels of FFRCT and SPECT were identical in assessing hemodynamically significant stenosis. However, FFRCT demonstrated a significantly higher diagnostic sensitivity than SPECT.

Routine thrombectomy in percutaneous coronary intervention for acute ST-segment-elevation myocardial infarction: a randomized, controlled trial.

BACKGROUND: Distal embolization during primary percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction may result in reduced myocardial perfusion, infarct extension, and impaired prognosis. METHODS AND RESULTS: In a prospective randomized trial, we studied the effect of routine thrombectomy in 215 patients with ST-segment-elevation myocardial infarction lasting <12 hours undergoing primary PCI. Patients were randomized to thrombectomy pretreatment or standard PCI. The primary end point was myocardial salvage measured by sestamibi SPECT, calculated as the difference between area at risk and final infarct size determined after 30 days (percent). Secondary end points included final infarct size, ST-segment resolution, and troponin T release. Baseline variables, including ST-segment elevation and area at risk, were similar. Salvage was not statistically different in the thrombectomy and control groups (median, 13% [interquartile range, 9% to 21%] and 18% [interquartile range, 7% to 25%]; P=0.12), but 24 patients in the thrombectomy group and 12 patients in the control group did not have an early SPECT scan, mainly because of poor general or cardiac condition (P=0.04). In the thrombectomy group, final infarct size was increased (median, 15%; [interquartile range, 4% to 25%] versus 8% [interquartile range, 2% to 18%]; P=0.004). CONCLUSIONS: Thrombectomy performed as routine therapy in primary PCI for ST-elevation myocardial infarction does not increase myocardial salvage. The study suggests a possible deleterious effect of thrombectomy, resulting in an increased final infarct size, and does not support the use of thrombectomy in unselected primary PCI patients.

NOGA-guided analysis of regional myocardial perfusion abnormalities treated with intramyocardial injections of plasmid encoding vascular endothelial growth factor A-165 in patients with chronic myocardial ischemia: subanalysis of the EUROINJECT-ONE multicenter double-blind randomized study.

BACKGROUND: The aim of this substudy of the EUROINJECT-ONE double-blind randomized trial was to analyze changes in myocardial perfusion in NOGA-defined regions with intramyocardial injections of plasmid encoding plasmid human (ph)VEGF-A(165) using an elaborated transformation algorithm. METHODS AND RESULTS: After randomization, 80 no-option patients received either active, phVEGF-A165 (n=40), or placebo plasmid (n=40) percutaneously via NOGA-Myostar injections. The injected area (region of interest, ROI) was delineated as a best polygon by connecting of the injection points marked on NOGA polar maps. The ROI was projected onto the baseline and follow-up rest and stress polar maps of the 99m-Tc-sestamibi/tetrofosmin single-photon emission computed tomography scintigraphy calculating the extent and severity (expressed as the mean normalized tracer uptake) of the ROI automatically. The extents of the ROI were similar in the VEGF and placebo groups (19.4+/-4.2% versus 21.5+/-5.4% of entire myocardium). No differences were found between VEGF and placebo groups at baseline with regard to the perfusion defect severity (rest: 69+/-11.7% versus 68.7+/-13.3%; stress: 63+/-13.3% versus 62.6+/-13.6%; and reversibility: 6.0+/-7.7% versus 6.7+/-9.0%). At follow-up, a trend toward improvement in perfusion defect severity at stress was observed in VEGF group as compared with placebo (68.5+/-11.9% versus 62.5+/-13.5%, P=0.072) without reaching normal values. The reversibility of the ROI decreased significantly at follow-up in VEGF group as compared with the placebo group (1.2+/-9.0% versus 7.1+/-9.0%, P=0.016). Twenty-one patients in VEGF and 8 patients in placebo group (P<0.01) exhibited an improvement in tracer uptake during stress, defined as a >or =5% increase in the normalized tracer uptake of the ROI. CONCLUSIONS: Projection of the NOGA-guided injection area onto the single-photon emission computed tomography polar maps permits quantitative evaluation of myocardial perfusion in regions treated with angiogenic substances. Injections of phVEGF A165 plasmid improve, but do not normalize, the stress-induced perfusion abnormalities.

Adaptation of nonrevascularized human hibernating and chronically stunned myocardium to long-term chronic myocardial ischemia.

