Left atrial appendage occlusion in recurrent ischaemic stroke, a multicentre experience.

BACKGROUND: Oral anticoagulation therapy (OAC) remains the gold standard for ischaemic stroke prevention in patients with non-valvular atrial fibrillation (NVAF) and elevated stroke risk. Percutaneous left atrial appendage occlusion (LAAO) has emerged as a potential alternative for stroke prevention in patients who cannot tolerate OAC. Although no randomized data is available, recurrent stroke in NVAF-patients, while on adequate OAC, is regarded as a treatment failure and therefore is considered as a potential indication for LAAO, based upon expert opinion. METHODS/OBJECTIVES: A multicentre retrospective cohort study evaluating efficacy, safety and mortality of LAAO in NVAF-patients presenting with recurrent ischaemic stroke, after excluding other plausible causes. RESULTS: Fifteen LAAO have been performed in NVAF-patients with recurrent stroke despite ongoing OAC, after exclusion of other plausible causes. Mean age was 78.1 ± 5.8 years, mean CHA2DS2-VASc-score = 6 ± 1.2 and mean HAS-BLED-score = 5 ± 1.2. Successful implantation was achieved in all patients (73% Amplatzer device and 27% Watchman device), without any access-related complications and only one procedure/device-related complication (device embolization) was reported. In all but four patients, OAC was continued at long term after LAAO. No haemorrhagic strokes and only two ischaemic strokes were observed. During follow-up three patients died, all due to non-atrial fibrillation or non-device-related causes. CONCLUSIONS: In NVAF-patients at high risk for stroke presenting with recurrent stroke despite adequate OAC, LAAO may be considered an adjunctive, but not alternative treatment to OAC with high feasibility and safety.Abbreviations: AF: atrial fibrillation; ESC: European Society of Cardiology; INR: international normalized ratio; LAA: left atrial appendage; LAAO: left atrial appendage occlusion; NOAC: non-vitamin K oral anticoagulants; NVAF: non-valvular atrial fibrillation; OAC: oral anticoagulation; RS: recurrent (ischaemic) stroke; SD: standard deviation; TIA: transient ischaemic attack; TOE: transoesophageal echocardiography; TTE: transthoracic echocardiography; VKA: vitamin K antagonists.

Air pollution and ST-elevation myocardial infarction: A case-crossover study of the Belgian STEMI registry 2009-2013.

BACKGROUND: Previous studies have shown that air pollution particulate matter (PM) is associated with an increased risk for myocardial infarction. The effects of air pollution on the risk of ST-elevation myocardial infarction (STEMI), in particular the role of gaseous air pollutants such as NO2 and O3 and the susceptibility of specific populations, are still under debate. METHODS: All patients entered in the Belgian prospective STEMI registry between 2009 and 2013 were included. Based on a validated spatial interpolation model from the Belgian Environment Agency, a national index was used to address the background level of air pollution exposure of Belgian population. A time-stratified and temperature-matched case-crossover analysis of the risk of STEMI was performed. RESULTS: A total of 11,428 STEMI patients were included in the study. Each 10µg/m3 increase in PM10, PM2.5 and NO2 was associated with an increased odds ratio (ORs) of STEMI of 1.026 (CI 95%: 1.005-1.048), 1.028 (CI 95%: 1.003-1.054) and 1.051 (CI 95%: 1.018-1.084), respectively. No effect of O3 was found. STEMI was associated with PM10 exposure in patients ≥75y.o. (OR: 1.046, CI 95%: 1.002-1.092) and with NO2 in patients ≤54y.o. (OR: 1.071, CI 95%: 1.010-1.136). No effect of air pollution on cardiac arrest or in-hospital STEMI mortality was found. CONCLUSION: PM2.5 and NO2 exposures incrementally increase the risk of STEMI. The risk related to PM appears to be greater in the elderly, while younger patients appear to be more susceptible to NO2 exposure.

Role of the ECG in initial acute coronary syndrome triage: primary PCI regardless presence of ST elevation or of non-ST elevation.

