A benzopyran with antiarrhythmic activity is an inhibitor of Kir3.1-containing potassium channels.

Atrial fibrillation (AF) is the most commonly diagnosed cardiac arrhythmia and is associated with increased morbidity and mortality. Currently approved AF antiarrhythmic drugs have limited efficacy and/or carry the risk of ventricular proarrhythmia. The cardiac acetylcholine activated inwardly rectifying K+ current (IKACh), composed of Kir3.1/Kir3.4 heterotetrameric and Kir3.4 homotetrameric channel subunits, is one of the best validated atrial-specific ion channels. Previous research pointed to a series of benzopyran derivatives with potential for treatment of arrhythmias, but their mechanism of action was not defined. Here, we characterize one of these compounds termed Benzopyran-G1 (BP-G1) and report that it selectively inhibits the Kir3.1 (GIRK1 or G1) subunit of the KACh channel. Homology modeling, molecular docking, and molecular dynamics simulations predicted that BP-G1 inhibits the IKACh channel by blocking the central cavity pore. We identified the unique F137 residue of Kir3.1 as the critical determinant for the IKACh-selective response to BP-G1. The compound interacts with Kir3.1 residues E141 and D173 through hydrogen bonds that proved critical for its inhibitory activity. BP-G1 effectively blocked the IKACh channel response to carbachol in an in vivo rodent model and displayed good selectivity and pharmacokinetic properties. Thus, BP-G1 is a potent and selective small-molecule inhibitor targeting Kir3.1-containing channels and is a useful tool for investigating the role of Kir3.1 heteromeric channels in vivo. The mechanism reported here could provide the molecular basis for future discovery of novel, selective IKACh channel blockers to treat atrial fibrillation with minimal side effects.

Aortic stenosis calcium scoring in a racially mixed sample.

Aortic stenosis (AS) is common and increasing in prevalence as the population ages. Using computed tomography (CT) to quantify aortic valve calcification (AVC) it has been reported that men have greater degrees of calcification than women among subjects with severe AS. These data, however, were derived in largely Caucasian populations and have not been verified in non-Caucasian subjects. This retrospective study identified 137 patients with severe AS who underwent valve replacement and had CT scans within 6 months prior to surgery. AVC scores were compared between men and women, both in the entire sample and in racial subgroups. 52% of subjects were male and 62.8% were non-Caucasian. Mean AVC score for the entire cohort was 3062.08±2097.87 with a range of 428-13,089. Gender differences in aortic valve calcification were found to be statistically significant with an average AVC score of 3646±2422 in men and 2433±1453 in women (p=0.001). On multivariate analysis, gender remained significantly associated with AVC score both in the entire sample (p=0.014) and in the non-Caucasian subgroup (p=0.008). Mean AVA was significantly greater in males than females but this difference disappeared when AVA was indexed to BSA (p=0.719). AVA was not different between racial groups (p=0.369). In this research we observed that among subjects with severe AS men have higher AVC scores than women regardless of racial background. This is consistent with previous studies in predominantly Caucasian populations.

Clinical correlates of hand-held ultrasound-guided assessments of the inferior vena cava in patients with acute decompensated heart failure.

BACKGROUND: Accurately assessing volume status in acutely decompensated heart failure (ADHF) can be challenging. Inferior vena cava (IVC) dynamics by echocardiography allow indirect assessment of volume status in these patients. Recently introduced hand-held ultrasound devices are promising. We aimed to describe the clinical correlates of volume status assessment using a hand-held ultrasound device in ADHF. METHODS: In this prospective study, we evaluated 106 patients admitted with ADHF. First scan was performed within 24 hours of admission and timed in reference to first dose of intravenous diuretic. Daily resting and inspiratory (sniff) IVC diameters were measured according to standard echocardiography methods during hospitalization including the day of discharge. IVC collapsibility index (IVC-CI = Maximum IVC diameter-Inspiratory IVC diameter/maximum diameter; <0.5 representing hypervolemia) was calculated. Primary study endpoint was 30-day readmission. Research activities were independent of clinical decision-making. RESULTS: Data for 106 patients was analyzed. Mean age was 66.7 ± 13.8 years, of which 53.8% were females, and a mean ejection fraction was 39 ± 18%. Initial scan of the IVC was obtained at an average time of 5.2 ± 8.04 hours from first diuretic dose. 81.2% of patients at admission had an IVC-CI <0.5. 63.2% patients had an IVC-CI <0.5 at discharge. There were no significant differences in age, length of stay, diuretic dose, or 30-day readmissions between patients with a discharge IVC-CI <0.5 vs ≥ 0.5. CONCLUSION: Hand-held ultrasound assessment of IVC-CI in ADHF patients, although a feasible concept, is unable to predict 30-day readmissions in our study. Further prospective studies are necessary.

