Modified version of the American College of Cardiology's recommendation for low-dose prothrombin complex concentrate is effective for warfarin reversal.

BACKGROUND: Dosing of four factor prothrombin complex concentrate (4PCC) for warfarin reversal remains controversial. Recently, the American College of Cardiology (ACC) recommended a low-dose PCC regimen as an option for warfarin reversal in acute major bleeding. We performed a retrospective study evaluating if a modified version of the ACC guideline recommendations was effective for warfarin reversal in acute major bleeds when compared to traditional variable dosing. METHODS: This was a retrospective cohort study of patients who received 4PCC for warfarin reversal in a 12 month period. We included patients that were ≥18 years of age, received 4PCC for warfarin reversal, and had an initial International Normalized Ratio (INR) of >2. Our primary outcome was the number of patients who had a post-4PCC infusion INR of <1.6. RESULTS: A total of 60 patients were included in the final analysis with 30 patients stratified to the traditional dosing and low-dose groups, respectively. Patient demographics were similar between both groups. We found no difference in the number of patients who had a post-4PCC infusion INR <1.6 between the traditional dosing and low dosing group (90.0% vs. 86.7%; p = 0.68). Additionally, we found no difference between post-infusion median INRs in each group (1.35 vs. 1.30; p = 0.16). Approximately 1000 units per patient were spared when utilizing the low-dose regimen. CONCLUSION: A modified version of the ACC's low-dose 4PCC option for warfarin reversal achieves similar outcomes for lowering INR values compared to traditional variable dosing regimens.

Telemedicine during COVID-19: a survey of Health Care Professionals' perceptions.

The National Health Service (NHS) has rapidly adopted telemedicine solutions as an alternative to face-to-face consultations during the COVID-19 pandemic. The majority of HCPs (Healthcare Professionals) were unfamiliar with Telemedicine prior to the current pandemic. Remote consultation is expected to continue for the foreseeable future, thus we designed this survey. A survey designed to evaluate the use of telephone consultation by HCPs, assessing its implementation, challenges and drawbacks. A web link survey conducted through SurveyMonkey was sent to HCPs across six UK Trusts the period of May 2020. The survey received 114 responses (84%) being doctors. 95% of respondents had not received training prior to engaging in telemedicine consultations. 64% were unaware of the updated General Medical Council guidance concerning remote consultations. The most common barrier in remote consultation was the inability to access patient records raised by 37% of respondents. However, 73% of respondents felt that patients understood their medical condition and the instructions given to them over the phone, and 70% agreed that videoconference consultations would add to patients care. Telemedicine can be used for selected groups of patients in the post COVID-19 era, and the HCPs carrying that should have the sufficient experience and knowledge expected to operate these clinics.

Left ventricular assist device: a bridge to transplant or destination therapy?

Heart failure is a major problem worldwide; it is the leading cause of hospitalisation and is posing a huge financial burden. Advances in healthcare have contributed to increased life expectancy, with a resultant increase in the number of patients with chronic heart failure. For many patients who are still severely symptomatic despite optimal medical therapy and cardiac resynchronisation therapy, cardiac transplantation would be the preferred treatment option. However, hopes are cut short with a limited donor pool of hearts for the increasing number of patients requiring cardiac transplantation. One uprising method to fill this treatment void for patients with advanced end-stage heart failure (ESHF) is the Left Ventricular Assist Device (LVAD). Although traditionally used as a bridge to transplantation, owing to limitation of suitable donors, evidence suggests increasing potential for the use of LVAD as destination therapy (DT), that is, lifelong permanent support. Exploration of DT is a promising avenue to many patients suffering with ESHF who may never be fortunate enough to receive a heart transplant, but not without reservations of its efficacy, safety, effects on quality-adjusted life years and cost-effectiveness, especially in comparison to heart transplantation.

Predictive value of the PRAETORIAN score for defibrillation test success in patients with subcutaneous ICD: A subanalysis of the PRAETORIAN-DFT trial.