The major initial triaging decision in acute coronary syndrome (ACS) is whether or not percutaneous coronary intervention (PCI) is the primary treatment. Current guidelines recommend primary PCI in ST-elevation ACS (STEACS) and initial antithrombotic therapy in non-ST-elevation ACS (NSTEACS). This review probes the question whether this decision can indeed be based on the ECG. Genesis of STE/NSTE ECGs depends on the coronary anatomy, collateral circulation and site of the culprit lesion. Other causes than ischaemia may also result in ST-segment changes. It has been demonstrated that the area at risk cannot reliably be estimated by the magnitude of the ST change, that complete as well as incomplete occlusions can cause STE as well as NSTE ECGs, and that STE and NSTE patterns cannot differentiate between transmural and non-transmural ischaemia. Furthermore, unstable angina can occur with STE and NSTE ECGs. We conclude that the ECG can be used to assist in detecting ischaemia, but that electrocardiographic STE and NSTE patterns are not uniquely related to distinctly different pathophysiological mechanisms. Hence, in ACS, primary PCI might be considered regardless of the nature of the ST deviation, and it should be done with the shortest possible delay, because 'time is muscle'.

In vivo visualization of 111In labeled CD133+ peripheral blood stem cells after intracoronary administration in patients with chronic ischemic heart disease.

AIM: Stem cell homing to injured tissue is necessary for local tissue repair. But homing of stem cells in chronic ischemic heart disease (CIHD) is poorly understood. This study investigated homing of peripheral blood stem cells (PBSC) expressing the CD133 antigen. After intracoronary injection. The cells were (111)In labeled for in vivo visualization. METHODS: PBSC were mobilized with granulocyte-colony stimulating factor and collected by apheresis on d-1. On d0, CD133+ cells were enriched up to a median purity of 89% (range: 79-97%) with an immunomagnetic separation device (CliniMACS, Miltenyi). A fraction of the cells was radiolabeled with [(111)In]oxine in 0.1 M TRIS at pH 7.4 for 45-60 min. Cell viability after labeling was assessed using trypan-blue. The cells were injected at a radioactive concentration of 0.9 MBq/10(6) cells into the target open coronary vessel through a balloon catheter. During balloon inflation [(99m)Tc]sestamibi was injected intravenously to identify the myocardium and the target vascular territory. Eight patients (mean age: 53 years; range: 50-72 years) with stable CIHD and reduced left ventricular function (NYHA class I-II) after acute myocardial infarction (>12 months) were studied. After a first cohort of 3 patients received an injectate of 5-10 x 10(6) cells, our final protocol was applied in 5 patients in whom an average of 34.4 x 10(6) (range: 18.6-49.4) CD133+ cells was injected. Whole body and single photon emission computed tomography (SPECT) scans were acquired at different time points after injection (energy windows set at 140, 171 and 245 keV). Residual activity in the heart was assessed by drawing a region of interest around the heart on the anterior whole body views. RESULTS: Mean labeling efficiency of [111In]oxine labeling was 51.2% and cell viability after labeling averaged 88%. In the 5 patients receiving the higher amount of labeled cells, a clear (111)In-signal was observed in the heart region up to 3 days after administration. Fused [(99m)Tc]sestamibi/(111)In SPECT images demonstrated that the regional distribution of the transplanted cells within the target zone, as delineated by the flow tracer, remained unchanged over time. A biodistribution study in 2 patients showed a residual activity in the heart, liver and spleen of 6.9-8%, 23.1-26.8%, 3.1-3.7%, respectively, after 1-2 h and 2.3-3.2% 23.8-28.3%, 3.5-3.8%, respectively, after 12 h (decay corrected and expressed as a percentage of total body initial activity). No adverse events were observed during the procedure and up to 3 months follow-up. CONCLUSIONS: Radiolabeling with [(111)In]oxine is a suitable method for follow-up of cell distribution during the first days after transplantation. A significant amount of CD133+ PBSC home to the heart after intracoronary injection in patients with CIHD. The results of this study are useful for the design of trials that evaluate the tissue repair potential of CD133+ PBSC in the setting of CIHD.

Contrast harmonic imaging improves the evaluation of left ventricular function in ventilated patients: comparison with transesophageal echocardiography.

