Magnetic Resonance Imaging in Pediatric Myocarditis: Trends and Associations With Cost and Outcome

BackgroundCardiac magnetic resonance (CMR) provides tissue characterization and structural and functional data. CMR has high sensitivity and specificity for myocarditis in adults and children. The relationship between pediatric CMR use, cost, and clinical outcome has not been studied.ObjectivesThis work aims to describe temporal trends in CMR imaging for pediatric myocarditis and examine associations between CMR use, hospital cost, and outcomes.MethodsA retrospective cohort study of all inpatients <21 years of age with a diagnosis of myocarditis reported to the Pediatric Health Information System (2004-2019) was performed. Trends in CMR use were examined. A propensity-matched subcohort using center and patient level variables was used to assess whether outcomes differed by CMR use.ResultsA total of 4,195 children with myocarditis from 47 hospitals were identified. The median age was 11.5 years (IQR: 1.5-16.0 years) and 2,617 (62%) were male. CMR was used in 23% and mortality occurred in 6%. CMR use during hospitalization increased from 2% in 2004 to 37% in 2019 (odds ratio [OR]: 1.19 [95% CI: 1.17-1.21]). After propensity score matching, CMR use was associated with higher median cost (+$5,340 [95% CI: +$1,739 to +$9,936]) and similar median length of stay (0 days [95% CI: ?1 to +1 days]). Using quantile regression, CMR was associated with lower 90th percentile cost (?$77,200 [95% CI: ?$127,373 to ?$31,339]). More children receiving CMR were discharged alive in the first 30 days after admission (OR: 1.89 days [95% CI: 1.28-2.29]). Within the propensity matched cohort, <10 of 790 CMR recipients died compared to 42 of 790 in the non-CMR group.ConclusionsCMR use in children with myocarditis has increased over the past 15 years. CMR use is associated with higher cost of hospitalization and similar length of stay for most children but lower cost among the sickest children. CMR use in specific patients may improve clinical outcomes at a lower cost.     

Prognostic Impact of High-Sensitivity C-Reactive Protein in Patients Undergoing Percutaneous Coronary Intervention According to BMI

ObjectivesThe aim of this study was to determine the prevalence and prognostic implications of elevated high-sensitivity C-reactive protein (hsCRP) in patients undergoing percutaneous coronary intervention (PCI) according to body mass index (BMI).BackgroundWhereas elevated hsCRP predicts adverse clinical outcome after PCI in the general population, the impact of BMI on its prognostic utility remains unclear.MethodsData from 14,140 patients who underwent PCI between January 2009 and June 2017 at a large tertiary care center were analyzed. Patients were divided into 4 BMI categories: normal (BMI 18.5 to <25 kg/m², n = 2,808), overweight (BMI 25 to <30 kg/m², n = 6,015), obese (BMI 30 to <35 kg/m², n = 3,490), and severely obese (BMI ≥35 kg/m², n = 1,827). Elevated hsCRP was defined as >3 mg/l. The primary endpoint of interest was the occurrence of major adverse cardiac events (MACE; defined as death, myocardial infarction, or target vessel revascularization) within 1 year after PCI.ResultsElevated hsCRP was present in 18.9%, 23.6%, 33.3%, and 47.7% of the normal, overweight, obese, and severely obese groups, respectively. MACE rates were consistently higher in patients with elevated hsCRP across all BMI categories (normal, 13.4% vs. 8.3%; overweight, 11.2% vs. 7.2%; obese, 10.6% vs. 7.5%; severely obese, 11.9% vs. 6.5%; p < 0.01 for all). After multivariate adjustment, hsCRP elevation remained significantly associated with MACE independent of BMI (hazard ratios: normal, 1.43 [95% confidence interval: 1.04 to 1.95]; overweight, 1.56 [95% confidence interval: 1.21 to 1.88]; obese, 1.40 [95% confidence interval: 1.06 to 1.84]; severely obese, 1.92 [95% confidence interval: 1.35 to 2.75]; p < 0.05 for all).ConclusionsAmong patients undergoing PCI, the prevalence of hsCRP elevation progressively increased with higher BMI. Measurement of hsCRP facilitates prognostic risk assessment for adverse outcome after PCI across a broad range of BMI.     