BACKGROUND: The PRAETORIAN score estimates the risk of failure of subcutaneous implantable cardioverter-defibrillator (S-ICD) therapy by using generator and lead positioning on bidirectional chest radiographs. The PRospective randomized compArative trial of subcutanEous implanTable cardiOverter-defibrillatoR ImplANtation with and without DeFibrillation Testing (PRAETORIAN-DFT) investigates whether PRAETORIAN score calculation is noninferior to defibrillation testing (DFT) with regard to first shock efficacy in spontaneous events. OBJECTIVE: This prespecified subanalysis assessed the predictive value of the PRAETORIAN score for defibrillation success in induced ventricular arrhythmias. METHODS: This multicenter investigator-initiated trial randomized 965 patients between DFT and PRAETORIAN score calculation after de novo S-ICD implantation. Successful DFT was defined as conversion of induced ventricular arrhythmia in <5 seconds from shock delivery within 2 attempts. Bidirectional chest radiographs were obtained after implantation. The predictive value of the PRAETORIAN score for DFT success was calculated for patients in the DFT arm. RESULTS: In total, 482 patients were randomized to undergo DFT. Of these patients, 457 (95%) underwent DFT according to protocol, of whom 445 (97%) had successful DFT and 12 (3%) had failed DFT. A PRAETORIAN score of ≥90 had a positive predictive value of 25% for failed DFT, and a PRAETORIAN score of <90 had a negative predictive value of 99% for successful DFT. A PRAETORIAN score of ≥90 was the strongest independent predictor for failed DFT (odds ratio 33.77; confidence interval 6.13-279.95; P < .001). CONCLUSION: A PRAETORIAN score of <90 serves as a reliable indicator for DFT success in patients with S-ICD, and a PRAETORIAN score of ≥90 is a strong predictor for DFT failure.

Prevalence of pre-eclampsia and adverse pregnancy outcomes in women with pre-existing cardiomyopathy: a multi-centre retrospective cohort study.

Pre-eclampsia is associated with postnatal cardiac dysfunction; however, the nature of this relationship remains uncertain. This multicentre retrospective cohort study aimed to determine the prevalence of pre-eclampsia in women with pre-existing cardiac dysfunction (left ventricular ejection fraction < 55%) and explore the relationship between pregnancy outcome and pre-pregnancy cardiac phenotype. In this cohort of 282 pregnancies, pre-eclampsia prevalence was not significantly increased (4.6% [95% C.I 2.2-7.0%] vs. population prevalence of 4.6% [95% C.I. 2.7-8.2], p = 0.99); 12/13 women had concurrent obstetric/medical risk factors for pre-eclampsia. The prevalence of preterm pre-eclampsia (< 37 weeks) and fetal growth restriction (FGR) was increased (1.8% vs. 0.7%, p = 0.03; 15.2% vs. 5.5%, p < 0.001, respectively). Neither systolic nor diastolic function correlated with pregnancy outcome. Antenatal ß blockers (n = 116) were associated with lower birthweight Z score (adjusted difference - 0.31 [95% C.I. - 0.61 to - 0.01], p = 0.04). To conclude, this study demonstrated a modest increase in preterm pre-eclampsia and significant increase in FGR in women with pre-existing cardiac dysfunction. Our results do not necessarily support a causal relationship between cardiac dysfunction and pre-eclampsia, especially given the population's background risk status. The mechanism underpinning the relationship between cardiac dysfunction and FGR merits further research but could be influenced by concomitant ß blocker use.

Post-medistinoscopy chylopericardium.

Isolated Chylopericardium (without chylothorax) is a rare clinical disorder that may happen idiopathically or secondary to trauma, radiotherapy, lymphatic anomalies, infections or mediastinal neoplasm. We present a case of middle-aged male with no past medical history of note prior to developing heavy sweating, loss of weight and cough. A series of investigations were done including chest computed tomography which showed enlarged mediastinal lymph nodes leading to uncomplicated mediastinoscopy and lymph node biopsy. Six days after being discharged, he developed dyspnoea and chest pain. Echocardiography revealed massive pericardial effusion. Pericardiocentesis was done and surprisingly revealed milky white chylous fluid. The patient was then successfully managed without the need for further intervention.

