Citations

Background: Multimorbidity is common in atrial fibrillation (AF), particularly among older patients who generally have multiple cardiovascular and non-cardiovascular chronic conditions. However, less is known about the accumulation of chronic conditions in younger patients with AF. Methods: Patients aged <65 with incident AF from 2013-2019 from a 27-county region in the Midwest (N=4907) were matched 1:1 on age (±5 years) and sex to referents from the same community. The index date for the matched pair was the date of first diagnosis of AF. Diagnosis of 20 other chronic conditions was ascertained from 3 years prior to index through 12/31/2022. Mean cumulative function curves were used to visualize the accumulation of conditions; Andersen-Gill models estimated associations between AF/referent status and accumulation of conditions. Results: The mean age was 55 years for both patients with AF and matched referents; 71% were male. In the 3 years leading up to AF diagnosis, only 4% of patients with AF had no additional chronic conditions and 69% had ≥3 chronic conditions. In contrast, 35% of referents had 0 and 32% had ≥3 chronic conditions. The accumulation of chronic conditions was accelerated in patients with AF compared to referents prior to AF diagnosis/index (Figure). After index, patients with AF had increased accumulation of chronic conditions (HR (95% CI): 1.93 (1.71-2.20), 1.82 (1.62-2.05), 1.68 (1.55-1.83), and 1.53 (1.44-1.64) for ages <50, 50-54, 55-59, and 60-64 years, respectively). After 1 year, the differences were attenuated in all age groups with no difference observed between patients with AF and referents in the oldest age group (1.26 (1.08-1.46), 1.28 (1.11-1.47), 1.13 (1.02-1.24), and 1.05 (0.97-1.13) for ages <50, 50-54, 55-59, and 60-64 years). Conclusion: Patients <65 years with AF have an increased accumulation of chronic conditions compared to those without AF, in particular prior to their AF diagnosis and within the first year after AF diagnosis.

Introduction: Obesity and hypertension (HTN) are highly prevalent comorbid risk factors for heart failure with preserved ejection fraction (HFpEF). Obesity and HTN independently increase sympathetic nervous activity and impair muscle blood flow during exercise. Previous work has reported attenuated limb blood flow in patients with HFpEF; however, these findings were compared to controls with dissimilar comorbidities and during small muscle mass exercise. It is unclear if HFpEF alters muscle blood flow responses independent of the obesity- and HTN-mediated alterations. Hypothesis: We hypothesized the muscle blood flow response during cycling would be lower in HFpEF patients than age, sex, BMI, and HTN matched controls (CTL). Methods: HFpEF patients (n=14, 9M/5W, 71±7yrs, 32±4 kg/m 2 ) and CTL (n=12, 8M/4W, 69±7yrs, 31±4 kg/m 2 ) performed an incremental cycling test. Blood pressure was measured by manual sphygmomanometry, cardiac output (Q) by open-circuit acetylene wash-in technique, and systemic vascular resistance (SVR) was calculated. Vastus lateralis blood flow index (BFI) was measured by near-infrared spectroscopy and indocyanine green dye injections and venous norepinephrine concentration was measured. Changes from rest to 40 W of the incremental test are reported. Results: Resting Q, mean arterial pressure, SVR, and venous norepinephrine concentration were not statistically different between groups (p>0.18). From rest to 40 W, the increases in Q (CTL: 3.9±0.8 vs. HFpEF: 3.6±0.7 L/min), mean arterial pressure (CTL: 5.7±2.7 vs. HFpEF: 6.6±6.1 mmHg), and SVR (CTL: -7.3±2.1 vs. HFpEF: -6.0±2.0 mmHg/L/min) were not statistically different between groups (all, p>0.13). The HFpEF group had smaller increases in vastus lateralis BFI at 40 W compared to CTL (CTL: 7.2±3.6 vs. HFpEF: 4.2±2.6 fold-increase from rest) (p=0.02). The HFpEF group had greater increases in venous norepinephrine concentration from rest to 40 W than CTL (CTL: 164±216 vs. HFpEF: 377±247 pg/mL) (p=0.05). Conclusions: Our findings suggest that, compared to age, sex, BMI, and HTN matched controls, patients with HFpEF have an impaired locomotor muscle blood flow response during submaximal cycling exercise likely due to higher locomotor muscle vascular resistance.