Clinical utility of the HEART score in patients admitted with chest pain to an inner-city hospital in the USA.

BACKGROUND: Chest pain is one of the most common presentations to a hospital, and appropriate triaging of these patients can be challenging. The HEART score has been used for such purposes in some countries and only a few validation studies from the USA are available. We aim to determine the utility of the HEART score in patients presenting with chest pain to an inner-city hospital in the USA. PATIENTS AND METHODS: We retrospectively screened 417 consecutive patients admitted with chest pain to the observation/telemetry units at Einstein Medical Center Philadelphia. After applying inclusion and exclusion criteria, 299 patients were included in the analysis. Patients were divided into low-risk (0-3) and intermediate-high (≥4)-risk HEART score groups. Baseline characteristics, thrombolysis in myocardial infarction score, need for revascularization during index hospitalization, and major adverse cardiovascular events (MACE) at 6 weeks and 12 months were recorded. RESULTS: There were 98 and 201 patients in the low-score group and intermediate-high-score group, respectively. Compared with the low-score group, patients in the intermediate-high-risk group had a higher incidence of revascularization during the index hospital stay (16.4 vs. 0%; P=0.001), longer hospital stay, higher MACE at 6 weeks (9.5 vs. 0%) and 12 months (20.4 vs. 3.1%), and higher cardiac readmissions. HEART score of at least 4 independently predicted MACE at 12 months (odds ratio 7.456, 95% confidence interval: 2.175-25.56; P=0.001) after adjusting for other risk factors in regression analysis. CONCLUSION: HEART score of at least 4 was predictive of worse outcomes in patients with chest pain in an inner-city USA hospital. If validated in multicenter prospective studies, the HEART score could potentially be useful in risk-stratifying patients presenting with chest pain in the USA and could impact clinical decision-making.

Right ventricular function measured by TAPSE in obese subjects at the time of acute myocardial infarction and 2year outcomes.

INTRODUCTION: Obesity is associated with significantly better outcome after acute myocardial infarction (AMI), a phenomenon known as 'obesity paradox'. Tricuspid annular plane systolic excursion (TAPSE) is an echocardiographic measurement of right ventricular (RV) function and has prognostic implications at the time of AMI. METHODS: We examined the difference in RV function among patients admitted with AMI according to obesity status. In a single center cohort analysis of 105 patients admitted between 2010 and 2011 with the diagnosis of AMI. Demographic, anthropometric data and cardiovascular risk factors were prospectively collected. All subjects had echocardiogram within 48h of AMI diagnosis for TAPSE calculations. Subjects were divided into two groups based on their obesity status. RESULTS: Obese subjects had better RV function compared to non-obese, TAPSE: 19±6.6 vs. 16±4.9mm; p 0.02 at the time of AMI. There was no significant difference in TAPSE between OSA and non-OSA subjects, 19±6.3 vs. 17±6.2mm; p 0.21. After 2years of follow up, patients with obesity and better RV function were less likely to develop new onset heart failure (HF) with OR 0.30 (95% CI 0.09-0.93; p 0.03) and OR 0.31 (95% CI 0.11-0.76; p 0.007) respectively. CONCLUSION: Obese patients had better RV function measured by TAPSE at the time AMI when compared non-obese patients. Patients with better RV function at the time of AMI were less likely to develop new-onset HF and there was a trend in the obese group to less likely develop new-onset HF after 2year follow up.

Ventricular Assist Device-Related Haemolysis Presenting with Acute Pancreatitis.

