Survival and quality of life benefit after endoscopic management of malignant central airway obstruction

Although interventional management of malignant central airway obstruction (mCAO) is well established, its impact on survival and quality of life (QoL) has not been extensively studied.We prospectively assessed survival, QoL and dyspnea (using validated EORTC questionnaire) in patients with mCAO 1 day before interventional bronchoscopy, 1 week after and every following month, in comparison to patients who declined this approach. Material/Patients/Methods: 36 patients underwent extensive interventional bronchoscopic management as indicated, whereas 12 declined. All patients received full chemotherapy and radiotherapy as indicated. Patients of the 2 groups were matched for age, comorbidities, type of malignancy and level of obstruction. Follow up time was 8.0±8.7 (range 1-38) months.Mean survival for intervention and control group was 10±9 and 4±3 months respectively (p=0.04). QoL improved significantly in intervention group patients up to the 6(th) month (p<0.05) not deteriorating for those surviving up to 12 months. Dyspnea decreased in patients of the intervention group 1 month post procedure remaining reduced for survivors over the 12th month. Patients of the control group had worse QoL and dyspnea in all time points.Interventional management of patients with mCAO, may achieve prolonged survival with sustained significant improvement of QoL and dyspnea

Conformational flexibility within the small domain of human serine racemase

Serine racemase (SR) is a pyridoxal 5′-phosphate (PLP)-containing enzyme that converts L-serine to D-serine, an endogenous co-agonist for the N-methyl-D-aspartate receptor (NMDAR) subtype of glutamate ion channels. SR regulates D-serine levels by the reversible racemization of L-serine to D-serine, as well as the catabolism of serine by α,β-elimination to produce pyruvate. The modulation of SR activity is therefore an attractive therapeutic approach to disorders associated with abnormal glutamatergic signalling since it allows an indirect modulation of NMDAR function. In the present study, a 1.89 Å resolution crystal structure of the human SR holoenzyme (including the PLP cofactor) with four subunits in the asymmetric unit is described. Comparison of this new structure with the crystal structure of human SR with malonate (PDB entry 3l6b) shows an interdomain cleft that is open in the holo structure but which disappears when the inhibitor malonate binds and is enclosed. This is owing to a shift of the small domain (residues 78–155) in human SR similar to that previously described for the rat enzyme. This domain movement is accompanied by changes within the twist of the central four-stranded β-sheet of the small domain, including changes in the φ–ψ angles of all three residues in the C-terminal β-strand (residues 149–151). In the malonate-bound structure, Ser84 (a catalytic residue) points its side chain at the malonate and is preceded by a six-residue β-strand (residues 78–83), but in the holoenzyme the β-strand is only four residues (78–81) and His82 has φ–ψ values in the α-helical region of the Ramachandran plot. These data therefore represent a crystallographic platform that enables the structure-guided design of small-molecule modulators for this important but to date undrugged target

Anomalous Left Circumflex Coronary Artery: Not Always Benign. A Worm-Like Thrombus Can Be Housed in This Most Common Coronary Anomaly

A case of an anomalous left circumflex (LCx) coronary artery originating from the right coronary ostium is presented in a patient with acute myocardial infarction, whereby a long worm-like thrombus was retrieved from the proximal segment of this artery, which was subsequently stented. This case illustrates that the anomalous LCx is not always benign, and may well predispose to an acute coronary syndrome, requiring interventional management

Cardiology News /Recent Literature Review / Mid Quarter 2012

The ESC Congress will be held in Munich, 25-29/8/2012 TCT Meeting will take place in Miami, 22-26/10/12  HCS Meeting to be held in Athens, 1-3/11/12  AHA 2012 is scheduled for Los Angeles, 3-7/11/12 TWENTE Trial: the Resolute Zotarolimus Eluting Stents are Noninferior to Xience V Everolimus Eluting Stents in Treating “Real-World” Patients with Complex Lesions and “Off-label” Indications for DES A total of 1,391 patients were randomly assigned to zotarolimus eluting stents (ZES) (n = 697) or everolimus eluting stents (EES) (n = 694). Acute coronary syndromes were present in 52% and “off-label” feature in 77% of patients. Of the lesions, 70% were type B2/C; the post-dilation rate was very high (82%). In ZES and EES, target vessel failure (TVF) occurred in 8.2% and 8.1%, respectively (absolute risk-difference 0.1%; p (noninferiority) = 0.001). The definite-or-probable stent thrombosis rates were relatively low and similar for ZES and EES (0.9% and 1.2%, respectively, p = NS). Definite stent thrombosis rates were also low (0.58% and 0%, respectively, p = NS). In EES, probable stent thrombosis beyond day 8 was observed only in patients not adhering to dual antiplatelet therapy. The authors concluded that resolute ZES were noninferior to Xience V EES in treating “real-world” patients with a vast majority of complex lesions and “off-label” indications for drug-eluting stents (DES), which were implanted with liberal use of post-dilation (von Birgelen C et al, J Am Coll Cardiol 2012;59:1350–1361). The TARGET Study: Placement of the LV Lead to the Latest Sites of Contraction and Away from the Scar Confers the Best Response to CRT   Among 220 patients receiving cardiac resynchronization therapy (CRT), the left ventricular (LV) lead was positioned at the latest site of peak contraction (as determined by echocardiographic speckle-tracking 2-dimensional radial strain imaging) with an amplitude of &gt;10% to signify freedom from scar (n=110, TARGET group), while in the control group (n=110) standard unguided CRT was performed. In the TARGET group, there was a greater proportion of responders at 6 months (70% vs 55%, p = 0.031) with an absolute difference in the primary endpoint (&gt;15% reduction in LV end-systolic volume at 6 months) of 15%. Compared with controls, TARGET patients had a higher clinical response (83% vs 65%, p = 0.003) and lower rates of the combined endpoint (all-cause mortality and heart failure–related hospitalization) (p = 0.031). The authors concluded that compared with standard CRT treatment, the use of speckle-tracking echocardiography to the target LV lead placement yields significantly improved response and clinical status and lower rates of combined death and heart failure–related hospitalization (Khan FZ et al, J Am Coll Cardiol 2012;59:1509–1518)... (excerpt

