Decreased Gray-White Matter Contrast of [11C]-PiB Uptake in Cognitively Unimpaired Subjects with Severe Obstructive Sleep Apnea.

BACKGROUND: Very recently, cognitively normal, middle-aged adults with severe obstructive sleep apnea (OSA) were shown to have regional cortical amyloid-ß deposits. In the normal brain, amyloid tracer (e.g., [11C]-PiB) uptake is observed in white matter (WM) but not in cortical gray matter (GM), resulting in clear GM-WM contrast. There are no reports on possible changes in this contrast in severe OSA. OBJECTIVES: Evaluate changes in the global [11C]-PiB GM-WM contrast and study if factors reflecting clinical and imaging characteristics are associated with them. DESIGN AND SETTING: Cross-sectional imaging study. PARTICIPANTS: 19 cognitively intact middle-aged (mean 44 years) patients with severe OSA (Apnea-Hypopnea Index >30/h), carefully selected to exclude any other possible factors that could alter brain health. MEASUREMENTS: Detailed neuroimaging (amyloid PET, MRI). Signs of possible alterations in amyloid tracer GM-WM contrast and kinetics were studied with static and dynamic [11C]-PiB PET and WM structures with detailed 3.0T MRI. RESULTS: Static [11C]-PiB PET uptake showed significantly decreased GM-WM contrast in 5 out of 19 patients. This was already clearly seen in visual evaluation and also detected quantitatively using retention indexes. Dynamic imaging revealed decreased contrast due to alterations in trace accumulation in the late phase of [11C]-PiB kinetics. Decreased GM-WM contrast in the late phase was global in nature. MRI revealed no corresponding alterations in WM structures. Importantly, decreased GM-WM contrast was associated with smoking (p = 0.007) and higher Apnea-Hypopnea Index (p = 0.001). CONCLUSIONS: Severe OSA was associated with decreased GM-WM contrast in amyloid tracer uptake, with significant correlation with clinical parameters of smoking and AHI. The results support and further extend the current understanding of the deleterious effect of severe OSA on proper amyloid clearance, possibly reflecting dysfunction of the brain glymphatic system.

Myocardial sympathetic nervous dysfunction detected with iodine-123-MIBG is associated with low heart rate variability after myocardial infarction.

UNLABELLED: The association between myocardial sympathetic innervation and heart rate variability after myocardial infarction was studied in a group of 12 men (aged 30-65 yr) 3 mo after their first myocardial infarction. METHODS: Viable myocardium was imaged using 123I-phenylpentadecanoic acid (pPPA). Functioning myocardial sympathetic nervous tissue was imaged using [123I]-metaiodobenzylguanidine (MIBG). Heart rate variability was measured as the ratio of maximum-to-minimum RR intervals in ECG during deep breathing. RESULTS: The patients were divided into normal (n = 6) and low (n = 6) heart rate variability groups. Myocardial infarction size (pPPA defect) was comparable in the normal and low heart rate variability groups. Even the MIBG defect size was not significantly different in the normal and low groups, the portion of viable myocardium with impaired sympathetic innervation (MIBG defect minus pPPA defect) was significantly greater in the low heart rate variability group than in the normal group. CONCLUSION: The extent of viable myocardium with disturbed sympathetic innervation was greater in patients with low heart rate variability as compared to those with normal heart rate variability 3 mo after myocardial infarction.

Haemodynamic effects of acetazolamide in patients with cardiovascular disorders: correlation with calculated cerebral perfusion reserve.

