Thermodynamic characterization of naturally occurring RNA tetraloops.

Although tetraloops are one of the most frequently occurring secondary structure motifs in RNA, less than one-third of the 30 most frequently occurring RNA tetraloops have been thermodynamically characterized. Therefore, 24 stem-loop sequences containing common tetraloops were optically melted, and the thermodynamic parameters DeltaH degrees , DeltaS degrees , DeltaG degrees (37,) and T(M) for each stem-loop were determined. These new experimental values, on average, are 0.7 kcal/mol different from the values predicted for these tetraloops using the model proposed by Vecenie CJ, Morrow CV, Zyra A, Serra MJ. 2006. Biochemistry 45: 1400-1407. The data for the 24 tetraloops reported here were then combined with the data for 28 tetraloops that were published previously. A new model, independent of terminal mismatch data, was derived to predict the free energy contribution of previously unmeasured tetraloops. The average absolute difference between the measured values and the values predicted using this proposed model is 0.4 kcal/mol. This new experimental data and updated predictive model allow for more accurate calculations of the free energy of RNA stem-loops containing tetraloops and, furthermore, should allow for improved prediction of secondary structure from sequence. It was also shown that tetraloops within the sequence 5'-GCCNNNNGGC-3' are, on average, 0.6 kcal/mol more stable than the same tetraloop within the sequence 5'-GGCNNNNGCC-3'. More systemic studies are required to determine the full extent of non-nearest-neighbor effects on tetraloop stability.

Intracardiac Echocardiography to Diagnose Bioprosthetic Pulmonary Valve Thrombosis.

A 48-year-old woman presented with heart failure and bioprosthetic pulmonary valve regurgitation 2 years after pulmonary valve replacement. Intracardiac echocardiography demonstrated uniform thickening of a single prosthetic valve leaflet suggesting leaflet thrombosis rather than bioprosthetic valve degeneration. After 3 months of anticoagulation, valve regurgitation and symptoms improved. (Level of Difficulty: Intermediate.).

Ruptured Sinus of Valsalva Aneurysm Causing Aorto-Atrial Fistula and Acute Heart Failure: A Rare Encounter.

A ruptured sinus of Valsalva aneurysm as a cause of aorto-atrial fistula is very rare. We present the case of a 53-year-old female who presented with symptoms of acute heart failure and suspicion of an aorto-atrial fistula found on a transthoracic echocardiogram, which was confirmed on transesophageal echocardiography. A coronary angiogram showed normal coronary arteries but confirmed the right aorto-atrial fistula on aortogram. She underwent successful surgical repair of the fistula. Her postoperative echocardiogram showed a normal right atrium and right ventricle with no shunt. A ruptured sinus of Valsalva aneurysm is a devastating event and presents as acute heart failure. Prompt diagnosis and surgical repair is necessary to prevent mortality. LEARNING POINTS: A ruptured sinus of Valsalva aneurysm causing an aorto-atrial fistula can present as acute heart failure.A transthoracic echocardiogram can identify the presence and location of a sinus of Valsalva aneurysm, while a transesophageal echocardiogram can recognize fistulous tract formation. Cardiac magnetic resonance imaging and computed tomography can confirm or better categorize echocardiographic findings.The management of an aorto-atrial fistula is surgical intervention, involving a patch repair.

Anti-anginal medication titration among patients with residual angina 6-months after chronic total occlusion percutaneous coronary intervention: insights from OPEN CTO registry.

AIMS: Chronic total occlusion (CTO) percutaneous coronary intervention (PCI) has been shown to reduce angina and improve quality of life, but the frequency of new or residual angina after CTO PCI and its relationship with titration of anti-anginal medications (AAMs) has not been described. METHODS AND RESULTS: Among consecutive CTO PCI patients treated at 12 US centres in the OPEN CTO registry, angina was assessed 6 months after the index PCI using the Seattle Angina Questionnaire (SAQ) Angina Frequency scale (a score <100 defined new or residual angina). We then compared the proportion of patients with AAM escalation (defined as an increase in the number or dosage of AAMs between discharge and follow-up) between those with and without 6-month angina. Of 901 patients who underwent CTO PCI, 197 (21.9%) reported angina at 6-months, of whom 80 (40.6%) had de-escalation, 66 (33.5%) had no change, and only 51 (25.9%) had escalation of their AAM by the 6-month follow-up. Rates of AAM escalation were similar when stratifying patients by the ultimate success of the CTO PCI, completeness of physiologic revascularization, presence or absence of angina at baseline, history of heart failure, and by degree of symptomatic improvement after CTO PCI. CONCLUSIONS: One in five patients reported angina 6 months after CTO PCI. Although patients with new or residual angina were more likely to have escalation of AAMs in follow-up compared with those without residual symptoms, only one in four patients with residual angina had escalation of AAMs. Although it is unclear whether this finding reflects maximal tolerated therapy at baseline or therapeutic inertia, these findings suggest an important potential opportunity to further improve symptom control in patients with complex stable ischaemic heart disease.