Circulating annexin A5 predicts mortality in patients with heart failure.

BACKGROUND: Natriuretic peptides are currently used to predict mortality in patients with heart failure (HF). However, novel independent biomarkers are needed to improve risk stratification in these patients. We hypothesized that annexin A5 (anxA5) would be highly expressed by organs which are generally affected by HF and that circulating anxA5 levels would predict mortality in HF patients. METHODS: We prospectively determined the diagnostic value of anxA5, N-terminal pro-B-type natriuretic peptide (NT-proBNP), C-reactive protein (CRP) and estimated glomerular filtration rate (eGFR) to predict mortality in 180 HF patients during a median follow-up of 3.6 years. Studies were conducted with anxA5(-/-) mice to investigate the underlying mechanisms. RESULTS: AnxA5 levels were significantly elevated in HF patients compared to healthy control subjects. Cox regression analysis demonstrated that anxA5, NT-proBNP and eGFR all predict mortality independently. AnxA5 significantly improved the diagnostic efficiency of NT-proBNP alone (improvement of c-statistic from 0.662 to 0.705, P < 0.001) and also combined with eGFR and CRP (improvement of c-statistic from 0.675 to 0.738, P < 0.001) to predict mortality in the Cox regression model. Receiver operating characteristic curve analysis showed that anxA5 predicted 3-year survival (area under curve 0.708) with an optimal cut-off value of 2.24 ng mL(-1) . Using anxA5(-/-) mice, we demonstrated that anxA5 is highly expressed in organs that are often affected by HF including lung, kidney, liver and spleen. Lysis of these organs in vitro resulted in a marked and significant increase in anxA5 concentrations. CONCLUSION: AnxA5 improves the diagnostic efficiency of conventional biomarkers to predict mortality in HF patients. Whereas natriuretic peptides originate from the myocardium, high circulating anxA5 levels in patients with HF are likely to reflect peripheral organ damage secondary to HF.

Microbiota-dependent metabolite trimethylamine-N-oxide is associated with disease severity and survival of patients with chronic heart failure.

OBJECTIVES: Recent metabolomic, experimental and clinical studies have demonstrated that trimethylamine-N-oxide (TMAO), a microbiota-dependent metabolite from dietary phosphatidylcholine and carnitine, is a strong predictor of coronary artery disease (CAD). This finding suggests a link between the gut microbiota and atherosclerosis. The potential impact of TMAO in chronic heart failure (HF) is unknown. We hypothesized that TMAO levels would provide prognostic information about adverse outcomes in chronic HF. DESIGN: Prospective, observational study including 155 consecutive patients with chronic HF. In addition, 100 patients with stable CAD without HF and 33 matched healthy individuals were included as controls. Plasma levels of TMAO and its precursors choline and betaine were measured, and associations with symptoms, aetiology and transplant-free survival in the patients with HF were explored. RESULTS: Plasma levels of TMAO (P = 0.01), choline (P < 0.001) and betaine (P < 0.001) were elevated in patients with chronic HF compared to control subjects, with the highest levels in patients with New York Heart Association (NYHA) classes III and IV. Furthermore, TMAO levels were highest in individuals with ischaemic HF, followed by those with stable CAD and nonischaemic HF. TMAO, but not choline or betaine, was associated with reduced transplant-free survival: approximately 50% of patients in the upper tertile of TMAO levels died or received a heart transplant during 5.2 years of follow-up (unadjusted Cox-regression: hazard ratio 2.24, 95% confidence interval 1.28-3.92, P = 0.005). CONCLUSIONS: TMAO levels were elevated in patients with HF and associated with NYHA class, ischaemic aetiology and adverse outcomes. Future studies should focus on gut microbiota, dietary composition and intestinal dysfunction in relation to TMAO levels and clinical outcome in HF.

The cardiokine secreted Frizzled-related protein 3, a modulator of Wnt signalling, in clinical and experimental heart failure.