AIMS: The study examined the value of contrast echocardiography (CE) in the assessment of left ventricular (LV) wall motion in ventilated patients in comparison with transesophageal (TOE) and standard fundamental transthoracic imaging (SE). METHODS: Transthoracic echocardiograms were done in 40 ventilated patients. Wall motion was evaluated using the recommendations of the American Society of Echocardiography on SE, CE and TOE. A visualization score was assigned on a scale of 2-0 for each of 16 segments. The segment was assigned a value of 2 if the segment was seen in both systole and diastole, 1 if seen only in systole or diastole, and 0 if not seen at all. A confidence score was also given for each segment with each technique (unable to evaluate; not sure; sure). The ejection fraction (EF) was estimated visually for each technique, and a confidence score was also applied to the EF. RESULTS: Visualization score 0 was present in 6.2 segments/patient on SE, 1.2 on CE (P<0.0001) and 1.1 on TOE (P<0.0001). An average of 6.5 segments were read with surety on SE, 11.5 on CE (P<0.0001) and 12.3 on TOE ( P<0.0001 ). There was no significant difference for CE vs TOE. EF was uninterpretable in 32% on SE, 0% on CE (P<0.001 and 0% on TOE (P<0.001). The EF was read with surety in 53% of patients on SE, 88% on CE (P < 0.0001) and 93% with TOE (P<0.0001) with no difference for CE vs TOE. Thus, wall motion was seen with more confidence on CE and TOE. CONCLUSIONS: In the ventilated patients with suboptimal transthoracic echocardiograms for the evaluation of the LV function, CE provides image quality of regional and global LV function similar to that achieved with TOE echocardiography.

Influence of posture on haemodynamics, sodium and hormonal homeostasis in cirrhotic patients with and without ascites.

BACKGROUND/AIMS: Previous studies in preascitic cirrhosis demonstrated sodium retention during upright posture and sodium hyperexcretion during bed-rest. In patients with ascites, sodium excretion and creatinine clearance decreased during upright posture. Head-down tilting (HDT) accentuated the natriuretic effect of bed-rest in short term studies. The aim of this study was to evaluate the effects of prolonged change in posture on sodium homeostasis and on haemodynamics in cirrhotic patients. METHODS: Eighteen cirrhotic patients (9 with, 9 without ascites), were studied during 12 h upright, supine and HDT position (-10 degrees). During each position, 12 h urine collections were performed and blood samples were obtained before and after change in position. Non-invasive systemic hemodynamic measurements were performed. RESULTS: There was no significant difference between HDT and supine position in both ascitic and preascitic groups for urinary volume, fractional sodium excretion, creatinine clearance, urinary and plasma hormones and hemodynamics. Urinary volume (in supine and HDT) and fractional sodium excretion (in supine) were significantly higher and urinary noradrenaline and plasma renin (in supine and HDT) significantly lower in the preascitic group compared with the ascitic patients. Cardiac output and heart rate decreased after 12 h supine and HDT, suggesting a deactivation of sympatic nervous system and catecholamines. CONCLUSION: Our results demonstrate that prolonged HDT had no advantage over normal bed-rest in both patient groups. Possibly, a short-term beneficial effect of HDT was lost after several hours.

Heart valvular disease in patients with Parkinson's disease treated with high-dose pergolide.

The authors report the clinical, echocardiographic, and pathologic findings in two patients treated with more than 5 mg of pergolide daily who developed symptomatic severe heart failure due to restrictive valvular disease. They also describe the echocardiographic data of another eight patients taking similar doses of pergolide presenting no clinical signs of heart failure. The findings suggest a possible role of high doses of pergolide in inducing restrictive valvular disease.

Native valve endocarditis with aorta-to-left atrial fistula due to Corynebacterium amycolatum.

Infective endocarditis remains a pathology with a high rate of complications and mortality. One of the most dramatic complications is abscess formation. A rare evolution of abscess formation is the development of fistula. We describe an 88-year-old woman with an aortic root abscess and aorta-to-left atrial fistula. To our knowledge this has only been described with streptococcus species as causative micro-organism. In this case the abscess was caused by Corynebacterium amycolatum, which is an infrequently found micro-organism.

Comparison of transthoracic echocardiography with second harmonic imaging with transesophageal echocardiography in the detection of right to left shunts.