The primary prevention implantable cardioverter-defibrillator (ICD) during the COVID-19 pandemic.

During the recent 'first wave' of the COVID-19 pandemic, the National Health Service (NHS) has triaged planned services to create surge capacity. The primary prevention implantable cardioverter-defibrillator (ICD) was in a grey area of triage guidance, but it was suggested as a procedure that could be reasonably stopped. Recent reports have highlighted deaths of patients awaiting ICDs who may have been deferred during the pandemic. In our trust we reorganised our device service and continued to implant primary prevention ICDs during the 'first wave' and, here, report that most patients wished to proceed and underwent uncomplicated implantations. One patient later died from COVID-19, although the transmission site cannot be definitively concluded. With strict adherence to public health guidance and infection prevention strategies, we believe that ICD implantation can be performed safely during the pandemic, and this should be standard practice during subsequent surges.

Intermittent Loss of Telemetry Data: Lessons From a Leadless Pacemaker.

We present the case of a 63-year-old female patient who presented to the pacemaker clinic for a scheduled interrogation of her leadless pacemaker. The device interrogation was suggestive of intermittent under-sensing with failure to pace. Connecting the electrocardiogram lead to the pacing system analyzer raised the suspicion of intermittent loss of telemetry data. (Level of Difficulty: Beginner.).

First experience in quadripolar active fixation coronary sinus lead extraction: a case report.

BACKGROUND: The Attain Stability Quadripolar 4798 lead is a relatively new quadripolar active fixation coronary sinus (CS) lead. No cases of extraction of a chronically implanted 4798 lead have been published to date. CASE SUMMARY: A 52-year-old man with a history of previous cardiac resynchronization therapy pacemaker (CRT-P) insertion and atrioventricular node ablation presented to our institution with a pocket infection 69 weeks after implantation. Directed intravenous antibiotic therapy was commenced and an extraction was performed the following day. Extraction of the right atrial and right ventricular leads was simple and achieved with gentle manual traction. Extraction of the CS lead was more difficult. Significant traction was required due to the formation of adhesions inside the CS but extraction of the lead was eventually successful without complication. Specialized extraction equipment was not required. A new contralateral CRT-P device was implanted, and the patient was discharged home. He remains well at 3 months of follow-up. DISCUSSION: We present the first case of extraction of a chronically implanted active fixation Attain Stability Quadripolar lead. Our experience demonstrates that this has been performed successfully without specialist tools and with preservation of the CS branch. Significant adhesion was noted at the site of active fixation, however. Potential difficulty with this lead's extraction should therefore be considered when contemplating its use.

Synthesis and structure-activity relationships of a novel series of 2,3,5,6,7,9-hexahydrothieno[3,2-b]quinolin-8(4H)-one 1,1-dioxide K(ATP) channel openers: discovery of (-)-(9S)-9-(3-bromo-4-fluorophenyl)-2,3,5,6,7,9- hexahydrothieno[3,2-b]quinolin-8(4H)-one 1,1-dioxide (A-278637), a potent K(ATP) opener that selectively inhibits spontaneous bladder contractions.

Structure-activity relationships were investigated on a novel series of sulfonyldihydropyridine-containing K(ATP) openers. Ring sizes, absolute stereochemistry, and aromatic substitution were evaluated for K(ATP) activity in guinea pig bladder cells using a fluorescence-based membrane potential assay and in a pig bladder strip assay. The inhibition of spontaneous bladder contractions in vitro was also examined for a select group of compounds. All compounds studied showed greater potency to inhibit spontaneous bladder contractions relative to their potencies to inhibit contractions elicited by electrical stimulation. In an anesthetized pig model of myogenic bladder overactivity, compound 14 and (-)-cromakalim 1 were found to inhibit spontaneous bladder contractions in vivo at plasma concentrations lower than those that affected hemodynamic parameters. Compound 14 showed approximately 5-fold greater selectivity than 1 in vivo and supports the concept that bladder-selective K(ATP) channel openers may have utility in the treatment of overactive bladder.