OBJECTIVES: Experimental studies have shown involvement of Wnt signalling in heart failure (HF). We hypothesized that secreted frizzled-related protein 3 (sFRP3), a modulator of Wnt signalling, is related to the progression of HF. DESIGN: Circulating sFRP3 was measured in 153 HF patients and compared with 25 healthy controls. The association of sFRP3 with mortality was evaluated in 1202 patients (GISSI-HF trial). sFRP3 mRNA expression was assessed in failing human and murine left ventricles (LV), and cellular localization was determined after fractioning of myocardial tissue. In vitro studies were carried out in cardiac fibroblasts subjected to cyclic mechanical stretch. RESULTS: (i) Heart failure patients had significantly raised serum sFRP3 levels compared with controls, (ii) during a median follow-up of 47 months, 315 patients died in the GISSI-HF substudy. In univariable Cox regression, tertiles of baseline sFRP3 concentration were significantly associated with all-cause and cardiovascular mortality. After adjustment for demographic and clinical variables, but not for CRP and NT-proBNP, the associations with mortality remained significant for the third tertile (all-cause, HR 1.45, P = 0.011; cardiovascular, HR 1.66, P = 0.003), (iii) sFRP3 mRNA expression was increased in failing human LV, with a decline following LV assist device therapy. LV from post-MI mice showed an increased sFRP3 mRNA level, particularly in cardiac fibroblasts, and (iv) mechanical stretch enhanced sFRP3 expression and release in myocardial fibroblasts. CONCLUSION: There is an association between increased sFRP3 expression and adverse outcome in HF, suggesting that the failing myocardium itself contributes to an increase in circulating sFRP3.

Altered maternal left ventricular contractility and function during normal pregnancy.

OBJECTIVES: To evaluate maternal left ventricular (LV) systolic and diastolic function during normal pregnancy by non-invasive measures of LV contractility incorporating loading conditions. METHODS: Sixty-five women were examined using echocardiography, including tissue Doppler and two-dimensional speckle tracking, and subclavian artery pulse trace recordings at gestational weeks 14-16, 22-24 and 36, and at 6 months postpartum. RESULTS: The mean ± SD age of the women was 32.0 ± 4.6 years. Cardiac output and LV end-diastolic volume were on average 20% and 23% higher, respectively, during pregnancy, compared to that at 6 months postpartum (both, P < 0.01). LV ejection fraction, global peak systolic strain and rate-corrected LV velocity of circumferential fiber shortening (Vcfc) were 11%, 6% and 6% lower, respectively, at 36 weeks' gestation compared to at 6 months postpartum (all, P < 0.01). Afterload, measured as LV end-systolic wall stress (ESWS) increased by 10% between 14-16 and 36 weeks' gestation (P < 0.01). Analysis of the relationship between Vcfc and ESWS revealed that LV contractility was lower during pregnancy than at 6 months postpartum. Changes in diastolic function were demonstrated by 11% lower mitral early diastolic (E) wave velocity, 8% lower tissue Doppler early diastolic velocity (e') and 13% higher left atrial area (all P < 0.01) during pregnancy. Tissue Doppler E/e' remained unaltered (P = 0.78). CONCLUSIONS: During normal pregnancy, LV contractility is lower than it is at 6 months postpartum. This is associated with increased LV and left atrial area, whereas filling pressures are unchanged. These findings suggest that pregnancy exerts a larger load on the cardiovascular system than previously assumed.

High-intensity interval training improves peak oxygen uptake and muscular exercise capacity in heart transplant recipients.

Heart transplant (HTx) recipients usually have reduced exercise capacity with reported VO(2peak) levels of 50-70% predicted value. Our hypothesis was that high-intensity interval training (HIIT) is an applicable and safe form of exercise in HTx recipients and that it would markedly improve VO(2peak.) Secondarily, we wanted to evaluate central and peripheral mechanisms behind a potential VO(2peak) increase. Forty-eight clinically stable HTx recipients >18 years old and 1-8 years after HTx underwent maximal exercise testing on a treadmill and were randomized to either exercise group (a 1-year HIIT-program) or control group (usual care). The mean ± SD age was 51 ± 16 years, 71% were male and time from HTx was 4.1 ± 2.2 years. The mean VO(2peak) difference between groups at follow-up was 3.6 [2.0, 5.2] mL/kg/min (p < 0.001). The exercise group had 89.0 ± 17.5% of predicted VO(2peak) versus 82.5 ± 20.0 in the control group (p < 0.001). There were no changes in cardiac function measured by echocardiography. We have demonstrated that a long-term, partly supervised and community-based HIIT-program is an applicable, effective and safe way to improve VO(2peak) , muscular exercise capacity and general health in HTx recipients. The results indicate that HIIT should be more frequently used among stable HTx recipients in the future.