Downstream Cascades of Care Following High-Sensitivity Troponin Test Implementation

BackgroundPatients with chest pain are often evaluated for acute myocardial infarction through troponin testing, which may prompt downstream services (cascades) of uncertain value.ObjectivesThis study sought to determine the association of high-sensitivity cardiac troponin (hs-cTn) assay implementation with cascade events.MethodsUsing electronic health record and billing data, this study examined patient-visits to 5 emergency departments from April 1, 2017, to April 1, 2019. Difference-in-differences analysis compared patient-visits for chest pain (n = 7,564) to patient-visits for other symptoms (n = 100,415) (irrespective of troponin testing) before and after hs-cTn assay implementation. Outcomes included presence of any cascade event potentially associated with an initial hs-cTn test (primary), individual cascade events, length of stay, and spending on cardiac services.ResultsFollowing hs-cTn implementation, patients with chest pain had a 2.8% (95% confidence interval [CI]: 0.72% to 4.9%) net increase in experiencing any cascade event. They were more likely to have multiple troponin tests (10.5%; 95% CI: 9.0% to 12.0%) and electrocardiograms (7.1 per 100 patient-visits; 95% CI: 1.8 to 12.4). However, they received net fewer computed tomography scans (?1.5 per 100 patient-visits; 95% CI: ?1.8 to ?1.1), stress tests (?5.9 per 100 patient-visits; 95% CI: ?6.5 to ?5.3), and percutaneous coronary intervention (PCI) (?0.65 per 100 patient-visits; 95% CI: ?1.01 to ?0.30) and were less likely to receive cardiac medications, undergo cardiology evaluation (?3.5%; 95% CI: ?4.5% to 2.6%), or be hospitalized (?5.8%; 95% CI: ?7.7% to ?3.8%). Patients with chest pain had lower net mean length of stay (?0.24 days; 95% CI: ?0.32 to ?0.16) but no net change in spending.ConclusionsHs-cTn assay implementation was associated with more net upfront tests yet fewer net stress tests, PCI, cardiology evaluations, and hospital admissions in patients with chest pain relative to patients with other symptoms.     

Effects of Diet and Sodium Reduction on Cardiac Injury,Strain, and Inflammation: The DASH-Sodium Trial

BackgroundThe DASH (Dietary Approaches to Stop Hypertension) diet has been determined to have beneficial effects on cardiac biomarkers. The effects of sodium reduction on cardiac biomarkers, alone or combined with the DASH diet, are unknown.ObjectivesThe purpose of this study was to determine the effects of sodium reduction and the DASH diet, alone or combined, on biomarkers of cardiac injury, strain, and inflammation.MethodsDASH-Sodium was a controlled feeding study in adults with systolic blood pressure (BP) 120 to 159 mm Hg and diastolic BP 80 to 95 mm Hg, randomly assigned to the DASH diet or a control diet. On their assigned diet, participants consumed each of three sodium levels for 4 weeks. Body weight was kept constant. At the 2,100 kcal level, the 3 sodium levels were low (50 mmol/day), medium (100 mmol/day), and high (150 mmol/day). Outcomes were 3 cardiac biomarkers: high-sensitivity cardiac troponin I (hs-cTnI) (measure of cardiac injury), N-terminal pro–B-type natriuretic peptide (NT-proBNP) (measure of strain), and high-sensitivity C-reactive protein (hs-CRP) (measure of inflammation), collected at baseline and at the end of each feeding period.ResultsOf the original 412 participants, the mean age was 48 years; 56% were women, and 56% were Black. Mean baseline systolic/diastolic BP was 135/86 mm Hg. DASH (vs. control) reduced hs-cTnI by 18% (95% confidence interval [CI]: ?27% to ?7%) and hs-CRP by 13% (95% CI: ?24% to ?1%), but not NT-proBNP. In contrast, lowering sodium from high to low levels reduced NT-proBNP independently of diet (19%; 95% CI: ?24% to ?14%), but did not alter hs-cTnI and mildly increased hs-CRP (9%; 95% CI: 0.4% to 18%). Combining DASH with sodium reduction lowered hs-cTnI by 20% (95% CI: ?31% to ?7%) and NT-proBNP by 23% (95% CI: ?32% to ?12%), whereas hs-CRP was not significantly changed (?7%; 95% CI: ?22% to 9%) compared with the high sodium-control diet.ConclusionsCombining a DASH dietary pattern with sodium reduction can lower 2 distinct mechanisms of subclinical cardiac damage: injury and strain, whereas DASH alone reduced inflammation. (Dietary Patterns, Sodium Intake and Blood Pressure [DASH – Sodium]; NCT00000608)     

