Outcomes of Patients With Takotsubo Syndrome Compared With Type 1 and Type 2 Myocardial Infarction.

Background Takotsubo syndrome (TS) and myocardial infarction (MI) share similar clinical and laboratory characteristics but have important differences in causes, demographics, management, and outcomes. Methods and Results In this observational study, the National Inpatient Sample and National Readmission Database were used to identify patients admitted with TS, type 1 MI, or type 2 MI in the United States between October 1, 2017, and December 31, 2019. We compared patients hospitalized with TS, type 1 MI, and type 2 MI with respect to key features and outcomes. Over the 27-month study period, 2 035 055 patients with type 1 MI, 639 075 patients with type 2 MI, and 43 335 patients with TS were identified. Cardiac arrest, ventricular fibrillation, and ventricular tachycardia were more prevalent in type 1 MI (4.02%, 3.2%, and 7.2%, respectively) compared with both type 2 MI (2.8%, 0.8%, and 5.4% respectively) and TS (2.7%, 1.8%, and 5.3%, respectively). Risk of mortality was lower in TS compared with both type 1 MI (3.3% versus 7.9%; adjusted odds ratio [OR], 0.3; P<0.001) and type 2 MI (3.3% versus 8.2%; adjusted OR, 0.3; P<0.001). Mortality rate (OR, 1.2; P<0.001) and cardiac-cause 30-day readmission rate (adjusted OR, 1.7; P<0.001) were higher in type 1 MI than in type 2 MI. Conclusions Patients with type 1 MI had the highest rates of in-hospital mortality and cardiac-cause 30-day readmission. Risk of all-cause 30-day readmission was highest in patients with type 2 MI. The risk of ventricular arrhythmias in patients with TS is lower than in patients with type 1 MI but higher than in patients with type 2 MI.

Safe and effective delivery of high-power, short-duration radiofrequency ablation lesions with a flexible-tip ablation catheter.

Background: High-power, short-duration (HPSD) radiofrequency ablation (RFA) may reduce ablation time. Concerns that catheter-mounted thermocouples (TCs) can underestimate tissue temperature, resulting in elevated risk of steam pop formation, potentially limit widespread adoption of HPSD ablation. Objective: The purpose of this study was to compare the safety and efficacy of HPSD and low-power, long-duration (LPLD) RFA in the context of pulmonary vein isolation (PVI). Methods: An open-irrigated ablation catheter with a contact force sensor and a flexible-tip electrode containing a TC at its distal end (TactiFlexTM Ablation Catheter, Sensor EnabledTM, Abbott) was used to isolate the left pulmonary veins (PVs) in 12 canines with HPSD RFA (50 W for 10 seconds) and LPLD RFA (30 W for a maximum of 60 seconds). PVI was assessed at 30 minutes and 28 ± 3 days postablation. Computed tomographic scans were performed to assess PV stenosis after RFA. Lesions were evaluated with histopathology. Results: A total of 545 ablations were delivered: 252 with LPLD (0 steam pops) and 293 with HPSD RFA (2 steam pops) (P = .501). Ablation time required to achieve PVI was >3-fold shorter for HPSD than for LPLD RFA (P = .001). All 24 PVs were isolated 30 minutes after ablation, with 12/12 LPLD-ablated and 11/12 HPSD-ablated PVs still isolated at follow-up. Histopathology revealed transmural ablations for HPSD and LPLD RFA. No major adverse events occurred. Conclusion: An investigational ablation catheter effectively delivered RFA lesions. Ablation time required to achieve PVI with HPSD with this catheter was >3-fold shorter than with LPLD RFA.

Outcomes of Patients Hospitalized With Cardiovascular Implantable Electronic Device-Related Infective Endocarditis, Prosthetic Valve Endocarditis, and Native Valve Endocarditis: A Nationwide Study, 2003 to 2017.