Osteoprotegerin levels predict mortality in patients with symptomatic aortic stenosis.

OBJECTIVES: To examine the prognostic value of osteoprotegerin (OPG) levels in relation to all-cause mortality in patients with symptomatic severe aortic stenosis (AS). DESIGN: We measured plasma OPG levels in 136 patients with symptomatic severe AS and investigated associations with transvalvular gradients, valve area, valve calcification (using ultrasonic backscatter analysis as an estimate) and measures of heart failure. Then, we assessed the prognostic value of elevated plasma OPG in determining all-cause mortality (n = 29) in these patients. RESULTS: Elevated OPG was poorly correlated with the degree of AS but was associated with increased backscatter measurements and impaired cardiac function. Furthermore, OPG was associated with all-cause mortality in patients with symptomatic AS, even after adjustment for conventional risk markers. The strongest association was obtained by using a combination of high levels of both OPG and N-terminal pro-brain natriuretic peptide (NT-proBNP), suggesting that these markers may reflect distinct pathways in the development and progression of AS. CONCLUSION: The level of circulating OPG is significantly associated with all-cause mortality alone and in combination with NT-proBNP in patients with severe symptomatic AS.

Undercarboxylated matrix Gla protein is associated with indices of heart failure and mortality in symptomatic aortic stenosis.

OBJECTIVE: Matrix Gla protein (MGP) is a calcification inhibitor and alterations in circulating MGP have been observed in different populations characterized by vascular calcification. We hypothesized that patients with calcific valvular aortic stenosis (AS) would have dysregulated circulating MGP levels. DESIGN AND SUBJECTS: We examined plasma levels of nonphosphorylated carboxylated and undercarboxylated MGP (dp-cMGP and dp-ucMGP, respectively) in 147 patients with symptomatic severe AS and in matched healthy controls. MAIN OUTCOME MEASURES: We further investigated the relationship between MGP levels and aortic pressure gradients and valve area by echocardiography and measures of heart failure. Finally, we assessed the prognostic value of elevated plasma dp-ucMGP level in relation to all-cause mortality in patients with AS. RESULTS: We found markedly enhanced plasma levels of dp-cMGP and in particular of dp-ucMGP in patients with symptomatic AS. Although only weak correlations were found with the degree of AS, circulating dp-ucMGP was associated with cardiac function and long-term mortality in multivariate analysis. CONCLUSIONS: A dysregulated MGP system may have a role in the development of left ventricular dysfunction in patients with symptomatic AS.

Prevalence, risk factors, and type of sleep apnea in patients with paroxysmal atrial fibrillation.

BACKGROUND: Recent studies have suggested an association between sleep apnea (SA) and atrial fibrillation (AF). We aimed to study the prevalence, characteristics, risk factors and type of sleep apnea (SA) in ablation candidates with paroxysmal AF. METHODS/RESULTS: We prospectively studied 579 patients with paroxysmal AF, including 157 women (27.1%) and 422 men (72.9%). Mean age was 59.9 ± 9.6 years and mean body mass index (BMI) 28.5 ± 4.5 kg/m2. SA was diagnosed using polygraphy for two nights at home. The Epworth Sleepiness Scale (ESS), STOP-Bang Questionnaire, and Berlin Questionnaire (BQ) assessed the degree of SA symptoms. A total of 479 (82.7%) patients had an apnea-hypopnea index (AHI) ≥ 5, whereas moderate-severe SA (AHI ≥ 15) was diagnosed in 244 patients (42.1%). The type of SA was predominantly obstructive, with a median AHI of 12.1 (6.7-20.6) (range 0.4-85.8). The median central apnea index was 0.3 (0.1-0.7). AHI increased with age, BMI, waist and neck circumference, body and visceral fat. Using the Atrial Fibrillation Severity Scale and the SF-36, patients with more severe SA had a higher AF burden, severity and symptom score and a lower Physical-Component Summary score. Age, male gender, BMI, duration of AF, and habitual snoring were independent risk factors in multivariate analysis (AHI ≥ 15). We found no association between ESS and AHI (R2 = 0.003, p = 0.367). CONCLUSIONS: In our AF population, SA was highly prevalent and predominantly obstructive. The high prevalence of SA detected in this study may indicate that SA is under-recognized in patients with AF. None of the screening questionnaires predicted SA reliably.