Individual responses of cerebral blood flow to acetazolamide are highly variable. We hypothesized that this may be due to interactions with cardiovascular diseases and medication. Therefore, we measured the haemodynamic effects of acetazolamide in patients with various cardiovascular disorders and evaluated whether these had any correlation with calculated cerebral perfusion reserve. Ten male patients aged 58 +/- 9 years (mean +/- S.D.) were studied with first-pass radionuclide ventriculography and echocardiography before and 20 min after the administration of 1 g acetazolamide. Systolic blood pressure fell from 133 +/- 21 to 128 +/- 19 mmHg (P < 0.05) and the cardiac output to total blood volume ratio increased from 0.85 +/- 0.18 to 0.92 +/- 0.11 (P = 0.05), indicating a 14% reduction in peripheral vascular resistance. In a further study, 15 patients aged 60 +/- 7 years (22 studies) were studied simultaneously with a nuclear stethoscope and 99Tc(m)-hexamethylpropyleneamine oxime single photon emission tomography before and after acetazolamide administration. The cardiac output ratio increased from 0.81 +/- 0.17 to 0.89 +/- 0.17 (P < 0.05) and showed a significant inverse correlation with calculated cerebral perfusion reserve. In conclusion, acetazolamide increases the cardiac output ratio and reduces systolic blood pressure, indicating reduced peripheral vascular resistance in patients with various cardiovascular diseases and medication. The increase in the cardiac output ratio is inversely related with calculated cerebral perfusion reserve. This helps to explain the high individual variability in calculated cerebral perfusion reserve.

Are three-dimensional surface-shaded SPET images better than planar and coronal SPET images in the assessment of regional pulmonary perfusion?

Although single photon emission tomographic (SPET) imaging has been shown to be more sensitive than planar imaging in the diagnosis of pulmonary embolism, it has yet to be used routinely in clinical practice. The aims of this study were (1) to compare a new three-dimensional surface-shaded version of SPET (3-D SPET) with conventional planar imaging and coronal SPET slices, and (2) to evaluate observer agreement among these three modalities in the assessment of regional pulmonary perfusion. Compared with a consensus score (based on revised PIOPED criteria) of 29 cases, including nine with a clinical diagnosis of pulmonary embolism, 3-D SPET showed the highest number of normal scans, suggesting better specificity than planar or coronal SPET images. Five observers evaluated the three image sets twice within a 3-6 month period. Agreement with the consensus score was slightly better for the second reading and the average perfect agreement was 71-76%. No one image set was superior to any other in this respect. In conclusion, the number of normal scans using 3-D SPET is significantly greater relative to planar and coronal SPET scans as defined by the consensus view. Observer agreement rates are very similar with all three modalities.

Effect of radiochemical purity of 99Tcm-Q12 on myocardial SPET image quality.

In myocardial perfusion SPET studies with 99Tcm-Q12, we observed that some patients had high liver uptake that interfered significantly in the assessment of the inferior wall. The aim of this study was to assess the effects of the radiochemical purity of 99Tcm-Q12 on liver uptake. Thirty-one patients undergoing routine myocardial infarction perfusion studies were evaluated. The radiochemical purity of 99Tcm-Q12 was determined using HPLC. Venous blood samples taken 50 min after injection of 99Tcm-Q12 during peak exercise were also analysed. Liver uptake was expressed as the liver-to-heart ratio. In addition, the SPET images were classified by two experienced nuclear medicine specialists into three groups representing high-quality images (n = 7), images with high general background activity (n = 13) and images with high liver and/or intestinal uptake (n = 11). The liver-to-heart ratio correlated inversely with the radiochemical purity of 99Tcm-Q12 (r = -0.65, P < 0.001) and unchanged 99Tcm-Q12 in plasma (r = -0.44, P < 0.02). The radiochemical purity of 99Tcm-Q12 was significantly lower in the group with high liver uptake (60.1 +/- 4.2%) than in the group with good-quality images (81.8 +/- 5.6%, P < 0.01) or with high background activity (82.3 +/- 2.5%, P < 0.01). In conclusion, the radiochemical purity of 99Tcm-Q12 has a significant inverse correlation with the liver-to-heart ratio; thus, the high radiochemical purity of 99Tcm-Q12 should be confirmed to prevent interference by liver uptake.

Cardiac effects within 3 months of BEAC high-dose therapy in non-Hodgkin's lymphoma patients undergoing autologous stem cell transplantation.