Background Most published reports describing outcomes of patients with cardiovascular implantable electronic device-related infective endocarditis (CIED-IE) are single-center studies with small patient sample sizes. The goal of this study was to utilize population-based data to assess trends in CIED-IE hospitalization and to compare outcomes between patients hospitalized with CIED-IE, prosthetic valve endocarditis (PVE), and native valve endocarditis (NVE). Methods and Results A query of the National (Nationwide) Inpatient Sample (NIS) database between 2003 and 2017 identified 646 325 patients hospitalized with infective endocarditis in the United States of whom 585 974 (90%) had NVE, 27 257 (4.2%) had CIED-IE, and 26 111 (4%) had PVE. There was a 509% increase in CIED-IE hospitalizations in the United States from 2003 to 2017 (P trend<0.001). In-hospital mortality and length of stay associated with CIED-IE decreased during the study period from 15% and 20 days in 2003 to 9.7% and 19 days in 2017 (P trend=0.032 and 0.018, respectively). The in-hospital mortality rate was lower in patients hospitalized with CIED-IE (9.2%) than in patients with PVE (12%) and NVE (12%). Length of stay was longest in the CIED-IE group (17 compared with 14 days for both NVE and PVE). Hospital costs were highest for the CIED-IE group ($56 000 compared with $37 000 in NVE and $45 000 in PVE). Conclusions Despite the fact that the number of comorbidities per patient with CIED-IE increased during the study period, mortality rate and hospital length of stay decreased. The mortality rate was significantly lower for patients with CIED-IE than for patients with NVE and PVE. Patients with CIED-IE had the longest lengths of stay and highest hospital costs.

A Practical Guide to Ultrasound-guided Venous Access During Implantation of Pacemakers and Defibrillators.

Ultrasound (US) guidance has been shown to be a safe and effective option for gaining access to the axillary vein during implantation of cardiovascular implantable electronic devices (CIEDs). However, US-based technique has not been universally adopted in CIED implantations performed in cardiac electrophysiology (EP) laboratories, despite potential advantages over other vascular access techniques. For this reason, not all cardiac electrophysiologists have been trained to use US guidance during CIED implantation. This review is intended to provide a practical guide to the use of US guidance to obtain axillary vein access in the EP laboratory setting.

Distinct etiologies of high-sensitivity troponin T elevation predict different mortality risks for patients hospitalized with COVID-19.

BACKGROUND: Cardiovascular events in the context of COVID-19 infection increase the risk of negative patient outcomes, but large cohort studies describing this association are limited. The purpose of the current study was to investigate the potential associations between cardiovascular events and mortality in patients hospitalized due to COVID-19. METHODS: A retrospective chart review was performed in 2450 patients hospitalized for confirmed COVID-19 infection within a single hospital network between March 15 and June 15, 2020. Logistic regression analysis was used to identify predictors of mortality. RESULTS: In the study population, 57% of patients had elevated high sensitivity troponin (hs-TnT) levels. Acute heart failure occurred in 23% of patients and arrhythmias were observed in 8% of patients. Of the 1401 patients with elevated hs-TnT levels, a primary cardiac etiology (e.g., myocardial infarction) was identified in 653 (47%) patients. In the remaining 748 (53%) patients, there was evidence of a primary non-cardiac etiology for hs-TnT elevation such as renal failure (n = 304) and critical illness (n = 286). Elevated hs-TnT was associated with increased risk of mortality. A significantly higher mortality rate was observed for hs-TnT elevation associated with a primary cardiac etiology (OR 4.6, 95% CI: 2.7-7.6; P < 0.001) than a primary non-cardiac etiology (OR 2.7, 95% CI: 1.6-4.5; P < 0.001). CONCLUSIONS: Elevated hs-TnT in the context of COVID-19 infection is associated with a significantly increased mortality risk. Hs-TnT elevation in the context of a primary cardiac etiology confers a nearly 2-fold higher mortality risk than hs-TnT elevation due to a primary non-cardiac etiology.

Global disparities in arrhythmia care: Mind the gap.