Regional myocardial systolic function during acute myocardial ischemia assessed by strain Doppler echocardiography.

OBJECTIVES: We sought to evaluate if echocardiographic strain measurements could detect acute myocardial ischemia, and to compare this new method with myocardial velocity measurements and wall motion score index. BACKGROUND: Tissue Doppler echocardiography (TDE) is a promising method for assessing regional myocardial function. However, myocardial velocities measured by tissue Doppler echocardiography (TDE) vary throughout the left ventricle (LV) because of tethering effects from adjacent tissue. Strain Doppler echocardiography (SDE) is a new tool for measuring regional myocardial deformation excluding the effect of adjacent myocardial tissue. METHODS: Seventeen patients undergoing angioplasty of the left anterior descending coronary artery (LAD) were studied. Left ventricular longitudinal wall motion was assessed by TDE and SDE from the apical four-chamber view before, during and after angioplasty from multiple myocardial segments simultaneously. RESULTS: Systolic strain values were uniformly distributed in the different nonischemic LV segments, whereas systolic velocities decreased from basis to apex. During LAD occlusion, strain measurement showed expansion in the apical septal segment in 16 of 17 patients (7.5 +/- 6.5% vs. -17.7 +/- 7.2%, p < 0.001) and reduced compression in the mid-septal segment (p < 0.05) compared with baseline. Segments not supplied by LAD remained unchanged. Tissue Doppler echocardiography showed reduced velocities in all septal segments (p < 0.05) during angioplasty even though LAD does not supply the basal septal segment. Negative systolic velocities were present in 11 of 17 patients. Wall motion score index increased during ischemia (1.3 +/- 0.4, p < 0.05). CONCLUSIONS: The new SDE approach might be a more accurate marker than TDE for detecting systolic regional myocardial dysfunction induced by LAD occlusion.

Digital dipyridamole stress echocardiography in silent ischemia after coronary artery bypass grafting and/or after healing of acute myocardial infarction.

This study evaluates dipyridamole stress echocardiography in silent ischemia. Fourteen patients with previous coronary artery bypass grafting (group A) and 16 patients with healed myocardial infarction (group B) were studied. All had > or = 1 mm ST depression without chest pain during bicycle exercise testing. Left ventricular wall motion was analyzed using a computerized display of digital systolic cineloops with a high frame rate. Test results were compared with coronary angiography. Dipyridamole echocardiography accurately identified patients with significant coronary artery stenosis in both groups (3 of 4 in group A, 11 of 14 in group B). Retrograde flow to the occluded native artery was associated with positive results on dipyridamole testing in 6 of 7 patients in group A and all 3 in group B. Sensitivity, specificity and diagnostic accuracy for detecting significant coronary stenosis or occlusions with retrograde flow was 78, 100 and 83%, respectively. Patients with angiographic multivessel disease had a significantly larger increase in wall motion score index during dipyridamole stress than patients with 0- or 1-vessel disease, 0.18 +/- 0.11 versus 0.05 +/- 0.18 (p < 0.05). Two patients developed symptomatic bradycardia and hypotension during dipyridamole infusion. It is concluded that dipyridamole echocardiography accurately identifies myocardial regions with restricted coronary flow. Stress echocardiography is a valuable tool for assessing coronary flow in silent ischemia.

Noninvasive computerized assessment of left ventricular performance and systemic hemodynamics by study of aortic root pressure and flow estimates in healthy men, and men with acute and healed myocardial infarction.

Aortic root pressure and flow data can be used to assess left ventricular (LV) performance and properties of the systemic arterial tree. The calibrated subclavian arterial pulse trace was combined with echocardiographic imaging and Doppler velocity recordings to obtain noninvasive estimates of aortic root pressure and flow in 8 healthy subjects (group A), 12 patients with recent myocardial infarction (group B), and 8 with healed myocardial infarction and a dilated left ventricle (group C). The pressure and flow data were transferred to a computer and processed in specially designed software, including a new procedure for estimation of 3-element windkessel model parameters. There were no significant group differences for either aortic root pressure estimates or heart rate. In groups B and C, stroke and cardiac indexes were lower and total peripheral resistance higher than in group A. There were no group differences in the model estimates of total arterial compliance, whereas the characteristic impedance was greater in group C than in A, indicating a less compliant aorta in C. Both LV total and steady power were less in groups B and C than in A, whereas no group difference was found for percent oscillatory power. The reproducibility for recording was good for the aortic root pressure estimates, and lower for the derived parameters (stroke and cardiac indexes, windkessel model parameters and LV power), whereas that for interpretation was generally good. This method provides a unique noninvasive access to important parameters of LV function and the systemic circulation.