It is unknown whether human chronically ischemic dysfunctional myocardium degenerates over time or adapts to chronic ischemia. We studied whether perfusion, metabolism, and contractile function and reserve can be preserved in nonrevascularized human chronically stunned and hibernating myocardium. We studied 16 event-free, medically treated patients with ejection fractions of 31 +/- 2% and chronically stunned or hibernating myocardium in 56 +/- 5% of the left ventricle on technetium-99m sestamibi single-photon emission computed tomography/fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography. Patients underwent repeat single-photon emission computed tomography, positron emission tomography, and tissue Doppler echocardiography at rest and during stress at follow-up after 25 +/- 4 months, and we investigated whether measurements of myocardial viability remained stable over time. Patients were stable with respect to New York Heart Association class and global left ventricular function (30 +/- 2%, p = 0.81). Wall motion score was unaltered in hibernating myocardium and chronically stunned regions, and a contractile reserve by tissue Doppler stress echocardiography was preserved. Overall, 74% of hibernating myocardium and chronically stunned regions retained their initial perfusion/metabolism pattern at follow-up. In hibernating myocardium, initial and follow-up sestamibi uptakes (53 +/- 1% and 53 +/- 2%, p = 0.85) and FDG uptakes (76 +/- 1% and 74 +/- 1%, p = 0.21) did not differ. In chronically stunned regions, sestamibi uptake displayed a minor decrease at follow-up (70 +/- 1% vs 67 +/- 1%, p <0.01) and FDG uptake remained constant (68 +/- 2% and 67 +/- 1%, p = 0.21). In conclusion, myocardial perfusion, FDG uptake, and contractile function in nonrevascularized chronically stunned and hibernating myocardium adapt to chronic ischemia in patients who are free of events. In chronically stunned regions, adaptation may be less complete than in hibernating myocardium.

Remote ischaemic conditioning and healthcare system delay in patients with ST-segment elevation myocardial infarction.

OBJECTIVE: We investigated influence of remote ischaemic conditioning (RIC) on the detrimental effect of healthcare system delay on myocardial salvage in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (pPCI). METHODS: A post-hoc analysis of a randomised controlled trial in patients with STEMI randomised to treatment with pPCI or RIC+pPCI. RIC was performed as four cycles of intermittent 5 min upper arm ischaemia and reperfusion. Healthcare system delay was defined as time from emergency medical service call to pPCI-wire. Myocardial salvage index (MSI) was assessed by single photon emission computerised tomography. RESULTS: Data for healthcare system delay and MSI were available for 129 patients. MSI was negatively associated with healthcare system delay in patients treated with pPCI alone (-0.003 decrease in MSI/min of healthcare system delay; 95% CI -0.005 to -0.001, r(2)=0.11, p=0.008) but not in patients treated with RIC+pPCI (-0.0002 decrease in MSI/min of healthcare system delay; 95% CI -0.001 to 0.001, r(2)=0.002, p=0.74). In patients with healthcare system delay ≤120 min, RIC+pPCI did not affect median MSI compared with pPCI alone (0.75 (IQR: 0.49-0.99) and 0.70 (0.45-0.94), p=1.00). However, in patients with healthcare system delay >120 min, RIC+pPCI increased median MSI compared with pPCI alone (0.74 (0.52-0.93) vs 0.42 (0.22-0.68), p=0.02). Adjusting for potential confounders did not affect the results. CONCLUSIONS: RIC as adjunctive to pPCI attenuated the detrimental effect of healthcare system delay on myocardial salvage in patients with STEMI, suggesting that the cardioprotective effect of RIC increases with the duration of ischaemia. TRIAL REGISTRATION NUMBER: NCT00435266; post-results.

Impact of co-morbidity on the risk of first-time myocardial infarction, stroke, or death after single-photon emission computed tomography myocardial perfusion imaging.

The impact of co-morbidity on the cardiovascular risk after single-photon emission computed tomography myocardial perfusion imaging (SPECT MPI) remains unclear. We examined the association between a normal versus abnormal SPECT MPI scan on 10-year risk of myocardial infarction, stroke, and all-cause death, overall and according to co-morbidity level. We identified all patients without previous myocardial infarction or cerebrovascular disease, who had an SPECT MPI performed at Aarhus University Hospital Skejby during 1999 to 2011. We categorized the SPECT MPI scan as normal (no defects) or abnormal (reversible and/or fixed defects). Using nationwide medical registries, we obtained information on co-morbidity level (using Charlson co-morbidity index) and outcomes. We used Cox regression to compute hazard ratios with 95% confidence intervals (CIs), adjusting for gender, age, and co-morbidity level. Among 7,040 patients, 4,962 (70%) had normal scans and 2,078 (30%) abnormal scans. Patients with a normal versus abnormal scan had a 10-year risk of 5.7% versus 10.9% for myocardial infarction, 6.0% versus 7.8% for stroke, and 16.5% versus 29.0% for all-cause death. After adjustment, an abnormal scan was associated with increased risk of myocardial infarction (adjusted hazard ratio 1.73, 95% CI 1.37 to 2.18) and all-cause death (1.42, 95% CI 1.23 to 1.65) but not stroke (1.12, 95% CI 0.86 to 1.45). Co-morbidity level did not affect substantially the association between the scan result and the outcomes. In conclusion, independently of co-morbidity level, an abnormal SPECT MPI scan was associated with an increased 10-year risk of myocardial infarction and all-cause death but not stroke.