Delivery of comprehensive arrhythmia care requires the simultaneous presence of many resources. These include complex hospital infrastructure, expensive implantable equipment, and expert personnel. In many low- and middle-income countries (LMICs), at least 1 of these components is often missing, resulting in a gap between the demand for arrhythmia care and the capacity to supply care. In addition to this treatment gap, there exists a training gap, as many clinicians in LMICs have limited access to formal training in cardiac electrophysiology. Given the progressive increase in the burden of cardiovascular diseases in LMICs, these patient care and clinical training gaps will widen unless further actions are taken to build capacity. Several strategies for building arrhythmia care capacity in LMICs have been described. Medical missions can provide donations of both equipment and clinical expertise but are only intermittently present and therefore are not optimized to provide the longitudinal support needed to create self-sustaining infrastructure. Use of donated or reprocessed equipment (eg, cardiac implantable electronic devices) can reduce procedural costs but does not address the need for infrastructure, including diagnostics and expert personnel. Collaborative efforts involving multiple stakeholders (eg, professional organizations, government agencies, hospitals, and educational institutions) have the potential to provide longitudinal support of both patient care and clinician education in LMICs.

A phase 1 trial of lipid-encapsulated mRNA encoding a monoclonal antibody with neutralizing activity against Chikungunya virus.

Chikungunya virus (CHIKV) infection causes acute disease characterized by fever, rash and arthralgia, which progresses to severe and chronic arthritis in up to 50% of patients. Moreover, CHIKV infection can be fatal in infants or immunocompromised individuals and has no approved therapy or prevention. This phase 1, first-in-human, randomized, placebo-controlled, proof-of-concept trial conducted from January 2019 to June 2020 evaluated the safety and pharmacology of mRNA-1944, a lipid nanoparticle-encapsulated messenger RNA encoding the heavy and light chains of a CHIKV-specific monoclonal neutralizing antibody, CHKV-24 ( NCT03829384 ). The primary outcome was to evaluate the safety and tolerability of escalating doses of mRNA-1944 administered via intravenous infusion in healthy participants aged 18-50 years. The secondary objectives included determination of the pharmacokinetics of mRNA encoding for CHKV-24 immunoglobulin heavy and light chains and ionizable amino lipid component and the pharmacodynamics of mRNA-1944 as assessed by serum concentrations of mRNA encoding for CHKV-24 immunoglobulin G (IgG), plasma concentrations of ionizable amino lipid and serum concentrations of CHKV-24 IgG. Here we report the results of a prespecified interim analysis of 38 healthy participants who received intravenous single doses of mRNA-1944 or placebo at 0.1, 0.3 and 0.6 mg kg-1, or two weekly doses at 0.3 mg kg-1. At 12, 24 and 48 h after single infusions, dose-dependent levels of CHKV-24 IgG with neutralizing activity were observed at titers predicted to be therapeutically relevant concentrations (≥1 µg ml-1) across doses that persisted for ≥16 weeks at 0.3 and 0.6 mg kg-1 (mean t1/2 approximately 69 d). A second 0.3 mg kg-1 dose 1 week after the first increased CHKV-24 IgG levels 1.8-fold. Adverse effects were mild to moderate in severity, did not worsen with a second mRNA-1944 dose and none were serious. To our knowledge, mRNA-1944 is the first mRNA-encoded monoclonal antibody showing in vivo expression and detectable ex vivo neutralizing activity in a clinical trial and may offer a treatment option for CHIKV infection. Further evaluation of the potential therapeutic use of mRNA-1944 in clinical trials for the treatment of CHIKV infection is warranted.

Incidence of carditis and predictors of pacemaker implantation in patients hospitalized with Lyme disease.