We compared the use of transthoracic echocardiography with second harmonic imaging after a peripheral intravenous injection of an agitated saline solution with transesophageal echocardiography (TEE) in the detection of right to left shunts at the cardiac and pulmonary level. Second harmonic mode transthoracic echocardiography and TEE are equally sensitive in detecting right to left shunts in patients undergoing a daily routine TEE.

Tricuspid stenosis: a rare complication of pacemaker-related endocarditis.

We report a case of recurrent pacemaker lead endocarditis as the cause of acquired tricuspid stenosis. The diagnosis was made noninvasively by 2-dimensional Doppler echocardiography. The case was further complicated by a paradoxical septic embolism through a patent foramen ovale. This cascade of rear events after a pacemaker implantation has never been described in the literature before.

Impact of second harmonic imaging on the determination of the global and regional left ventricular function by 2D echocardiography: a comparison with MIBI gated SPECT.

AIMS: To evaluate the impact of second harmonic (SH) compared to fundamental mode (FM) imaging on the echocardiographic determination of ejection fraction (EF) and wall motion score index (WMSI), using MIBI gated SPECT as an independent reference. METHODS: Sixty-two consecutive patients underwent an echocardiography study and a MIBI gated SPECT over 24 hours. EF was estimated visually (estimated-E) and was calculated with the Simpson biplane method (Tracing-T), for both FM and SH. WMSI was determined by two independent echo-readers blinded to the nuclear imaging results. The same segmentation and scoring system was used for WMSI determined by MIBI gated SPECT. RESULTS: The percentages of unscored segments because of suboptimal endocardial border detection were 19.5% (FM) and 9.0% (SH). The correlation coefficients (r) between SPECT-EF and echo-EF were: FM (E)=0.705, FM (T)=0.546, SH (E)=0.771, SH (T)=0.743. Agreement between SPECT-EF and echo-EF was acceptable for both imaging modalities (mean of the difference +/- 2 S.D.): -2.8 +/- 18.5 (FM) and -3.5 +/- 16.4 (SH). Correlation coefficients (r) between WMSI calculated by SPECT and by echo were 0.715 (FM) and 0.789 (SH). Agreement between SPECT-WMSI and echo-WMSI was good for all imaging modes but better with SH compared to FM: 0.12 +/- 0.91 (FM), 0.10 +/- 0.77 (SH). The interobserver correlation coefficients (r) for the WMSI were 0.939 (FM) and 0.996 (SH). The agreement between the two observers was better for SH compared to FM. The systematic differences (mean differences) were 0.21 (FM) and -0.01 (SH), and the random differences between both observers (2 S.D.) decreased from 1.55 (FM) to 0.29 (SH). CONCLUSIONS: The use of SH echocardiography decreases the number of unscored segments. This results in an important gain in correlation and agreement for EF determination between echo and SPECT, and in a considerable decline of the interobserver variability for the echo-determined WMSI. WMSI determined by MIBI gated SPECT correlated closely with the SH WMSI, and agreement between both methods was excellent.

Pulmonary stenosis caused by extrinsic compression of an aortic pseudoaneurysm of a composite aortic graft.

Pulmonic stenosis and stenosis of the right ventricular outflow tract related to extrinsic compression have been described in patients with tumors, in a patient with a pericardial cyst, and in patients with vascular abnormalities as an unruptured sinus of Valsalva aneurysm, a giant coronary artery pseudoaneurysm and an aortic arch aneurysm. Composite graft replacement of the ascending aorta and aortic valve with reimplantation of the coronary arteries has some inherent complications. Our case report describes a patient with a pericomposite graft aneurysm presenting as a stenosis of the pulmonary artery, detected by Doppler echocardiography.

Quantitative assessment of regional dysfunction from gated single photon emission tomography myocardial perfusion studies: a non-segmental approach.