Introduction: Prognostic markers and biological pathways linked to detrimental clinical outcomes in heart failure with preserved ejection fraction (HFpEF) remain incompletely defined. Goal: To identify serum proteins associated with risk for HF hospitalization (HFH) and cardiovascular (CV) death in patients with HFpEF, including proteins with differential associations with clinical outcomes in HFpEF compared to HFrEF. Methods: We measured serum levels of 4123 unique proteins in 1117 patients with HFpEF in the PARAGON-HF trial using a modified aptamer proteomic assay. Baseline protein concentrations significantly associated with total HFH and CV death were identified by recurrent events regression, accounting for multiple testing, adjusted for age, sex, treatment, and anticoagulant use, and compared to 2515 patients with HFrEF from the PARADIGM-HF and ATMOSPHERE trials. Results: We identified 288 proteins to be robustly associated with the risk of HFH and CV death (335 events over an average of 2.7 years of follow-up) in a HFpEF trial population. Proteins most strongly related to HFpEF outcomes included B2M, TIMP1, SERPINA4, and SVEP1 ( Figure ). Protein-outcome associations in patients with HFpEF did not markedly differ compared to HFrEF. Just 3 proteins (APOE, RTF1, and VWF) were differentially associated with outcomes between the HF subtypes (FDR <0.05). A proteomic risk score derived in HFpEF patients was not superior to a previous proteomic score derived in HFrEF nor to clinical risk factors, NT-proBNP, or high-sensitivity cardiac troponin. Conclusions: Numerous serum proteins linked to metabolic, coagulation, and extracellular matrix regulatory pathways were associated with worse HFpEF prognosis. SVEP1, a cell adhesion protein recently identified as a HFrEF prognosis biomarker, also strongly predicted risk in HFpEF. Our results demonstrate substantial similarities in serum proteomic risk markers across the EF spectrum.

Introduction: Fontan pathway obstruction is a serious complication characterized by an anatomical or functional narrowing anywhere in the cavo-pulmonary pathways. Here we report the first case where an innovative Fontan conduit rehabilitation procedure with intravascular lithotripsy was used achieving a significant increase in the pathway size. Case: A 28-year-old male with tricuspid atresia status-post Fontan palliation (age 23 months) with bare metal stent implant to treat obstruction at age 15, presented with syncope, ascites and varicose veins. Imaging studies revealed a cirrhotic liver morphology and Fontan pathway obstruction with minimal diameter of 12 mm. Cardiac catheterization confirmed severe Fontan conduit obstruction in addition to LPA stenosis. Serial covered Cheatham-Platinum stents were implanted for conduit coverage followed by Palmaz stents. Non-compliant Atlas balloon dilation to 20 atm was performed without expansion of the Fontan pathway beyond 12 mm due to severe calcification. A 7.0 x 60 mm shock-wave lithotripsy balloon was added alongside the Atlas balloon to modulate the heavily calcified wall with subsequent expansion of the conduit to 21 mm after inflating the Atlas balloon to 14 atm. Discussion: Several studies demonstrated that transcatheter stenting of stenotic Fontan conduits can be safely performed. Intravascular lithotripsy has emerged as a novel therapy for the treatment of coronary vascular calcification. We report the first case of an innovative percutaneous Fontan conduit rehabilitation procedure using a lithotripsy shock wave balloon in an adult with severely calcified Fontan pathway obstruction and prior stents, achieving a 75% increase in the pathway size without significant complications. Further studies are needed to evaluate the long-term safety and efficacy of this novel approach, but this case presents an exciting option for future directions in the percutaneous treatment of Fontan pathway obstruction.

AbstractBackgroundFood intake is regulated by homeostatic and hedonic systems that interact in a complex neuro‐hormonal network. Dysregulation in energy intake can lead to obesity (OB) or anorexia nervosa (AN). However, little is known about the neurohormonal response patterns to food intake in normal weight (NW), OB, and AN.Material & MethodsDuring an ad libitum nutrient drink (Ensure®) test (NDT), participants underwent three pseudo‐continuous arterial spin labeling (pCASL) MRI scans. The first scan was performed before starting the NDT after a > 12 h overnight fast (Hunger), the second after reaching maximal fullness (Satiation), and the third 30‐min after satiation (postprandial fullness). We measured blood levels of ghrelin, cholecystokinin (CCK), glucagon‐like peptide (GLP‐1), and peptide YY (PYY) with every pCASL‐MRI scan. Semiquantitative cerebral blood flow (CBF) maps in mL/100 gr brain/min were calculated and normalized (nCBF) with the CBF in the frontoparietal white matter. The hypothalamus (HT), nucleus accumbens [NAc] and dorsal striatum [DS] were selected as regions of interest (ROIs).ResultsA total of 53 participants, 7 with AN, 17 with NW (body‐mass index [BMI] 18.5–24.9 kg/m2), and 29 with OB (BMI ≥30 kg/m2) completed the study. The NW group had a progressive decrease in all five ROIs during the three stages of food intake (hunger, satiation, and post‐prandial fullness). In contrast, participants with OB showed a minimal change from hunger to postprandial fullness in all five ROIs. The AN group had a sustained nCBF in the HT and DS, from hunger to satiation, with a subsequent decrease in nCBF from satiation to postprandial fullness. All three groups had similar hormonal response patterns with a decrease in ghrelin, an increase in GLP‐1 and PYY, and no change in CCK.ConclusionConditions of regulated (NW) and dysregulated (OB and AN) energy intake are associated with distinctive neurohormonal activity patterns in response to hunger, satiation, and postprandial fullness.