Hemodynamics in white coat hypertension compared to ambulatory hypertension and normotension.

Hemodynamic alterations associated with the blood pressure response in subjects with white coat hypertension may provide insight into the pathophysiologic mechanisms of this condition. Systemic arterial hemodynamics were investigated with a recently validated method based on noninvasive estimates of aortic root pressure and flow in 28 subjects with white coat hypertension (diastolic pressure > or = 90 mm Hg measured by the general practitioner [GP arterial pressure] and ambulatory daytime pressures < 140/90 mm Hg), in 23 subjects with previously untreated, ambulatory hypertension (GP diastolic pressure > or = 90 and < 115 mm Hg and ambulatory daytime diastolic pressure > or = 90 mm Hg), and in 32 normotensive subjects. The groups did not differ significantly concerning age, gender, body surface area, heart rate, stroke index and cardiac index, but total peripheral resistance index was increased and total arterial compliance reduced in the white coat group and the hypertensive group compared to the normotensive group. The subjects in the white coat group with a systolic arterial pressure during echocardiography that was > 5 mm Hg higher than the ambulatory daytime systolic pressure (n = 19) had increased cardiac index, increased total peripheral resistance, and decreased total arterial compliance compared to the normotensive group. The subjects in this group with a hemodynamic pattern characterized by a high ratio of cardiac index/peripheral vascular resistance were significantly younger than the subjects with the opposite pattern. Thus, the blood pressure increase in subjects with white coat hypertension is associated with increased cardiac output, increased peripheral vascular resistance, and reduced total arterial compliance, but the hemodynamic pattern may be influenced by age.

Calcitonin gene-related peptide (human alpha-CGRP) counteracts vasoconstriction in human subarachnoid haemorrhage.

Calcitonin gene-related peptide (CGRP) is a neuropeptide co-stored with tachykinins (substance P, neurokinin A) in cerebrovascular sensory fibers in the trigeminal ganglion. Preceding studies on subarachnoid hemorrhage (SAH) revealed that an enhanced release of CGRP resulted in the selective loss of perivascular CGRP. Therefore, the present study was designed to evaluate the effects of intravenous administration of human alpha-CGRP on cerebral vasoconstriction in the postoperative course after SAH in 5 patients (8 infusions). Cerebral vasoconstriction was evaluated with transcranial Doppler sonography. The increase in the relationship between middle cerebral artery (MCA) velocity and internal carotid artery (ICA) velocity (the hemodynamic index) was used as an indicator of vasoconstriction and compared to the contralateral side. A significant reduction was found in the hemodynamic index during the CGRP infusion (4.3 +/- 0.5, P < 0.05) as to compared to before infusion (6.2 +/- 0.5). There was no measurable change in the hemodynamic index on the contralateral side. No significant change was observed in pulsatility index, blood pressure or consciousness during the peptide infusion. A significant increase in heart rate was observed during the infusion as compared to before and after infusion (90 +/- 4 vs. 76 +/- 5). Cardiac ultrasound data indicated a mean cardiac output increase of 1.9 liter/min, and a mean decrease in total peripheral resistance of 538 dynes s/cm5. The results obtained show that infusion of human alpha-CGRP may induce normalisation of cerebrovascular tone in SAH.

A new method for echocardiographic computerized three-dimensional reconstruction of left ventricular endocardial surface: in vitro accuracy and clinical repeatability of volumes.

This study evaluates the in vitro accuracy and clinical repeatability of volumes derived by a new algorithm for three-dimensional reconstruction of cavity surfaces based on echocardiographic apical images obtained by probe rotation. The accuracy of the method was tested in latex phantoms (true volumes, 32 to 349 cm3) with (n = 9) or without (n = 9) rotational symmetry around the midcavitary long axis. Repeatability of left ventricular volumes was assessed in subjects without (n = 5) or with (n = 10) myocardial disease. Estimated phantom volumes obtained from four (three) imaging planes were close to true volumes with a mean difference +/- SD of 0 +/- 2 (2 +/- 3) cm3 in symmetric and 1 +/- 3 (4 +/- 4) cm3 in asymmetric objects. Biplane and single-plane volume estimates were less accurate. Interobserver and intraobserver repeatability of three-dimensional left ventricular volumes was good for analysis (coefficients of variation: 3.5% to 6.2%) and was lower for recording (coefficients of variation: 7.4% to 10.9%). Hence the present algorithm reproduces volumes of symmetric and deformed in vitro objects accurately over a wide range of size and shape, and it produces repeatable left ventricular volumes in the clinical situation.