BACKGROUND: Lyme carditis, defined as direct infection of cardiac tissue by Borrelia bacteria, affects up to 10% of patients with Lyme disease. The most frequently reported clinical manifestation of Lyme carditis is cardiac conduction system disease. The goal of this study was to identify the incidence and predictors of permanent pacemaker implantation in patients hospitalized with Lyme disease. METHODS: A retrospective cohort analysis of the Nationwide Inpatient sample was performed to identify patients hospitalized with Lyme disease in the US between 2003 and 2014. Patients with Lyme carditis were defined as those hospitalized with Lyme disease who also had cardiac conduction disease, acute myocarditis, or acute pericarditis. Patients who already had pacemaker implants at the time of hospitalization (N = 310) were excluded from the Lyme carditis subgroup. The primary study outcome was permanent pacemaker implantation. Secondary outcomes included temporary cardiac pacing, permanent pacemaker implant, and in-hospital mortality. RESULTS: Of the 96,140 patients hospitalized with Lyme disease during the study period, 10,465 (11%) presented with Lyme carditis. Cardiac conduction system disease was present in 9,729 (93%) of patients with Lyme carditis. Permanent pacemaker implantation was performed in 1,033 patients (1% of all Lyme hospitalizations and 11% of patients with Lyme carditis-associated conduction system disease). Predictors of permanent pacemaker implantation included older age (OR: 1.06 per 1 year; 95% CI:1.05-1.07; P<0.001), complete heart block (OR: 21.5; 95% CI: 12.9-35.7; P<0.001), and sinoatrial node dysfunction (OR: 16.8; 95% CI: 8.7-32.6; P<0.001). In-hospital mortality rate was higher in patients with Lyme carditis (1.5%) than in patients without Lyme carditis (0.5%). CONCLUSIONS: Approximately 11% of patients hospitalized with Lyme disease present with carditis, primarily in the form of cardiac conduction system disease. In this 12-year study, 1% of all hospitalized patients and 11% of those with Lyme-associated cardiac conduction system disease underwent permanent pacemaker implantation.

Management of Atrial Fibrillation in the Emergency Department.

PURPOSE OF REVIEW: Atrial fibrillation (AF) is the most common arrhythmia in adults and is responsible for 600,000 emergency department (ED) visits each year in the USA. Over 60% of these patients are admitted to inpatient units. The prevalence of AF is increasing, resulting in higher numbers of AF-related ED visits and inpatient admissions. These trends underscore the need for improvements in the efficiency of AF management in the ED. RECENT FINDINGS: Several treatment protocols have been developed to address challenges associated with AF management in the ED, including: initiation of oral anticoagulant (OAC) therapy, cardioversion, and arranging for outpatient follow-up. Studies of these protocols have demonstrated that they can be utilized safely and effectively. Published treatment protocols for AF in the ED have been shown to reduce unnecessary hospital admissions and improve adherence to guideline-directed OAC therapy. Widespread adoption of AF treatment protocols could improve patient outcomes and reduce the costs associated with inpatient AF treatment.

MAUDE Database Analysis of Post-Approval Outcomes following Left Atrial Appendage Closure with the Watchman Device.

Left atrial appendage closure (LAAC) is an important strategy to reduce stroke risk in patients with non-valvular atrial fibrillation (AF) who are at high risk of bleeding on long-term anticoagulation. Real-world assessments of the safety of the Watchman LAAC device remain limited. The objective of this study was to determine the frequency and timing of adverse events associated with Watchman LAAC device implants performed after FDA approval. Adverse events associated with Watchman LAAC implants performed between March 2015 and March 2019 were identified through a search of the FDA Manufacturer and User Facility Device Experience (MAUDE) database. During the study period, 3,652 unique adverse events were identified. An estimated 43,802 Watchman implants were performed in the United States during the study period. The overall adverse event rate was 7.3% and the mortality rate was 0.4%. Of the 159 unique types of adverse events identified, pericardial effusion was most common (1.4%). Most adverse events (73%) occurred intraoperatively (59%) or within 1 day of the procedure (15%). However, 19% of deaths, 24% of strokes and 27% of device embolizations occurred >1 month after implantation. The rates of most Watchman-related adverse events reported in the MAUDE database were comparable to those observed in clinical trials. A majority of adverse events occurred within 1 day of implant. In conclusion, while the absolute event rates were low, a significant proportion of device embolizations, strokes, and deaths occurred >1 month after Watchman implant.

Gelatin Methacryloyl Bioadhesive Improves Survival and Reduces Scar Burden in a Mouse Model of Myocardial Infarction.