OBJECTIVES: Limited data are available on the cardiac effects of high-dose cyclophosphamide (CY) in patients with non-Hodgkin's lymphoma (NHL). We prospectively assessed the cardiac effects of high-dose CY in 30 adult NHL patients receiving CY 6 g/m(2) as part of BEAC high-dose therapy (HDT). METHODS: Radionuclide ventriculography (RVG) and plasma natriuretic peptide (NT-proANP, NT-proBNP) measurements were performed simultaneously prior to BEAC at baseline (d - 7), 12 days (d + 12) and 3 months (m + 3) after stem cell infusion (D0). In addition to these time points, natriuretic peptides were measured 2 days before (d - 2) and 1 week (d + 7) after stem cell infusion. RESULTS: Left ventricular ejection fraction (LVEF) decreased from d - 7 (53% +/- 2%) to d + 12 (49% +/- 2%, P = 0.009). However, no significant change in cardiac diastolic function was observed. The LVEF returned towards baseline by m + 3. Plasma NT-proANP and NT-proBNP increased significantly from baseline (445 +/- 65 pmol/L and 129 +/- 33 pmol/L) to d - 2 (1,127 +/- 142 pmol/L, P < 0.001 and 624 +/- 148 pmol/L, P < 0.001, respectively). Thereafter, they started to decrease, but on d + 7 NT-proANP (404 +/- 157 pmol/L, P = 0.048) and NT-proBNP (648 +/- 125 pmol/L, P = 0.015) were still significantly higher than at baseline. On d + 12 and m + 3 they no longer differed from baseline. CONCLUSIONS: Our findings suggest that high-dose CY results in acute, subclinical systolic dysfunction in NHL patients previously treated with anthracyclines. Natriuretic peptides seem to be more sensitive than LVEF to reflect this transient cardiac effect. Serial measurements of natriuretic peptides might be a useful tool to assess cardiac effects of high-dose CY.

Baroreflex sensitivity in men with recent myocardial infarction; impact of age.

We investigated the effect of age on baroreflex sensitivity (BRS) in 39 male patients, who had survived their first myocardial infarction (MI) and in 15 age-matched controls. BRS was inversely related to age in both MI patients (r = -0.632, P < 0.0001) and controls (r = -0.706, P < 0.0001). The relationship between BRS and age, however, was significantly different in MI patients as compared with healthy controls: BRS was markedly higher and the BRS-age regression slope was significantly steeper in controls than in MI patients. As a consequence, the decrease in BRS caused by MI (delta BRS = age-specific expected BRS--measured BRS) was related inversely to age (r = -0.66, P < 0.05) i.e. delta BRS was greatest among young MI patients. However, the relative BRS (BRS% = measured BRS divided by the age-specific expected BRS) did not correlate with age. The average BRS% of MI patients was 37% lower than that of controls. MI size and left ventricular (LV) systolic function did not correlate with BRS. BRS correlated with variables related to cardiac diastolic function (peak late LV filling rate r = -0.43, P < 0.05), exercise capacity (r = 0.31, P < 0.05) and the extent of ST-depression during exercise (r = -0.40, P < 0.05), but all these correlations lost their significance after the adjustment for age. In conclusion, age is a factor that should be taken into consideration when evaluating the mechanisms of BRS impairment associated with different diseases.(ABSTRACT TRUNCATED AT 250 WORDS)

Evaluation of myocardial viability with technetium-99m hexakis-2-methoxyisobutyl isonitrile and iodine-123 phenylpentadecanoic acid and single photon emission tomography.