Reduction in CMR Derived Extracellular Volume With Patisiran Indicates Cardiac Amyloid Regression

ObjectivesThe purpose of this study was to determine the effect of patisiran on the cardiac amyloid load as measured by cardiac magnetic resonance and extracellular volume (ECV) mapping in cases of transthyretin cardiomyopathy (ATTR-CM).BackgroundAdministration of patisiran, a TTR-specific small interfering RNA (siRNA), has been shown to benefit neuropathy in patients with hereditary ATTR amyloidosis, but its effect on ATTR-CM remains uncertain.MethodsPatisiran was administered to 16 patients with hereditary ATTR-CM who underwent assessment protocols at the UK National Amyloidosis Centre. Twelve of those patients concomitantly received diflunisal as a “TTR-stabilizing” drug. Patients underwent serial monitoring using cardiac magnetic resonance, echocardiography, cardiac biomarkers, bone scintigraphy, and 6-min walk tests (6MWTs). Findings of amyloid types and extracellular volumes were compared with those of 16 patients who were retrospectively matched based on cardiac magnetic resonance results.ResultsPatisiran was well tolerated. Median serum TTR knockdown among treated patients was 86% (interquartile range [IQR]: 82% to 90%). A total of 82% of cases showed >80% knockdown. Patisiran therapy was typically associated with a reduction in ECV (adjusted mean difference between groups: ?6.2% [95% confidence interval [CI]: ?9.5% to ?3.0%]; p = 0.001) accompanied by a fall in N-terminal pro–B-type natriuretic peptide concentrations (adjusted mean difference between groups: ?1,342 ng/l [95% CI: ?2,364 to ?322]; p = 0.012); an increase in 6MWT distances (adjusted mean differences between groups: 169 m [95% CI: 57 to 2,80]; p = 0.004) after 12 months of therapy; and a median reduction in cardiac uptake by bone scintigraphy of 19.6% (IQR: 9.8% to 27.1%).ConclusionsReductions in ECV by cardiac magnetic resonance provided evidence for ATTR cardiac amyloid regression in a proportion of patients receiving patisiran.     

Pooled Patient-Level Analysis of Inclisiran Trials in Patients With Familial Hypercholesterolemia or Atherosclerosis