Reversal of intraventricular flow propagation during isovolumic relaxation: A marker of anterior wall dysfunction.

BACKGROUND: Myocardial infarction induces left ventricular (LV) wall motion abnormalities during isovolumic relaxation (IVR) and may potentially alter intraventricular flow during this period. This study evaluated whether 2-dimensional color Doppler measurements of intraventricular flow during IVR were able to identify LV dysfunction caused by coronary artery disease. METHODS: Patients with single-vessel coronary artery disease and posterior wall infarction (21 patients) or anterior wall infarction (27 patients) were included. Eighteen healthy persons served as a control group. LV function was examined by 2-dimensional echocardiography, 2-dimensional color Doppler, and pulsed Doppler techniques. RESULTS: All normal persons (23.6 +/- 10.9 cm/s) and patients with posterior infarction (19.6 +/- 9.3 cm/s) had flow propagation towards LV apex during IVR. Patients with anterior wall infarction had reversed flow direction (-12.2 +/- 8.7 cm/s, P <.001). The echocardiographic wall motion score index of the 4 apical segments correlated well with flow velocities (r = -0.78, P <.001). CONCLUSION: Reversed flow propagation during IVR may become a sensitive clinical marker of regional ischemia.

Sublingual nitroglycerin delays arterial wave reflections despite increased aortic "stiffness" in patients with hypertension: a Doppler echocardiography study.

Venodilatation with consequent reduction in left ventricular filling and end-diastolic wall stress is an important mechanism for the beneficial effects of nitroglycerin in ischemic heart disease and in left ventricular failure. The effects of sublingual nitroglycerin on arterial pulsatile hemodynamics are less well defined. Doppler echocardiography and the calibrated subclavian artery pulse tracing were used to assess hemodynamics in subjects with sustained arterial hypertension (n = 25) before and 5 to 10 minutes after sublingual deposition of 0.5 mg glyceryl trinitrate. Aortic characteristic impedance was calculated by averaging the modulus of the input impedance (ratio of pressure to flow) at high frequencies and by calculating the ratio of pressure and flow increments during upstroke. The pressure wave was split into forward and backward components, and the reflection coefficient (the ratio of backward to forward pressures) was calculated. Parameters of the arterial bed were estimated by using 2- and 3-element Windkessel models. Nitroglycerin delayed the return of arterial wave reflections by 17% (P =.02) and increased aortic characteristic impedance by 20% (P =. 01), but it did not influence total arterial compliance. Mean arterial pressure decreased 7% (P =.0001), but pulse pressure did not change. Stroke volume and the acceleration time of aortic root flow decreased by 13% (P =.0001) and 8% (P =.01), respectively. Cardiac output decreased 7% (P =.01), despite an increase in heart rate of 10% (P =.0001). Peripheral resistance tended to decrease (4%, P =.06). Thus, in subjects with sustained hypertension, sublingual nitroglycerin dilates peripheral, predominantly muscular arteries with a subsequent delayed return of reflected pressure waves. Reflex activation of the sympathetic nervous system with consequent increased acceleration of left ventricular ejection seems to counteract the effect of reduced mean arterial pressure (distending pressure) with respect to the "stiffness" of the aorta.

Acute regional myocardial ischemia identified by 2-dimensional multiregion tissue Doppler imaging technique.