Abstract Iliopsoas tendinitis following total hip arthroplasty has been linked to retroverted acetabular cup position with associated anterior overhang. For severely malpositioned components, preferred treatment is in the form of revision arthroplasty. However, for a substantial number of cases, iliopsoas tendinitis as well as associated pain and disability are observed in the presence of modest acetabular overhang. In such cases, patients may benefit substantially from arthroscopic iliopsoas fractional lengthening. Given altered postarthroplasty anatomy, we present an arthroscopic approach employing an iliopsoas air bursogram. In such a way, safe and predictable access can be provided for efficient tendon lengthening without capsular violation or inadvertent instrumentation of the nearby medial neurovascular bundle. Technique Video video See video under supplementary data.

A 70-year-old male without prior psychiatric history presented with recurrent episodes (<60 seconds each, every 5-10 minutes) of left hemibody and right lower extremity jerking movements concerning for seizure with preserved awareness (Video). Examination showed left hemiparesis (leg > arm) in addition to right lower extremity weakness. Computed tomography showed a right parafalcine acute subdural hematoma (SDH). Clinical events did not recur after intravenous lorazepam (4 mg) and levetiracetam load (3500 mg), and his weakness improved. He was continued on levetiracetam and has since remained seizure free for 16 months. A 60-minute awake/sleep electroencephalogram (EEG) obtained 12 hours after administration of antiseizure medications showed low amplitude theta slowing (posterior predominant) in the range of 5-7 Hz. There was no apparent epileptiform activity or other abnormalities during the awake and sleep recording or photic stimulation. Focal seizures originate from pathologic disruption of neuronal activity within an isolated brain region, almost exclusively from a single hemisphere. Focal seizures may generalize bilaterally with associated impaired awareness. This is the first visual report demonstrating focal, bihemispheric clinical seizures, without generalization or impaired awareness. Rarely patients with generalized motor involvement from seizures have had retained consciousness and memory. The parafalcine SDH likely promoted epileptogenicity of the bilateral hemispheres. Acute and chronic SDH commonly present with seizures. Although there were no supportive electrographic findings, parasagittal epileptogenic lesions may be difficult for both clinical and electrographic localization. Post-event paresis with clinical improvement in the hours after event cessation supports clinical seizure.

AbstractStudy ObjectiveTo develop and validate a model for predicting acute kidney injury (AKI) after high‐dose methotrexate (HDMTX) exposure.DesignRetrospective analysis.SettingMultisite integrated health system throughout Minnesota and Wisconsin.PatientsAdult patients with lymphoma who received HDMTX as a 4‐h infusion.Measurements and Main ResultsLASSO methodology was used to identify factors available at the outset of therapy that predicted incident AKI within 7 days following HDMTX. The model was then validated in an independent cohort. The incidence of AKI within 7 days following HDMTX was 21.6% (95% confidence interval (CI) 18.4%‐24.8%) in the derivation cohort (435 unique patients who received a total of 1642 doses of HDMTX) and 15.6% (95% CI 5.3%‐24.8%) in the validation cohort (55 unique patients who received a total of 247 doses of HDMTX). Factors significantly associated with AKI after HDMTX in the multivariable model included age ≥ 55 years, male sex, and lower HDMTX dose number. Other factors that were not found to be significantly associated with AKI on multivariable analysis, but were included in the final model, were body surface area, Charlson Comorbidity Index, and estimated glomerular filtration rate. The c‐statistic of the model was 0.72 (95% CI 0.69‐0.75) in the derivation cohort and 0.72 (95% CI 0.60‐0.84) in the validation cohort.ConclusionThis model utilizing identified sociodemographic and clinical factors is predictive of AKI following HDMTX administration in adult patients with lymphoma.