Prognostic relevance of serum thymidine kinase in primary myelodysplastic syndromes: relationship to development of acute myeloid leukaemia

The aim of this study was to evaluate the possible prognostic relevance of thymidine kinase serum levels (s-TK), an indirect marker of proliferative activity, in myelodysplastic syndromes (MDS). S-TK levels were monitored by means of a radioenzyme assay in 90 patients affected by MDS (22 refractory anaemia, RA; 17 RA with ring sideroblasts, RARS; 21 RA with blast excess, RAEB; 15 RAEB in transformation, RAEB-T; 15 chronic myelomono-cytic leukaemia, CMMoL). Mean s-TK levels (U//tl) measured at diagnosis were 11–9 –12–6 for RA, 11–4–13'6 for RARS, 19–9 – 28–4 for RAEB, 39–6 – 34–3 for RAEB-T and 77–7 – 69–7 for CMMoL (normal values <5U//LI1). With the only exception of a weak relationship with lactate dehydrogenase, no correlation was found between initial s-TK values and other clinical or laboratory parameters, such as age, haemoglobin, white blood cell or platelet count, percentage of bone marrow blasts. MDS patients with s-TK >38 V/fA , a cut-off level selected by means of ROC statistical analysis, showed a significantly shorter survival than those with s-TK <38U//xl (8–2 v 37–4 months, respectively; P < 0–0001). In particular, transformation in acute myeloid leukaemia (AML) occurred in 17/21 (81%) of patients with s-TK >38U//d and 9/69 (13%) of those with lower levels at diagnosis (P < 00001), independently of FAB subtype. High s-TK levels were also useful to predict evolution in AML during the course of the disease in patients with normal initial values. Multivariate analysis confirmed the independent prognostic value of s-TK on both overall survival and risk of acute transformation. We conclude that s-TK may be an important prognostic factor in MDS, strongly correlated with development of AML.     

Bile lipid composition and haemostatic variables in a case of high density lipoprotein deficiency (Tangier disease)

A 62-year-old man with clinical and biochemical findings consistent with homozygous Tangier disease is presented. Widespread atherosclerosis was present. Bile lipid analysis showed a low molar percentage of cholesterol with a low saturation index. The data suggest that high density lipoprotein cholesterol may act as a preferential precursor of biliary cholesterol. Coagulation and platelet studies indicated that the patient's platelets were hyper-responsive to aggregating agents and produced an increased amount of thromboxane B2. A platelet storage pool deficiency was also found.     

The Feasibility of Fully Automated Pacemaker Advise in Treating Atrial Tachyarrhythmias

Background: Modern pacemakers continuously store significant cardiac‐related events. Interpreting these data and reprogramming the pacemaker can be time‐consuming and demands expert knowledge. A software‐based expert system, the therapy advisor (TA), was developed, which analyzes stored data and provides reprogramming recommendations. This study addresses whether pacemaker experts consider the messages that are automatically generated appropriate in the management of atrial tachyarrhythmias/atrial fibrillation (AT/AF). Methods: This observational, international, multicenter study follows 150 patients with suspected or documented atrial arrhythmias who received a dual‐chamber pacemaker (model Vitatron T‐70, Medtronic Inc., Minneapolis, MN, USA) incorporating the TA. The TA summarizes technical and clinical data stored in the pacemaker into key messages and may suggest programming changes. Twenty‐five cardiologists examined their patients per normal practice during two follow‐up visits. They reported the therapy changes they deemed necessary without initially reviewing the TA messages. Next, they rated their satisfaction with and the clinical relevance of the TA messages and recorded the final therapy changes. Results: The TA generated (mostly AT/AF‐related) main observations in 49% and programming advice in 33% of the patients. The experts rated 95% of the TA messages as satisfactory and deemed therapy changes necessary in roughly half the patients. Pacemaker changes in AT/AF therapy or general settings were prompted primarily by the diagnostic information stored in the device. Medication changes were mostly led by the symptoms reported by the patient. Conclusion: This study demonstrates that experienced cardiologists agree with 95% of the observations and programming suggestions that the TA automatically generates. (PACE 2010; 605–614)     

Programmed cell death in the pancreas of Bufo bufo during metamorphosis

Programmed cell death or apoptosis occurred in anuran amphibian larval pancreas as a remodelling agent, and was responsible for the reduction of the gland volume during metamorphosis. Apoptotic cells were recognisable by their morphological characteristics and could be immunocytochemically detected by means of the TUNEL reaction, which evidenced nuclear DNA fragmentation. During the last stages of prometamorphosis, that is in the period of hindlimb differentiation, only a few TUNEL positive cells occurred, whereas they increased at the beginning of metamorphic climax, that is at forelimb emergence and during tail regression. Under the electron microscope, the typical morphological characteristics of apoptosis were observed: decrease in size, and the presence of wide intercellular spaces and nuclei with dense chromatin masses arranged in crescents. The fragmentation of these cells produced the so-called 'apoptotic bodies': portions of cytoplasm lined by a membrane, containing nuclear fragments and cytoplasmic organites. Dead cell elimination is hypothesised to occur by phagocytic ingestion.     