BACKGROUND AND OBJECTIVE: Tissue Doppler echocardiography (TDE) is a promising method for the assessment of regional myocardial function, but pulsed TDE does not provide quantitative data from multiple regions simultaneously. This feature is important for the objective assessment of regional differences in myocardial function. In the present study, we investigated a new off-line TDE method that provides quantitative pulsed velocity data from an unlimited number of regions selected within a 2-dimensional (2D) image. The goal of the study was to determine the ability of this new approach to quantify regional myocardial function during acute myocardial ischemia induced by balloon angioplasty. METHODS: Twenty-two patients undergoing angioplasty of the left anterior descending coronary artery (LAD) were studied. Left ventricular longitudinal wall motion was assessed by 2D TDE from the apical 4-chamber view before, during, and after angioplasty. Images were sampled at a rate of 69 +/- 15 frames/s, and the off-line analysis allowed simultaneous measurement of velocities in multiple myocardial segments. RESULTS: There were 3 major alterations in the systolic velocity pattern during LAD occlusion. Peak early systolic velocities along the apical septum were significantly reduced during LAD occlusion (2.8 +/- 1.2 cm/s to 0.6 +/- 1.7 cm/s, P <.001). Myocardial velocities in mid systole suggested paradoxical wall motion (1.0 +/- 1.2 cm/s to -0.8 +/- 0.9 cm/s, P <.001). When comparing the ischemic regions of the left ventricle with the nonischemic regions, each patient demonstrated lower myocardial systolic velocities in the ischemic region. Furthermore, during early diastole, the wall motion of the ischemic segments showed a postsystolic contraction pattern with velocities changing from -0.9 +/- 1.0 cm/s to 1.9 +/- 1.3 cm/s (P <.001). CONCLUSION: This new 2D TDE approach is able to quantify detailed myocardial velocity profiles from multiple regions simultaneously. Single-beat comparisons of ischemic and nonischemic regions might enhance the sensitivity for diagnosing ischemic heart disease. Reversed systolic wall motion during midsystole and marked positive velocity during early diastole might be new and important markers of myocardial wall ischemia.

Anterior perforations in lumbar discectomies. A report of four cases of vascular complications and a CT study of the prevertebral lumbar anatomy.

Four cases of vascular complications to anterior perforations during discectomy prompted a CT study to measure lumbar disc diameters and to evaluate the prevertebral anatomy. Fifty young adults who had been referred for low-back pain and/or sciatica but had not undergone operation were included. In five additional patients, prone versus supine CT examinations were compared. Six typical configurations of the vascular anatomy could be classified to explain the type of vascular complications occurring at the L3-4 and L4-L5 disc levels. The sagittal diameter of the three lowest lumbar discs varied from 33 to 56 mm, indicating the importance of this parameter as an intraoperative guideline for the spine surgeon. Air-filled intestines were observed anterior to the L5-S1 disc predominantly in the prone position. The possible relationship between this finding and postoperative discitis is discussed.

Long-term results after intracoronary injection of autologous mononuclear bone marrow cells in acute myocardial infarction: the ASTAMI randomised, controlled study.

OBJECTIVE: To investigate long-term safety and efficacy after intracoronary injection of autologous mononuclear bone marrow cells (mBMCs) in acute myocardial infarction (AMI). DESIGN: Randomised, controlled trial. SETTING: Two university hospitals in Oslo, Norway. PATIENTS: Patients from the Autologous Stem cell Transplantation in Acute Myocardial Infarction (ASTAMI) study were re-assessed 3 years after inclusion. INTERVENTIONS: 100 patients with anterior wall ST-elevation myocardial infarction treated with acute percutaneous coronary intervention (PCI) were randomised to receive intracoronary injection of mBMCs (n = 50) or not (n = 50). MAIN OUTCOME MEASURES: Change in left ventricular (LV) ejection fraction (primary). Change in exercise capacity (peak VO(2)) and quality of life (secondary). Infarct size (additional aim), and safety. RESULTS: The rates of adverse clinical events in the groups were low and equal. There were no significant differences between groups in change of global LV systolic function by echocardiography or magnetic resonance imaging (MRI) during the follow-up. On exercise testing, the mBMC-treated patients had larger improvement in exercise time from 2-3 weeks to 3 years (1.5 minutes vs 0.6 minutes, p = 0.05), but the change in peak oxygen consumption did not differ (3.0 ml/kg/min vs 3.1 ml/kg/min, p = 0.75). CONCLUSION: The results indicate that intracoronary mBMC treatment in AMI is safe in the long term. A small improvement in exercise time in the mBMC group was found, but no other effects of treatment could be identified 3 years after cell therapy.

[Chloroquine poisoning]. / Klorokinforgiftning.

Chloroquine poisoning has profound effects, chiefly on contractility and conduction of the heart. No treatment has been proven effective, and most cases of serious poisoning are fatal. We describe one case of chloroquine poisoning and discuss its treatment.