Chunawala, Zainali

Background: Aspirin is the most frequently used antiplatelet monotherapy for secondary prevention in patients with established ASCVD. Trials comparing monotherapy with a P2Y12i versus aspirin have shown variable results. Methods: Medline, Embase, & Cochrane Central databases were searched to identify RCTs comparing monotherapy with a P2Y12i versus aspirin for secondary prevention in patients with established ASCVD (ischemic stroke, coronary, or peripheral artery disease). The primary outcome of interest was major adverse cardiac events (MACE). Secondary outcomes were myocardial infarction (MI), stroke, all-cause mortality, & major bleeding. The DerSimonian and Laird random-effects model was used to calculate risk ratios (RR) & the corresponding 95% confidence interval (CI). Heterogeneity among studies was assessed using the Higgins I 2 value. Results: 9 eligible RCTs (5 with clopidogrel & 4 with ticagrelor) with 62,336 patients were included in our analyses. Monotherapy with P2Y12i significantly reduced the risk of MACE by 11% (0.89, 95% CI 0.84 - 0.95, I 2 =0), & MI by 19% (0.81, 95% CI 0.71 - 0.92, I 2 =0) as compared with aspirin monotherapy (Figure). There was no significant difference in the risk of stroke (0.85, 95% CI 0.73-1.01), & all-cause mortality (1.01, 95% CI 0.92 - 1.11) between the 2 treatment groups. There was no significant difference in the risk of major bleeding with P2Y12i monotherapy as compared with aspirin (0.97, 95% CI 0.66 - 1.43, I 2 =0). Results were consistent irrespective of the P2Y12i. Conclusion: P2Y12i monotherapy is associated with a significant reduction in atherothrombotic events as compared with aspirin alone without an increased risk of major bleeding.

Background: It is uncertain whether presence of CAD has a prognostic implication in patients (pts) with CLI. We sought to compare the trends and outcomes of pts with CLI based on presence of history of CAD. Methods: Temporal trends in hospitalization for CLI based on history of CAD were determined using the 2000-2018 NIS database. A multivariable regression analyses of outcomes was performed based on the CAD status and revascularization type. Propensity score matching was used to compare outcomes based on type of revascularization. Primary outcome of interest was in-hospital mortality. Results: Among 13,570,000 pts with CLI (41% female, 69% whites, mean age 69 years), 23% had concomitant CAD and 9.6% underwent revascularization (42.6% endovascular & 57.4% surgical). In pts with CLI, there was an increasing trend in the prevalence of CAD (Figure; Panel A). Furthermore, in pts with CLI + CAD, the frequency of endovascular revascularization increased from 15% to 48% while there was a decreasing trend of surgical revascularization (85% to 52%). After multivariate adjustments, CLI + CAD was associated with increased risk of in-hospital mortality (OR: 1.40; CI: 1.32-1.47) & bleeding requiring transfusion (OR: 1.10; CI: 1.06-1.12) than those with CLI without CAD (Figure; Panel B). Among both patients with CLI + CAD & CLI without CAD, endovascular revascularization was associated with lower likelihood of in-hospital mortality (OR: 0.69; CI: 0.63- 0.76 & OR: 0.71; CI: 0.67-0.76) & bleeding requiring transfusion (OR: 0.40; CI: 0.38- 0.43 & OR: 0.44; CI: 0.43- 0.46) than surgical revascularization. Conclusions: Increasing prevalence and poor prognosis of CAD among patients with CLI warrants immediate attention to optimize preventive and treatment strategies.

AbstractBackground and AimsUp to 50% of patients with Parkinson disease have constipation (PD‐C), but the prevalence of defecatory disorders caused by rectoanal dyscoordination in PD‐C is unknown. We aimed to compare anorectal function of patients with PD‐C versus idiopathic chronic constipation (CC).MethodsAnorectal pressures, rectal sensation, and rectal balloon expulsion time (BET) were measured with high‐resolution anorectal manometry (HR‐ARM) in patients with PD‐C and control patients with CC, matched for age and sex.ResultsWe identified 97 patients with PD‐C and 173 control patients. Eighty‐six patients with PD‐C (89%) had early PD, and 39 (40%) had a defecatory disorder, manifest by a prolonged rectal balloon expulsion time (37 patients) or a lower rectoanal pressure difference during evacuation (2 patients). PD‐C patients with a prolonged BET had a greater anal resting pressure (p = 0.02), a lower rectal pressure increment (p = 0.005), greater anal pressure (p = 0.047), and a lower rectoanal pressure difference during evacuation (p < 0.001). Rectal sensory thresholds were greater in patients with abnormal BET.In the multivariate model comparing CC and PD‐C (AUROC = 0.76), PD‐C was associated with a lower anal squeeze increment (odds ratio [OR] for PD‐C, 0.93 [95% CI, 0.91–0.95]), longer squeeze duration (OR, 1.05 [95% CI, 1.03–1.08]), lower rectal pressure increment (OR per 10 mm Hg, 0.72 [95% CI, 0.66–0.79]), and negative rectoanal gradient during evacuation (OR per 10 mm Hg, 1.16 [95% CI, 1.08–1.26]).ConclusionsCompared with CC, PD‐C was characterized by impaired squeeze pressure, longer squeeze duration, lower increase in rectal pressure, and a more negative rectoanal gradient during evacuation.