Pharmacological characterization of a 1,4-dihydropyridine analogue, 9-(3,4-dichlorophenyl)-3,3,6,6-tetramethyl-3,4,6,7,9,10-hexahydro-1,8(2H,5H)-acridinedione (A-184209) as a novelK(ATP) channel inhibitor.

1. This study reports on the identification and characterization of a 1,4-dihydropyridine analogue, 9-(3,4-dichlorophenyl)-3,3,6,6-tetramethyl-3,4,6,7,9,10-hexahydro-1,8(2H,5H)-acridinedione (A-184209) as a novel inhibitor of ATP-sensitive K(+) channels. 2. A-184209 inhibited membrane potential changes evoked by the prototypical cyanoguanidine ATP-sensitive K(+) channel opener (KCO) P1075 in both vascular (A10) and urinary bladder smooth muscle cells with IC(50) values of 1.44 and 2.24 micro M respectively. 3. P1075-evoked relaxation of 25 mM K(+) stimulated aortic strips was inhibited by A-184209 in an apparently competitive fashion with a pA(2) value of 6.34. 4. The potencies of A-184209 to inhibit P1075-evoked decreases in membrane potential responses in cardiac myocytes (IC(50)=0.53 micro M) and to inhibit 2-deoxyglucose-evoked cation efflux pancreatic RINm5F cells (IC(50)=0.52 micro M) were comparable to the values for inhibition of smooth muscle K(ATP) channels. 5. On the other hand, a structural analogue of A-184209 that lacked the gem-dimethyl substituent, 9-(3,4-dichlorophenyl)-3,4,6,7,9,10-hexahydro-1,8(2H,5H)-acridinedione (A-184208), was found to be a K(ATP) channel opener, evoking membrane potential responses in A10 smooth muscle cells (EC(50)=385 nM) and relaxing aortic smooth muscle strips (IC(50)=101 nM) in a glyburide-sensitive manner. 6. Radioligand binding studies demonstrated that A-184209 displaced SUR1 binding defined by [(3)H]glyburide binding to RINm5F cell membranes with a K(i) value of 0.11 micro M whereas A-184208 was ineffective. On the other hand, both A-184209 (K(i)=1.34 micro M) and A-184208 (K(i)=1.14 micro M) displaced binding of the KCO radioligand, [(125)I]A-312110 in guinea-pig bladder membranes with similar affinities. 7. These studies demonstrate that A-184209 is a novel and structurally distinct compound that inhibits K(ATP) channels in smooth muscle with potencies comparable to glyburide. The structural overlap between DHP openers and blockers, together with their differential interaction with ligand binding sites, support the notion that both openers and blockers bind to similar or very closely coupled sites on the sulfonylurea receptor and that subtle changes in the pharmacophore itself could switch functional properties from K(ATP) channel activation to inhibition.

A patient with Wegener's granulomatosis in apparent remission presenting with complete atrioventricular block.

Wegener's granulomatosis is a systemic necrotizing granulomatous vasculitis of small- to medium-sized vessels typically affecting upper and lower airways, lungs, and kidneys. Cardiac involvement is less common and conducting tissue involvement is extremely rare. Cardiac manifestations are often not clinically apparent, but are associated with increased mortality. We report the case of a 36-year-old female with Wegener's thought to be in remission, presenting in complete atrioventricular (AV) block, with echocardiographic evidence of basal interatrial septum and basal lateral left atrial wall thickening. Despite immunosuppression therapy a permanent pacemaker was required for recurring complete AV block. Although rare, this case emphasizes the need for careful and regular screening for cardiac involvement in this multi-system condition.