We present a modified (non-segmental) method for quantification of regional left ventricular dysfunction using gated myocardial perfusion SPET. Gated SPET is increasingly used to obtain complementary information on local perfusion and to assess the relevance of deficits in segmental count densities (attenuation vs perfusion deficit). The non-segmental approach was motivated by a hypothetical limitation regarding the validity of commonly used methods of quantitative wall thickening (WT) analysis. These methods are all based on segmental analysis, which could cause underestimation of 'true' contractile dysfunction in perfusion defects that do not have a strict segmental distribution. SPET images gated in eight time bins 60 min after the injection of 740 MBq 99Tcm-tetrofosmin or 99Tcm-sestamibi were recorded on a triple-headed camera in 20 normal subjects and in 16 patients within 2 weeks and again 3 months after myocardial infarction. Normal limits of wall thickening, calculated from pooled wall thickening profiles obtained in normal subjects, were used to identify and quantify areas with abnormal wall thickening in patients with coronary artery disease. The method was validated against data obtained from contrast ventriculography (CVG) and tested for reproducibility. The reproducibility of the method was excellent: r = 0.98 (WTsev measure 1 = 1.03WTsev measure 2 - 0.01). The localization of wall thickening abnormalities detected by gated SPET correlated well with the localization of regions with abnormal wall motion (WM) identified by CVG. The severity of the regional myocardial dysfunction assessed by gated SPET was closely correlated with the severity of the regional myocardial dysfunction derived from CVG: r = 0.85 (WMsev = 2.55WTsev + 2.30). Furthermore, a good correlation between the total wall thickening severity score and the global left ventricular ejection fraction (LVEF) was observed early and late after myocardial infarction: r = 0.80 (WTsev = -0.4LVEF + 0.46). We conclude that quantitative analysis of regional wall thickening assessed from gated SPET myocardial perfusion scintigraphy is a reliable parameter for regional ventricular function. Categorizing wall thickening abnormalities quantitatively may be helpful in assessing small changes in regional function that may occur between sequential gated SPET images.

Dipyridamole-induced angina pectoris during sestamibi stress test in patients with significant coronary artery disease: clinical, angiographic, and nuclear determinants.

Intravenous dipyridamole induces angina pectoris (AP) in some patients with significant coronary artery disease (CAD). The aim of this prospective study was to identify the angiographic, nuclear, and clinical determinants. The authors examined 50 patients consecutively with significant CAD on coronary angiography. All antiischemic medications were stopped twenty-four hours (nitrates only 6 hours) before injection of dipyridamole (0.84 mg/kg). ECGs were taken before, during, and after this injection. The regional myocardial activity of Tc-99m-Sestamibi at rest and after dipyridamole injection was measured with single-photon emission computed tomography (SPECT). During dipyridamole injection 20 patients had AP, of whom 15 had ST segment depression on ECG (P < 0.001). The only significant difference on coronary angiography between patients with dipyridamole-induced AP and those without AP was the presence of collaterals (P < 0.05). In patients with AP and collaterals, ECG and SPECT changes were always noted in the collateralized territory. Subgroup analysis showed that patients without previous myocardial infarction (MI, n = 17, P < 0.05) or nontransmural MI (n = 17, P < 0.05) had a good correlation between collaterals and AP, whereas patients with a history of transmural MI (n = 16) did not. No further significant variables could be found as a predictor of AP after dipyridamole injection. These findings suggest that AP during dipyridamole stress test is due to ischemia, which is not related to the severity of CAD. Ischemia is probably due to coronary steal to the collateralized territory in patients without transmural MI. Dipyridamole-induced angina pectoris is predictive for collaterals and may indicate viability in patients with MI.

Early electrocardiographic signs in acute massive pulmonary embolism.

As a result of the increasing accuracy in diagnosing acute pulmonary embolism by isotopic ventilation-perfusion scintigraphy and pulmonary arterial angiography, the electrocardiographic changes associated with acute cor pulmonale are being abandoned as a diagnostic tool for this life-threatening disease. Nevertheless, certain electrocardiographic findings can raise the suspicion of pulmonary embolism. In our view the electrocardiogram does have some merits in the emergency work-up of a patient with a high suspicion of pulmonary embolism. In this case report we emphasize the importance of the electrocardiographic findings which forwarded the diagnosis of pulmonary embolism. Hence the necessary invasive diagnostic and therapeutic measures, i.e. pulmonary arterial angiography and thrombolytic therapy, can be taken immediately after admission to the emergency department.

Effect of multiple doses of losartan on the pharmacokinetics of single doses of digoxin in healthy volunteers.