AbstractBackgroundThe optimal methods for measuring and analyzing anal resting and squeeze pressure with high‐resolution manometry (HRM) are unclear.MethodsAnal resting and squeeze pressures were measured with HRM in 90 healthy women, 35 women with defecatory disorders (DD), and 85 with fecal incontinence (FI). Pressures were analyzed with Manoview™ software and a customized approach. Resting pressures measured for 20, 60, and 300 s were compared. During the squeeze period, (3 maneuvers, 20 s each), the squeeze increment, which was averaged over 5, 10, 15, and 20 s, and squeeze duration were evaluated.ResultsCompared to healthy women, the anal resting pressure, squeeze pressure increment, and squeeze duration were lower in FI (p ≤ 0.04) but not in DD. The 20, 60, and 300 s resting pressures were strongly correlated (concordance correlation coefficients = 0.96–0.99) in healthy and DD women. The 5 s squeeze increment was the greatest; 10, 15, and 20 s values were progressively lower (p < 0.001). The squeeze pressure increment and duration differed (p < 0.01) among the three maneuvers in healthy and DD women but not in FI women. The upper 95th percentile limit for squeeze duration was 19.5 s in controls, 19.9 s in DD, and 19.3 s in FI. Adjusted for age, resting pressure, and squeeze duration, a greater squeeze increment was associated with a lower risk of FI versus health (OR, 0.96; 95% CI, 0.94–0.97).ConclusionsThese findings suggest that anal resting and squeeze pressures can be accurately measured over 20 s. In most patients, one squeeze maneuver is probably sufficient.

Background: Coronary artery disease (CAD) is a common cause of heart failure (HF). Whether the extent of coronary artery stenosis differs by HF type or prognosis for patients admitted with acute decompensated heart failure (ADHF) is uncertain. Methods: The Atherosclerosis Risk in Communities (ARIC) study conducted hospital surveillance of adjudicated HF in 4 US areas from 2005-2014. Medical histories were abstracted from the hospital record. Obstructive CAD was defined as > 49% stenosis in the left main coronary artery or >74% stenosis in the other major coronary arteries. Associations between obstructive CAD and 28-day mortality were analyzed separately for heart failure with preserved ejection fraction (HFpEF) and reduced ejection fraction (HFrEF), adjusting for age, race, sex, year of admission, and coronary revascularization procedures. All analyses were weighted by the inverse of the sampling probability. Results: A total of 5115 patients admitted with ADHF underwent coronary angiography during the hospital visit (mean age = 72, 45% women, 28% Black, 30% HFpEF). Obstructive CAD was more prevalent with HFrEF ( Figure 1 ), whether at the left main coronary artery (16% vs 12%), left anterior descending artery (50% vs 35%), left circumflex artery (42% vs 34%), right coronary artery (45% vs 34%), or multiple coronary vessels (47% vs 34%). A similar proportion of patients with obstructive CAD underwent revascularization, irrespective of HF type (HFrEF: 55%, HFpEF: 61%). After adjustments, obstructive CAD (in any vessel) was associated with higher 28-day mortality, both for HFrEF (OR: 3.21; CI: 1.91 - 5.97) and HFpEF (OR: 3.62; 95% CI: 1.43 - 9.18) with no significant interaction by HF type ( P -interaction = 0.9). Conclusion: Patients hospitalized with ADHF and coexisting obstructive CAD are at greater risk of short-term mortality, irrespective of the HF type, warranting the need for effective interventions as well as secondary preventive measures in this population.