Background Delivery of hydrogels to the heart is a promising strategy for mitigating the detrimental impact of myocardial infarction (MI). Challenges associated with the in vivo delivery of currently available hydrogels have limited clinical translation of this technology. Gelatin methacryloyl (GelMA) bioadhesive hydrogel could address many of the limitations of available hydrogels. The goal of this proof-of-concept study was to evaluate the cardioprotective potential of GelMA in a mouse model of MI. Methods and Results The physical properties of GelMA bioadhesive hydrogel were optimized in vitro. Impact of GelMA bioadhesive hydrogel on post-MI recovery was then assessed in vivo. In 20 mice, GelMA bioadhesive hydrogel was applied to the epicardial surface of the heart at the time of experimental MI. An additional 20 mice underwent MI but received no GelMA bioadhesive hydrogel. Survival rates were compared for GelMA-treated and untreated mice. Left ventricular function was assessed 3 weeks after experimental MI with transthoracic echocardiography. Left ventricular scar burden was measured with postmortem morphometric analysis. Survival rates at 3 weeks post-MI were 89% for GelMA-treated mice and 50% for untreated mice (P=0.011). Left ventricular contractile function was better in GelMA-treated than untreated mice (fractional shortening 37% versus 26%, P<0.001). Average scar burden in GelMA-treated mice was lower than in untreated mice (6% versus 22%, P=0.017). Conclusions Epicardial GelMA bioadhesive application at the time of experimental MI was performed safely and was associated with significantly improved post-MI survival compared with control animals. In addition, GelMA treatment was associated with significantly better preservation of left ventricular function and reduced scar burden.

Impact of a Multidisciplinary Treatment Pathway for Atrial Fibrillation in the Emergency Department on Hospital Admissions and Length of Stay: Results of a Multi-Center Study.

Background Variability in the management of atrial fibrillation (AF) in the emergency department (ED) leads to avoidable hospital admissions and prolonged length of stay (LOS). In a retrospective single-center study, a multidisciplinary AF treatment pathway was associated with a reduced hospital admission rate and reduced LOS. To assess the applicability of the AF pathway across institutions, we conducted a 2-center study. Methods and Results We performed a prospective, 2-stage study at 2 tertiary care hospitals. During the first stage, AF patients in the ED received routine care. During the second stage, AF patients received care according to the AF pathway. The primary study outcome was hospital admission rate. Secondary outcomes included ED LOS and inpatient LOS. We enrolled 104 consecutive patients in each stage. Patients treated using the AF pathway were admitted to the hospital less frequently than patients who received routine care (15% versus 55%; P<0.001). For admitted patients, average hospital LOS was shorter in the AF pathway cohort than in the routine care cohort (64 versus 105 hours, respectively; P=0.01). There was no significant difference in the average ED LOS between AF pathway and routine care cohorts (14 versus 12 hours, respectively; P=0.32). Conclusions In this prospective 2-stage, 2-center study, utilization of a multidisciplinary AF treatment pathway resulted in a 3.7-fold reduction in admission rate and a 1.6-fold reduction in average hospital LOS for admitted patients. Utilization of the AF pathway was not associated with a significant change in ED LOS.

Patient-Specific Bioinks for 3D Bioprinting of Tissue Engineering Scaffolds.

Bioprinting has emerged as a promising tool in tissue engineering and regenerative medicine. Various 3D printing strategies have been developed to enable bioprinting of various biopolymers and hydrogels. However, the incorporation of biological factors has not been well explored. As the importance of personalized medicine is becoming more clear, the need for the development of bioinks containing autologous/patient-specific biological factors for tissue engineering applications becomes more evident. Platelet-rich plasma (PRP) is used as a patient-specific source of autologous growth factors that can be easily incorporated to hydrogels and printed into 3D constructs. PRP contains a cocktail of growth factors enhancing angiogenesis, stem cell recruitment, and tissue regeneration. Here, the development of an alginate-based bioink that can be printed and crosslinked upon implantation through exposure to native calcium ions is reported. This platform can be used for the controlled release of PRP-associated growth factors which may ultimately enhance vascularization and stem cell migration.