The detection of viable myocardium in infarcted regions, i.e. hibernating myocardium, is a major goal in clinical cardiology today. We applied combined planar and single photon emission tomography (SPET) to the non-invasive estimation of the left ventricular ejection fraction (LVEF), myocardial blood flow and free fatty acid uptake in the heart. Of the 31 patients with coronary artery disease, 25 (81%) had had a previous myocardial infarction. All patients had at least one persistent perfusion defect on the stress-rest technetium-99m hexakis-2-methoxyisobutyl isonitrile (Sestamibi) study, and the results revealed 57/124 (46%) persistent perfusion defects. As a part of the perfusion study, the LVEF was measured at rest using the first-pass 99mTc-Sestamibi injection, and the mean LVEF was 47% +/- 9% (mean +/- 1 standard deviation). Iodine-123 phenylpentadecanoic acid (123I-pPPA) imaging at rest was performed within 2 weeks from the perfusion study. Then 6-mm transaxial, sagittal and coronal slices of the perfusion and 123I-pPPA studies were reconstructed. The bull's eye displays of the coronal slices were visually surveyed and divided into 4 quadrants: anterior, lateral, posterior and septal. The following image score was used: 0 = fixed defect, 1 = partial uptake and 2 = normal uptake. Moreover an index of metabolic reserve (MR) was calculated by dividing the bull's eye of the 123I-pPPA study by the bull's eye of resting 99mTc-Sestamibi, and its maximum value was normalized to 100%.(ABSTRACT TRUNCATED AT 250 WORDS)

Heart rate variability and its determinants in patients with severe or mild essential hypertension.

How cardiac autonomic nervous control is related to the severity of essential hypertension in patients receiving long-term antihypertensive therapy is not well known. The aim of this study was to examine heart rate variability (HRV), a non-invasive measure of cardiac autonomic function, in patients with long-term and medically treated mild and severe essential hypertension and healthy control subjects, and to assess the clinical determinants of HRV in these patients. Thirty-four patients with severe essential hypertension (SEHT) and 29 with mild essential hypertension (MEHT) as well as healthy age- and sex-matched control subjects were studied. HRV was assessed from 10 min ECG-recordings during paced (0.2 Hz) breathing at rest and expressed as time and frequency domain measures. In the SEHT group time (SDNN, RMSSD) and frequency domain measures (total power, low-frequency (LF) power and high-frequency (HF) power of HRV in absolute units, and LF and HF power of HRV in normalized units) of HRV were significantly lower when compared with those of the control group. The MEHT and control groups did not differ from each other with respect to time or frequency domain measures of HRV. Comparison between the hypertensive groups showed that SDNN, total power, LF power and HF power were lower in the SEHT group compared with the MEHT group (P<0.05 for all). Among hypertensive patients RR-interval, age, gender, systolic finger blood pressure and diastolic office blood pressure as well as 24-h blood pressure were significant determinants of HRV. In conclusion, we found that the severity of chronic essential hypertension seems to be related to the severity of impairment of cardiac autonomic control.

Good exercise capacity at hospital discharge predicts recovery of baroreflex sensitivity after myocardial infarction.

Myocardial infarction results in depressed baroreflex sensitivity, which has been shown to be associated with increased risk of ventricular arrhythmias and sudden death. We measured baroreflex sensitivity in 37 patients with acute myocardial infarction before hospital discharge and 3 months after the infarction to find out whether the baroreflex sensitivity recovers during that period. In addition, baroreflex sensitivity was assessed in 15 healthy controls. Baroreflex sensitivity was assessed from the regression line relating the change in R-R interval to the change in systolic blood pressure following an intravenous bolus injection of phenylephrine. There was a wide inter-individual variation in the change of baroreflex sensitivity (delta baroreflex sensitivity) in infarction patients, but the average baroreflex sensitivity showed no significant change during the 3-month follow-up (10.2 + 5.6 to 11.8 +/- 7.5 ms.mmHg-1, ns) and remained lower than the baroreflex sensitivity of the controls (16.4 +/- 9.7 ms.mmHg-1, P < 0.05). delta Baroreflex sensitivity correlated significantly with exercise capacity measured before hospital discharge. When the patients were divided into tertiles according to the delta baroreflex sensitivity (-3.3 +/- 1.5 ms.mmHg-1 in the lowest tertile, 1.0 +/- 1.0 ms.mmHg-1 in the middle tertile and 7.5 +/- 4.0 ms.mmHg-1 in the highest tertile) the exercise capacity was found to increase from the lowest to the highest tertile (exercise time 357 +/- 115 s, 418 +/- 126 s and 461 +/- 141 s, respectively; P < 0.05 lowest vs highest tertile). Patients with a low exercise tolerance (exercise time < 360 s) showed a significantly smaller delta baroreflex sensitivity than patients with a good exercise tolerance (exercise time > or = 480 s) (-0.5 +/- 4.4 vs 5.3 +/- 5.4 ms.mmHg-1, P < 0.05), respectively. delta Baroreflex sensitivity was not related to the location or type of infarction, thrombolytic therapy, presence of angina pectoris or left ventricular function at the time of discharge. In conclusion, exercise capacity assessed before hospital discharge seems to be a predictor of baroreflex sensitivity recovery in patients with a recent myocardial infarction.