AbstractContextSARS-CoV-2 infects the gastrointestinal tract and may be associated with symptoms that resemble diabetic gastroparesis. Why patients with diabetes who contract COVID-19 are more likely to have severe disease is unknown.ObjectiveWe aimed to compare the duodenal mucosal expression of SARS-CoV-2 and inflammation-related genes in diabetes gastroenteropathy (DGE), functional dyspepsia (FD), and healthy controls.MethodsGastrointestinal transit, and duodenal mucosal mRNA expression of selected genes were compared in 21 controls, 39 DGE patients, and 37 FD patients from a tertiary referral center. Pathway analyses were performed.ResultsPatients had normal, delayed (5 FD [13%] and 13 DGE patients [33%]; P = 0.03 vs controls), or rapid (5 FD [12%] and 5 DGE [12%]) gastric emptying (GE). Compared with control participants, 100 SARS-CoV-2-related genes were increased in DGE (FDR &lt; 0.05) vs 13 genes in FD; 71 of these 100 genes were differentially expressed in DGE vs FD but only 3 between DGE patients with normal vs delayed GE. Upregulated genes in DGE include the SARS-CoV2 viral entry genes CTSL (|Fold change [FC]|=1.16; FDR &lt; 0.05) and CTSB (|FC|=1.24; FDR &lt; 0.05) and selected genes involved in viral replication (eg, EIF2 pathways) and inflammation (CCR2, CXCL2, and LCN2, but not other inflammation-related pathways eg, IL-2 and IL-6 signaling).ConclusionSeveral SARS-CoV-2-related genes were differentially expressed between DGE vs healthy controls and vs FD but not between DGE patients with normal vs delayed GE, suggesting that the differential expression is related to diabetes per se. The upregulation of CTSL and CTSB and replication genes may predispose to SARS-CoV2 infection of the gastrointestinal tract in diabetes.

Abstract Introduction The prevalence and outcomes of polyvascular disease (PVD) in patients admitted with acute decompensated heart failure (ADHF) have not been previously reported, nor is it known whether associations differ for heart failure (HF) with reduced vs. preserved ejection fraction (HFrEF vs HFpEF, respectively). Purpose To investigate the relationship between atherosclerotic involvement of multiple arterial territories and mortality in patients hospitalized with ADHF. Methods The Atherosclerosis Risk in Communities (ARIC) study conducted hospital surveillance of adjudicated heart failure in 4 US areas from 2005–2014, with events verified by physician review. Medical histories were abstracted from the hospital record. PVD was defined by coexisting disease in ≥2 arterial beds, identified by prevalent coronary artery disease, peripheral arterial disease, and cerebrovascular disease. Mortality hazards of PVD vs. no PVD were analyzed separately for HFpEF and HFrEF, with adjustment for age, race, sex, year of admission and geographic region. All analyses were weighted by the inverse of the sampling probability. Results Of 24,936 ADHF hospitalizations (52% female, 32% Black, mean age 75 years), 19% had PVD (22% among HFrEF hospitalizations, 17% among HFpEF hospitalizations), Figure 1. There was an increasing trend in 1-year mortality with 0, 1 and ≥2 arterial bed involvement, both for patients with HFrEF (29% to 32% to 38%; P-trend=0.0006) and HFpEF (26% to 32% to 37%; P-trend &lt;0.0001). After adjustments, PVD was associated with a 20% higher hazard of 1-year mortality in patients with HFrEF (HR=1.23; 95% CI: 1.06–1.44) and a 30% higher hazard in patients with HFpEF (HR=1.33; 95% CI: 1.09–1.63), with no significant interaction by HF type (P-interaction = 0.5). Conclusion Patients hospitalized with ADHF and coexisting PVD have an increased risk of death, irrespective of HF type. Clinical attention should be directed toward PVD, with secondary prevention strategies enacted to improve the prognosis of this vulnerable population. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): National Institutes of Health Distributions of arterial diseaseTrends in 1-year mortality outcomes

Background Acute myocardial infarction (AMI) with in‐hospital onset (AMI‐IHO) has poor prognosis but is clinically underappreciated. Whether its occurrence has changed over time is uncertain. Methods and Results Since 1987, the ARIC (Atherosclerosis Risk in Communities) study has conducted adjudicated surveillance of AMI hospitalizations in 4 US communities. Our analysis was limited to patients aged 35 to 74 years with symptomatic AMI. Patients with symptoms initiating after hospital arrival were considered AMI‐IHO. A total of 26 678 weighted hospitalizations (14 276 unweighted hospitalizations) for symptomatic AMI were identified from 1995 to 2014, with 1137 (4%) classified as in‐hospital onset. The population incidence rate of AMI‐IHO increased in the 4 ARIC communities from 1995 through 2004 to 2005 through 2014 (12.7—16.9 events per 100 000 people; P for 20‐year trend <0.0001), as did the proportion of AMI hospitalizations with in‐hospital onset (3.7%–6.1%; P for 20‐year trend =0.03). The 10‐year proportions were stable for patients aged 35 to 64 years (3.0%–3.4%; P for 20‐year trend =0.3) but increased for patients aged ≥65 years (4.6%–7.8%; P for 20‐year trend =0.008; P for interaction by age group =0.04). AMI‐IHO had a more severe clinical course with lower use of AMI therapies or invasive strategies and higher in‐hospital (7% versus 3%), 28‐day (19% versus 5%), and 1‐year (29% versus 12%) mortality ( P< 0.0001 for all). Conclusions In this population‐based community surveillance, AMI‐IHO increased from 2005 to 2014, particularly among older patients. Quality initiatives to improve recognition and management of AMI‐IHO should be especially focused on hospitalized patients aged >65.