Acute pancreatitis is one of the rare complications in patients fitted with a left ventricular assist device (LVAD). We herein report a case of acute pancreatitis in a patient with LVAD triggered by intravascular haemolysis. A 44-year-old man with non-ischaemic cardiomyopathy (NICM) after VAD implantation presented with epigastric pain. Laboratory work-up showed acute pancreatitis and haemolysis. As there was concern that device thrombosis was causing haemolysis, the patient was started on unfractionated heparin infusion. The patient was discharged when haemolysis and pancreatitis had resolved. To our knowledge, VAD-associated haemolysis presenting with acute pancreatitis is infrequently described in the literature. LEARNING POINTS: Our case report highlights a rare presentation of device thrombosis presenting as haemolysis and pancreatitis in a patient fitted with a ventricular assist device (VAD).Our case report aims to educate internists to keep in mind a potentially life-threatening condition when taking care of patients with VAD.Our case report highlights haemolysis as a rare cause of acute pancreatitis.

Relation Between Epicardial Adipose and Aortic Valve and Mitral Annular Calcium Determined by Computed Tomography in Subjects Aged ≥65 Years.

Epicardial adipose tissue (EAT) has been linked to coronary artery calcium deposits and atherosclerotic disease. Mitral annular (MAC) and aortic valve calcium (AVC) have also been associated with atherosclerosis. This study examined the possible relation between EAT thickness and valvular calcium deposits. We included 294 patients aged ≥65 years who had noncontrast computed tomography scans of the chest. Mean age was 76 ± 7 years; 47% were men. Using reconstructed images, EAT thickness was measured at various locations. MAC and AVC were quantified by Agatston technique. The sum of AVC and MAC was reported as the grand total score (GTS). Subjects were divided into 2 groups based on the value of GTS; GTS = 0, no cardiac calcification and GTS ≥1, cardiac calcification group. Epicardial fat (left and right atrioventricular grooves and superior interventricular groove) was significantly greater in the cardiac calcification group compared with the no cardiac calcification (all values, p <0.05). After adjusting for clinical variables including BMI, EAT at the superior interventricular groove remained significantly associated with total calcium. Left atrioventricular groove EAT demonstrated a trend toward an association with total calcium, but this did not reach statistical significance. In conclusion, epicardial fat is associated with calcium deposits of the mitral annulus and aortic valve.

Sinus venosus atrial septal defect presenting with brain abscesses in a 77-year-old immunocompetent patient.

We present a case of 77-year-old immunocompetent patient who initially presented with vertigo, nausea and vomiting, with symptoms later progressing to headaches and increased lethargy. Brain MRI revealed ring-enhancing lesions typical of abscesses in the right cerebellum. Transoesophageal echocardiogram (TEE) was performed to look for the source of his abscesses, and uncovered a sinus venosus type atrial septal defect. Cardiac CT was carried out; the patient was found to have a sinus venosus atrial septal defect with partial anomalous pulmonary venous return. Moreover, dental examination showed multiple dental caries with poor oral hygiene. The patient was started on intravenous empiric antibiotics and steroids. Subsequent brain imaging showed almost complete resolution of the abscesses. The patient's symptoms started to improve, and he was eventually sent to an intensive rehabilitation centre with future plans to surgically correct his congenital heart disease to prevent further complications.

Infective endocarditis due to Bacillus cereus in a pregnant female: A case report and literature review.

Incidence of infective endocarditis during pregnancy is around 0.006% with high maternal and fetal mortality. Bacillus cereus is an extremely rare cause for endocarditis in intravenous drug abusers (IVDA) or those with valvular disease or devices such as pacemakers. We report a case of B. cereus endocarditis, which, to the best of our knowledge, has never been reported in pregnancy. A 30-year-old, 25-week pregnant female presented with right shoulder pain, swelling and erythema on the lateral aspect of deltoid muscle from large abscess over her deltoid muscle. She was found to have a vegetation on the native tricuspid valve. Cultures from abscess fluid and blood cultures grew B. cereus, she was appropriately treated with antimicrobials and had favorable outcomes. There are <20 cases of B. cereus endocarditis reported but none during pregnancy. When cultures grow unusual organisms the case must be thoroughly investigated. This case illustrates a rare situation (endocarditis in pregnancy) with an unusual outcome (B. cereus) on an uncommon valve (tricuspid valve).