1. Losartan (DuP 753, MK-954) is a novel, potent and highly selective AT1 angiotensin II receptor antagonist. The effect of multiple oral doses of losartan on digoxin pharmacokinetics was evaluated in healthy male subjects. 2. In a double-blind and randomized fashion, subjects received 50 mg losartan or placebo once daily for 15 days in each period. At least 7 days elapsed between the two treatment periods. On days 4 and 11 of each period, subjects also received a single 0.5 mg dose of digoxin intravenously and orally respectively. 3. Eleven of 13 subjects completed the study. Side effects were mild and transient (12 out of 13 subjects reported at least one adverse experience). During the study, no laboratory abnormalities were noted. 4. Multiple oral doses of losartan (50 mg daily) did not affect the pharmacokinetic parameters of 0.5 mg of digoxin i.v. AUC(0.48h) of immunoreactive digoxin during losartan 28.8 +/- 2.9 vs 28.5 +/- 3.9 ng ml-1 h during placebo; not significant, and 96 h urinary excretion [% dose] during losartan 54.0 +/- 7.2 vs 51.9 +/- 6.5% during placebo; not significant). Geometric mean ratios (90% confidence interval) for AUC and urinary excretion were respectively, 1.03 (0.98, 1.08) and 1.09 (0.98, 1.21). 5. Multiple oral doses of losartan did not affect the pharmacokinetic parameters of oral digoxin AUC(0.48 h) during losartan 23.6 +/- 3.7 ng ml-1 h vs 22.4 +/- 2.6 ng ml-1 h during placebo; not significant, Cmax 3.5 +/- 0.7 ng ml-1 with vs 3.1 +/- 0.5 ng ml-1 without losartan; not significant and tmax 0.6 +/- 0.2 h with vs 0.9 +/- 0.7 h without losartan; not significant, and 96 h urinary excretion [% dose] during losartan 51.2 +/- 6.3 vs 46.3 +/- 2.4% during placebo; not significant). Geometric mean ratios (90% confidence interval) for AUC and urinary excretion were respectively, 1.06 (0.98, 1.14) and 1.12 (0.97, 1.28). 6. We conclude that multiple oral doses of losartan (50 mg daily) do not alter the pharmacokinetics of immunoreactive digoxin, following either intravenous or oral digoxin. Furthermore, the co-administration of digoxin with losartan is well tolerated by healthy male volunteers.

Single dose pharmacokinetics, safety and tolerability of MK-0476, a new leukotriene D4-receptor antagonist, in healthy volunteers.

MK-4076 or sodium 1-(1(R)-(3-(2-(7-chloro-2-quinolinyl)-(E)- ethenyl)phenyl) 3-(1-hydroxy-1-methylethyl)phenyl)propyl)thio)methyl) cycloproprane) acetate is a novel, potent, and specific LTD4-receptor antagonist. The safety, tolerability and plasma drug profiles of single oral doses of MK-0476 (capsules) were evaluated in 18 healthy male volunteers assigned to one of the two parallel 9-subject panels. Under fasting conditions, increasing single doses of 20 to 800 mg were administered in a first part of the study and in a second part, 200 mg MK-0476 was given either as a solution, under fasting conditions, or as capsules, after a standard breakfast. All volunteers completed the study. Side effects, reported by the investigator to be related to study drug, were mild and transient. No laboratory abnormalities were noted. In the evaluated dose range of MK-0476 (20 to 800 mg) the median value of tmax ranged from 2 to 4 h, while the apparent t1/2 value averaged 4 to 5 h. The median tmax value of the 200 mg capsule dose was not significantly different from the median tmax of the 200 mg oral solution dose indicating that neither disintegration nor dissolution is a rate-limiting step for the absorption of MK-0476 from capsules. There was a statistically significant increase in the AUC (geometric mean ratio of fed/fast was 2.52 with 95% confidence interval of 1.25, 5.06) and in Cmax (geometric mean ratio of fed/fast was 1.36 with 95% confidence interval of 0.60, 3.04) when MK-0476 was given together with a breakfast, suggesting an increase in bioavailability.(ABSTRACT TRUNCATED AT 250 WORDS)