Successful Radiofrequency Ablation of an Accessory Pathway During Pregnancy

The preexcitation syndrome is a rare entity during pregnancy. We present a 20-week pregnant patient with Wolff-Parkinson-White syndrome and recurrent episodes of tachycardia with hemodynamic compromise refractory to medical treatment that required electrical cardioversion several times. Due to the poor evolution we performed a successful radiofrequency ablation of a right posteroseptal accessory pathway using 70 seconds of total fluoroscopy time without complications. We consider this is an alternative and safer treatment in those cases in which the tachyarrhythmias compromise the hemodynamic state during pregnancy.     

Electroanatomic Mapping and Ablation of Macroreentrant Atrial Tachycardia: Comparison Between Successfully and Unsuccessfully Treated Cases

Ablation of Macroreentrant Atrial Tachycardia. Introduction: Ablation of macroreentrant atrial tachycardia (MRAT) is demanding and identification of predictors of failure may be of help in patient management. This study compares the characteristics of successfully versus unsuccessfully treated patients undergoing electroanatomic mapping (EAM) and ablation of MRAT. Methods and Results: Consecutive patients undergoing EAM and ablation of MRAT were included. Ablation was linearly placed at the mid‐diastolic isthmus (MDI) to achieve arrhythmia interruption and conduction block. Variables were analyzed for predictors of both procedural failure and cumulative failure (procedural failure + early recurrences). Fifty‐two patients (37 M; age 64 ± 16 years) with 56 MRATs were considered. The MRAT was in the right atrium in 25 morphologies (45%) and 32 (57%) showed a double‐loop reentry. Fifty‐one morphologies (91%) in 47 patients were successfully treated; 3 patients had early recurrences of the same MRAT. None of the clinical variables considered significantly differed in the successfully treated group as compared to the unsuccessfully treated. Conversely, there was a significant difference as to the EAM characteristics: successfully treated cases showed a narrower target isthmus with a lower voltage amplitude and slower conduction velocity (CV). In the MDI, a CV >60 cm/sec and a width >40 mm were the strongest predictors of procedural failure and cumulative failure, respectively. Conclusions: In this patient population, while the clinical variables did not differ significantly, there was a significant difference in the EAM characteristics between successfully and unsuccessfully treated cases. CV and width of the isthmus target for ablation were the strongest independent predictors of procedure outcome. (J Cardiovasc Electrophysiol, Vol. 21, pp. 155‐162, February 2010)     

Long-Term Performance of Endocardial Pacing Leads

To assess the performance of endocardial pacemaker leads and to identify factors associated with structural lead failure, medical records of 2,611 endocardial pacing leads (in 1, 5W patients) implanted between 1980 and 1991, having at least 1 month of follow-up, were reviewed. Leads without structural failure had normal function at the last follow-up date, or were discontinued for reasons other than structural failure (patient death, infection, dislodgment, lead-pacemaker incompatibility, operative complication, or abandonment by telemetry not related to failure). Leads with suspected structural failures were invasively or noninvasively disconnected because of clinical malfunction (loss of capture or sensing, oversensing, elevated thresholds, or skeletal muscular stimulation). Leads with verified structural failures met the criteria for suspected lead failure and also had a visible defect seen in the operating room or on chest roentgenograms, a change in the impedance interpreted by the physician as lead disruption, or a manufacturer's return product report that confirmed structural failure. Variables analyzed included patients’ age and gender, paced chamber, venous access, insulation materials, fixation mechanism, coaxial design, polarity, and different lead models. The cumulative lead survival at 5 and 10 years were 97.4% and 92.9%, respectively, for suspected failures; and 98.7% and 97.3%, respectively, for verified failures. Leads in older patients (≥ 65 years old), and leads in atrial position had fewer verified failures (P = 0.014 and P = 0.007, respectively). Unipolar leads also tended to perform better according to the verified definition (P = 0.07). The lead Medtronic 4012 had more suspected (P < 0.05) and more verified failures (P < 0.01), the lead CPI 4010 had more verified failures (P < 0.05) than the entire group of ventricular leads. Conclusions: Endocardial pacing leads implanted in atrial position, and implanted in older patients (> 65 years old) seems to have better long-term survival. Some lead models (Medtronic 4012 and CPI 4010) had poor survival rates, that could not be explained by the analyzed variables. The expected performance of endocardial pacing leads varies according to how failure is defined.     