Safety and efficacy of delivering high-power short-duration radiofrequency ablation lesions utilizing a novel temperature sensing technology.

Aims: Delivery of high-power short-duration radiofrequency (RF) ablation lesions is not commonly used, in part because conventional thermocouple (TC) technology underestimates tissue temperature, increasing the risk of steam pop, and thrombus formation. We aimed to test whether utilization of an ablation catheter equipped with a highly accurate novel TC technology could facilitate safe and effective delivery of high-power RF lesions. Methods and results: Adult male Yorkshire swine were used for the study. High-power short-duration ablations (10-s total; 90 W for 4 s followed by 50 W for 6 s) were delivered using an irrigated force sensing catheter, equipped with six miniature TC sensors embedded in the tip electrode shell. Power modulation was automatically performed when the temperature reached 65°C. Ablation parameters were recorded and histopathological analysis was performed to assess lesion formation. One hundred and fourteen RF applications, delivered using the study ablation protocol in the ventricles of eight swine [53 in the right ventricle (RV), 61 in the left ventricle (LV)], were analysed. Average power delivered was 55.4 ± 5.3 W and none of the ablations resulted in a steam pop. Fourteen out of the 114 (12.3%) lesions were transmural. The mean lesion depth was 3.9 ± 1.1 mm for the 100 non-transmural lesions. Similar ablation parameters resulted in bigger impedance drop (11.6 Ω vs. 9.1 Ω, P = 0.009) and deeper lesions in the LV compared with the RV (4.3 ± 1.2 mm vs. 3.3 ± 0.8 mm, P < 0.001). Conclusion: Delivery of high-power short-duration RF energy applications, facilitated by a novel ablation catheter system equipped with advanced TC technology, is feasible, safe, and results in the formation of effective ablation lesions.

Novel automated point collection software facilitates rapid, high-density electroanatomical mapping with multiple catheter types.

INTRODUCTION: Manual, point-by-point electroanatomical mapping requires the operator to directly evaluate each point during map construction. Consequently, point collection can be a slow process. An automated 3D mapping system was developed with the goal of improving key mapping metrics, including map completion time and point density. METHODS: Automated 3D mapping software that includes morphology and cycle length discrimination functions for surface and intracardiac electrograms was developed. In five swine, electroanatomical maps (EAMs) of all four cardiac chambers were generated in sinus rhythm. Four catheters were used: two different four-pole ablation catheters, a 20-pole circular catheter, and a 64-pole basket catheter. Automated and manual 3D mapping were compared for 12 different catheter-chamber combinations (paired sets of 10 maps for most combinations, for a total of 156 maps). RESULTS: Automated 3D mapping produced more than twofold increase in the number of points per map, as compared with manual 3D mapping (P ≤0.007 for all catheter-chamber combinations tested). Automated 3D mapping also reduced map completion time by an average of 29% (P < 0.05 for all comparisons). The amount of manual editing of the maps acquired with automated 3D mapping was minimal. CONCLUSION: Automated 3D mapping with the open-platform mapping software described in this study is significantly faster than manual, point-by-point 3D mapping. This resulted in shorter mapping time and higher point density. The morphology discrimination functions effectively excluded ectopic beats during mapping in sinus rhythm and allowed for rapid mapping of intermittent ventricular ectopic beats.

Rapid computation of single PET scan rest-stress myocardial blood flow parametric images by table look up.