Cardiology News /Recent Literature Review

The ACC Annual Congress is slated for April 3-5, 2011 in New Orleans The HRS Annual Meeting is scheduled for May 4-7, 2011 in San Francisco Euro-PCR will take place in Paris on May 17-20, 2011 The ESC Annual Congress is slated for 27-31/8/2011 in Paris The TCT Annual Conference will be held in San Francisco 7-11/11/2011 The AHA Annual Scientific Sessions are scheduled for 12-16/11/2011 in Orlando Athens Cardiology Update 2012 is slated for April 5-7, 2012 Local Atrial Inflammation Present in Paroxysmal AF Atrial biopsies were obtained from 70 patients (age 60 ± 12 years, 49 males) undergoing radiofrequency catheter ablation for AF and 10 patients with Wolff-Parkinson-White syndrome, all undergoing trans-septal puncture. Biopsies were obtained by washing the dilator and needle used for trans-septal puncture with 20 mL sterile phosphate-buffered saline, and formalin fixed specimen were examined by immunohistochemistry for the presence of intracytoplasmic C-reactive protein. C-reactive protein was revealed in isolated atrial cardiomyocytes in 11 (73%) of 15 patients with paroxysmal AF as compared with 2 (25%) of 8 patients with persistent AF (P= 0.02). This technique for obrtaining biopsy specimen was safe and feasible. In this study, local atrial inflammation as assessed by C-reactive protein present in atrial myocytes, is more likely involved in paroxysmal rather than in persistent AF (Narducci ML et al, Europace. 2011 Mar 29. [Epub ahead of print])... (excerpt

Ticagrelor: a Novel P2Y12 Platelet Receptor Antagonist

Blockade of platelet adenosine-diphosphate (ADP) receptors has been established as a key therapeutic strategy in cardiovascular disease. Among the thienopyridines, clopidogrel decreases ischemic outcome in patients who present with acute coronary syndromes and the more potent prasugrel has been demonstrated to be superior to clopidogrel in patients who are scheduled to undergo percutaneous coronary intervention. However, the antiplatelet potency is also associated &nbsp;&nbsp;with an increased risk of bleeding complications, and the irreversible ADP receptor antagonism has potential implications especially in the setting of coronary by-pass operation. Ticagrelor is a new reversible antagonist of the P2Y12 receptor, which seems to be more effective and at the same time equally safe to the so far established antiplatelet regimens. This article reviews the current data on this novel compound focusing on its advantageous pharmacology and the clinical results provided by the first phase IIb and III trials

Does a Short QT Interval Presage a Short Life Span?

A case of a 16-year old adolescent is presented who was referred for investigation of a syncopal episode. The ECG displayed a very short QT interval of 280 ms, compatible with the newly described short QT syndrome, which is genetic primary electrical disease of abnormal potassium currents responsible for the repolarization process of the cardiac muscle. The prognosis is similar to the other well known familial cardiac channelopathies, such as the long QT or the Brugada syndromes which are associated with a high risk of sudden cardiac death, requiring an implantable cardioverter defibrillator device for life-long protection

Novel Technology for Ablation of Atrial Fibrillation Using Multi- Electrode Catheters and Duty-Cycled Radiofrequency Energy

These are fluoroscopic views of the heart demonstrating the use of novel technology for catheter ablation of atrial fibrillation (AF) in a patient who has had frequent episodes of paroxysmal AF and had failed antiarrhythmic drug therapy. In the upper panels, a steerable guiding catheter has been introduced via a transseptal approach into the left atrium and inserted into the right upper (left upper panel) and left upper (right upper panel) pulmonary veins (PVs), which are visualized with hand injection of contrast material. Subsequently, through the same guiding catheter, another deflectable circular multi-electrode (decapolar) 9-F catheter is inserted over a guide-wire and stabilized at the antrum of each PV (lower panels). Via this catheter, simultaneous mapping and ablation is performed by delivering duty-cycled unipolar and bipolar radiofrequency (RF) energy at 4-10 Watts with use of a multichannel RF generator. Thus, electrical isolation of the PVs is effected by delivering RF energy simultaneously to multiple points in the perimetry of the PV antrum, rather than employing extensive point-by-point or stepwise ablation with use of conventional single electrode catheters. With this novel technology, the procedure appears potentially safer and more efficiently performed with a shorter procedural time in a simplified approach compared with the conventional single-electrode catheter technique

Long Term Beneficial Effects of Good Glycemic Control on Macrovascular Disease: Results from UKPDS 10-Year Post Trial Monitoring

Cardiovascular disease is a significant cause of morbidity and mortality in patients with diabetes mellitus. The impact of tight glycemic control in the mortality has been investigated in large randomized clinical trials. The data are controversial, as some trials (ACCORD, ADVANCE and VADT) have found that intensive glycemic control either has no impact on cardiovascular outcomes or even worsens them. On the other hand, results of the 10-year follow-up of the UKPDS study suggest that tight glycemic control of younger, newly diagnosed patients with type 2 diabetes may have long term beneficial cardiovascular effects. All these data have led to the adoption of clinical guidelines suggesting a different strategy according to the patient’s age and duration of diabetes