Valsalva manoeuvre in the assessment of baroreflex sensitivity in patients with coronary artery disease.

The overshoot rise in arterial pressure after release of Valsalva strain is a natural challenge for baroreflex regulation of heart rate. To assess the feasibility of the Valsalva manoeuvre in the determination of baroreflex sensitivity (BRS), we measured the slope of the linear relationship between the length of the RR interval and preceding systolic blood pressure value during the overshoot phase after the strain and compared this index of BRS to a standard phenylephrine test in 64 subjects, of whom 58 had coronary artery disease. The BRS slopes obtained with the Valsalva manoeuvre showed a good linear correlation with the phenylephrine test (r = 0.77 in the 27 patients with two Valsalva and phenylephrine tests and r = 0.56 in the whole cohort). The correlation coefficients of the BRS slopes were better than in the phenylephrine test (r = 0.89 vs r = 0.85, P < 0.05). The rise in systolic blood pressure in the slope calculation area was higher than with phenylephrine (41 +/- 18 vs 30 +/- 10 mmHg, P < 0.01). The reproducibility of BRS slopes in successive tests was comparable with both methods. These results suggest that non-invasive assessment of BRS using Valsalva strain to induce blood pressure rise is possible in patients with coronary artery disease.

The effect of a very low-calorie diet-induced weight loss on the severity of obstructive sleep apnoea and autonomic nervous function in obese patients with obstructive sleep apnoea syndrome.

The aim of this study was to examine the effect of a very low-calorie diet (VLCD)-induced weight loss on the severity of obstructive sleep apnoea (OSA), blood pressure and cardiac autonomic regulation in obese patients with obstructive sleep apnoea syndrome (OSAS). A total of 15 overweight patients (14 men and one woman, body weight 114 +/- 20 kg, age 52 +/- 9 years, range 39-67 years) with OSAS were studied prospectively. They were advised to follow a 2.51-3.35 MJ (600-800 kcal) diet daily for a 3-month period. In the beginning of the study, the patients underwent nocturnal sleep studies, autonomic function tests and 24-h electrocardiograph (ECG) recording. In addition, 15 age-matched, normal-weight subjects were studied. They underwent the Valsalva test, the deep-breathing test and assessment of heart rate variability at rest. The sleep studies and autonomic function tests were repeated after the weight loss period. There was a significant reduction in weight (114 +/- 20 kg to 105 +/- 21 kg, P < 0.001), the weight loss being 9.2 +/- 4.0 kg (range 2.3-19.5 kg). This was associated with a significant improvement in the oxygen desaturation index (ODI4) during sleep (31 +/- 20-19 +/- 18, P < 0.001). Before the weight loss the OSAS patients had significantly higher blood pressure (150 +/- 18 vs. 134 +/- 20, P < 0.05, for systolic blood pressure, 98 +/- 10 vs. 85 +/- 13, P < 0.05, for diastolic blood pressure) and heart rate (67 +/- 10 beats min-1 vs. 60 +/- 13, P < 0.05) at rest than the control group. They had also lower baroreflex sensitivity (4.7 +/- 2.8 ms mmHg-1 vs. 10.8 +/- 7.1 ms mmHg-1, P < 0.01). During the weight reduction, the blood pressure declined significantly, and the baroreflex sensitivity increased by 49%. In conclusion, our experience shows that weight loss with VLCD is an effective treatment for OSAS. Weight loss improved significantly sleep apnoea and had favourable effects on blood pressure and baroreflex sensitivity that may have prognostic implications.