PURPOSE: We have recently reported a method for measuring rest-stress myocardial blood flow (MBF) using a single, relatively short, PET scan session. The method requires two IV tracer injections, one to initiate rest imaging and one at peak stress. We previously validated absolute flow quantitation in ml/min/cc for standard bull's eye, segmental analysis. In this work, we extend the method for fast computation of rest-stress MBF parametric images. METHODS: We provide an analytic solution to the single-scan rest-stress flow model which is then solved using a two-dimensional table lookup method (LM). Simulations were performed to compare the accuracy and precision of the lookup method with the original nonlinear method (NLM). Then the method was applied to 16 single scan rest/stress measurements made in 12 pigs: seven studied after infarction of the left anterior descending artery (LAD) territory, and nine imaged in the native state. Parametric maps of rest and stress MBF as well as maps of left (fLV ) and right (fRV ) ventricular spill-over fractions were generated. Regions of interest (ROIs) for 17 myocardial segments were defined in bull's eye fashion on the parametric maps. The mean of each ROI was then compared to the rest (K1r ) and stress (K1s ) MBF estimates obtained from fitting the 17 regional TACs with the NLM. RESULTS: In simulation, the LM performed as well as the NLM in terms of precision and accuracy. The simulation did not show that bias was introduced by the use of a predefined two-dimensional lookup table. In experimental data, parametric maps demonstrated good statistical quality and the LM was computationally much more efficient than the original NLM. Very good agreement was obtained between the mean MBF calculated on the parametric maps for each of the 17 ROIs and the regional MBF values estimated by the NLM (K1mapLM  = 1.019 × K1ROINLM  + 0.019, R2  = 0.986; mean difference = 0.034 ± 0.036 mL/min/cc). CONCLUSIONS: We developed a table lookup method for fast computation of parametric imaging of rest and stress MBF. Our results show the feasibility of obtaining good quality MBF maps using modest computational resources, thus demonstrating that the method can be applied in a clinical environment to obtain full quantitative MBF information.

Single-scan rest/stress imaging: validation in a porcine model with 18F-Flurpiridaz.

PURPOSE: 18F-labeled myocardial flow agents are becoming available for clinical application but the ∼2 hour half-life of 18F complicates their clinical application for rest-stress measurements. The goal of this work is to evaluate in a pig model a single-scan method which provides quantitative rest-stress blood flow in less than 15 minutes. METHODS: Single-scan rest-stress measurements were made using 18F-Flurpiridaz. Nine scans were performed in healthy pigs and seven scans were performed in injured pigs. A two-injection, single-scan protocol was used in which an adenosine infusion was started 4 minutes after the first injection of 18F-Flurpiridaz and followed either 3 or 6 minutes later by a second radiotracer injection. In two pigs, microsphere flow measurements were made at rest and during stress. Dynamic images were reoriented into the short axis view, and regions of interest (ROIs) for the 17 myocardial segments were defined in bull's eye fashion. PET data were fitted with MGH2, a kinetic model with time varying kinetic parameters, in which blood flow changes abruptly with the introduction of adenosine. Rest and stress myocardial blood flow (MBF) were estimated simultaneously. RESULTS: The first 12-14 minutes of rest-stress PET data were fitted in detail by the MGH2 model, yielding MBF measurement with a mean precision of 0.035 ml/min/cc. Mean myocardial blood flow across pigs was 0.61 ± 0.11 mL/min/cc at rest and 1.06 ± 0.19 mL/min/cc at stress in healthy pigs and 0.36 ± 0.20 mL/min/cc at rest and 0.62 ± 0.24 mL/min/cc at stress in the ischemic area. Good agreement was obtained with microsphere flow measurement (slope = 1.061 ± 0.017, intercept = 0.051 ± 0.017, mean difference 0.096 ± 0.18 ml/min/cc). CONCLUSION: Accurate rest and stress blood flow estimation can be obtained in less than 15 min of PET acquisition. The method is practical and easy to implement suggesting the possibility of clinical translation.

Management of atrial fibrillation in patients taking targeted cancer therapies.

Atrial fibrillation (AF) is frequently observed in patients being treated for cancer and can lead to increased morbidity and mortality in this population. With the use of newer, targeted cancer therapies, several drug-drug interactions have emerged that complicate the use of antiarrhythmic drugs (AADs) in patients with active malignancy. Moreover, specific targeted therapies such as ibrutinib may contribute directly to the development of AF. The decision to pursue systemic anticoagulation can be challenging in patients with malignancy due to a number of factors, including the need for frequent procedures, the presence of malignancy-related risk factors for bleeding, and limited data regarding the safety of the novel oral anticoagulants (NOACs) in cancer patients. This review describes the challenges associated with AF management in patients with cancer and highlights a number of important drug-drug interactions that can impact patient management.