Long-Term Survival in Patients Treated with Cardiac Resynchronization Therapy: A 3-Year Follow-Up Study from the InSync/InSync ICD Italian Registry

Background: Studies reporting the long-term survival of patients treated with cardiac resynchronization therapy (CRT) outside the realm of randomized controlled trials are still lacking. The aim of this study was to quantify the survival of patients treated with CRT in clinical practice and to investigate the long-term effects of CRT on clinical status and echocardiographic parameters.
Methods: The study population consisted of 317 consecutive patients with implanted CRT devices from eight Italian University/Teaching Hospitals. The patients were enrolled in a national observational registry and had a minimum follow-up of 2 years. A visit was performed in surviving patients and mortality data were obtained by hospital file review or direct telephone contact.
Results: During the study period, 83 (26%) patients died. The rate of all-cause mortality was significantly higher in ischemic than nonischemic patients (14% vs 8%, P = 0.002). Multivariate analysis showed that ischemic etiology (HR 1.72, CI 1.06–2.79; P = 0.028) and New York Heart Association (NYHA) class IV (HR 2.87, CI 1.24–6.64; P = 0.014) were the strongest predictors of all-cause mortality. The effects of CRT persisted at long-term follow-up (for at least 2 years) in terms of NYHA class improvement, increase of left ventricular ejection fraction, decrease of QRS duration (all P = 0.0001), and reduction of left ventricular end-diastolic and end-systolic diameters (P = 0.024 and P = 0.011, respectively).
Conclusions: During long-term (3 years) follow-up after CRT, total mortality rate was 10%/year. The outcome of ischemic patients was worse mainly due to a higher rate of death from progressive heart failure. Ischemic etiology along with NYHA class IV was identified as predictors of death. Benefits of CRT in terms of clinical function and echocardiographic parameters persisted at the time of long-term follow-up.     

DDIR Versus VVIR Pacing in Patients with Paroxysmal Atrial Tachyarrhythmias

Patients with sinus node dysfunction (SND) in particular those with tachycardia-bradycardia syndrome and patients undergoing atrioventricular nodal ablation procedures for refractory paroxysmal atrial tachyarrhythmias (PAT), are candidates for single chamber (VVIR mode) or dual chamber rate responsive (DDIR mode) systems. To evaluate the benefits and disadvantages of each pacing mode we retrospectively analyzed 33 patients with a history of frequent PAT who received a VVIR (22 patients); or a DDDR pacemaker (11 patients) programmed to the DDIR mode. The mean follow-up time was 25 and 18 months, respectively. Preimplant left atrial diameter was significantly smaller in the DDIR group. Chronic atrial fibrillation developed in 54% of the VVIR patients and 27% of the DDIR group, but this difference was not significant. Complications of patients with VVIR pacemakers included new mitral and tricuspid insufficiency, stroke, pacemaker inlolerance and aggravated congestive heart failure. Patients with DDIR pacemakers had a lower incidence of symptoms and complications. However, this group received more antiarrhythmic medication, required a closer follow-up, and their pacemakers needed frequent reprogramming. Our findings suggest that VVIR is a poor choice for patients with SND, congestive heart failure, and PAT, and that DDIR may be an acceptable alternative.     

Fourier Analysis in Patients with Different Pacing Modes

The purpose of this study was to evaluate the usefulness of phase analysis in detecting the altered activation sequence induced by different pacing modes. Radionuclide ventriculography and planar gated blood pool scintigraphy were performed at rest in 56 patients with different pacemakers. This method permitted us to localize the pacemaker impulse site in the right ventricle and its diffusion in the heart. In patients with VVI pacemaker, this technique showed an evident asynchronism of contraction and relaxation of each ventricle and the standard deviation of phase angle (sigma), calculated by computer, is greater during pacing than sinus rhythm for left (LV) and right (RV) ventricles (LV sigma: 17 degrees +/- 4 vs 11 degrees +/- 3, less than 0.001; RV sigma: 31 degrees +/- 7 vs 14 degrees +/- 4, P less than 0.001). In the patients with VVI rate responsive pacemakers, the LV sigma changed from 18.5 +/- 3 under pacing to 11 degrees +/- 3 in sinus rhythm, P less than 0.001, while the RV sigma changed from 30 degrees +/- 8 to 14 degrees +/- 4, P less than 0.001. Instead in the patients with DDD pacemakers, the LV sigma changed from 15.5 degrees +/- 2 under pacing to 11 degrees +/- 3 in sinus rhythm, P less than 0.05, while the RV sigma changed from 29.1 degrees +/- 6 to 14 degrees +/- 4, P less than 0.001.(ABSTRACT TRUNCATED AT 250 WORDS)