BackgroundInclisiran is a double-stranded small interfering RNA that suppresses proprotein convertase subtilisin–kexin type 9 (PCSK9) translation in the liver, leading to sustained reductions in low-density lipoprotein cholesterol (LDL-C) and other atherogenic lipoproteins with twice-yearly dosing.ObjectivesThe purpose of this study was to conduct a patient-level pooled analysis from 3 phase 3 studies of inclisiran.MethodsParticipants with heterozygous familial hypercholesterolemia (ORION-9 [Trial to Evaluate the Effect of Inclisiran Treatment on Low Density Lipoprotein Cholesterol (LDL-C) in Subjects With Heterozygous Familial Hypercholesterolemia (HeFH)]), atherosclerotic cardiovascular disease (ASCVD) (ORION-10 [Inclisiran for Participants With Atherosclerotic Cardiovascular Disease and Elevated Low-density Lipoprotein Cholesterol]), or ASCVD and ASCVD risk equivalents (ORION-11 [Inclisiran for Subjects With ASCVD or ASCVD-Risk Equivalents and Elevated Low-density Lipoprotein Cholesterol]) taking maximally tolerated statin therapy, with or without other LDL-C–lowering agents, were randomly assigned in a 1:1 ratio to receive either inclisiran or placebo, administered by subcutaneous injection on day 1, day 90, and every 6 months thereafter for 540 days. The coprimary endpoints were the placebo-corrected percentage change in LDL-C level from baseline to day 510 and the time-adjusted percentage change in LDL-C level from baseline after day 90 to day 540. Levels of other atherogenic lipoproteins and treatment-emergent adverse events were also assessed.ResultsA total of 3,660 participants (n = 482, n = 1,561, and n = 1,617 from ORION-9, -10, and -11, respectively) underwent randomization. The placebo-corrected change in LDL-C with inclisiran at day 510 was ?50.7% (95% confidence interval: ?52.9% to ?48.4%; p < 0.0001). The corresponding time-adjusted change in LDL-C was ?50.5% (95% confidence interval: ?52.1% to ?48.9%; p < 0.0001). Safety was similar in both groups. Treatment-emergent adverse events at the injection site were more frequent with inclisiran than placebo (5.0% vs. 0.7%), but were predominantly mild, and none were severe or persistent. Liver and kidney function tests, creatine kinase values, and platelet counts did not differ between groups.ConclusionsThese pooled safety and efficacy data show that inclisiran, given twice yearly in addition to maximally tolerated statin therapy with or without other LDL-C lowering agents, is an effective, safe, and well-tolerated treatment to lower LDL-C in adults with heterozygous familial hypercholesterolemia, ASCVD, or ASCVD risk equivalents.     

Dose-dependent efficacy and safety of licogliflozin on obese adults: A systematic review and meta-analysis of randomized controlled trials

Background and aimLicogliflozin is a dual SGLT1/2 inhibitor acting on the intestine and kidney by reducing glycemic and calorie content. We aimed to determine the efficacy and safety of licogliflozin on Anthropometric measurements and cardiometabolic parameters in obese participants.MethodsWe systematically searched the PubMed, Cochrane Library, Scopus, and Web of Science databases for randomized controlled trials (RCTs) relevant to our eligibility criteria. We performed a subgroup analysis based on licogliflozin doses and the diabetic state of participants. This meta-analysis was registered on PROSPERO (CRD42021286936).ResultsWe identified five RCTs with a total of 905 obese and overweight participants. All participants had a weight reduction of 2.43 kg (95% CI: ?3.17 to ?1.69, p < 0.00001) compared with placebo. The mean difference in HbA1c of obese diabetic patients was (MD: ?0.30%; 95% CI: ?0.45, ?0.16); I2 = 46% in favor of licogliflozin. The incidence of serious adverse events, all-cause mortality, headache, nausea, and vomiting were similar between licogliflozin and placebo (p = 0.72, 0.97, 0.09, 0.53, and 0.89, respectively). However, there was a higher incidence of diarrhea in the licogliflozin group.ConclusionWe found that licogliflozin was safe and tolerable. It reduces body weight significantly. Moreover, it improves glycemic control and other cardiometabolic parameters.     

Left Ventricular Remodeling After Transcatheter Mitral Valve Replacement With Tendyne: New Insights From Computed Tomography

ObjectivesThe aim of this study was to describe the anatomic and functional changes in left-sided chambers using computed tomographic angiography (CTA) from baseline to 1 month after transcatheter mitral valve replacement (TMVR) with the Tendyne prosthesis.BackgroundData on changes in left atrial and left ventricular (LV) volumes after TMVR implantation are very limited.MethodsPatients who underwent TMVR with the Tendyne prosthesis between 2015 and 2018 were analyzed. Changes in LV end-diastolic volume, ejection fraction, LV mass, left atrial volume, and global longitudinal strain were assessed at baseline and 1 month after TMVR using CTA. Specific Tendyne implant characteristics were identified and correlated with remodeling changes.ResultsA total of 36 patients (median age 74 years; interquartile range [IQR]: 69 to 78 years; 78% men; 86% with secondary mitral regurgitation) were included in this study. There were significant decreases in LV end-diastolic volume (281 ml [IQR: 210 to 317 ml] vs. 239 ml [IQR: 195 to 291 ml]; p < 0.001), LV ejection fraction (37% [IQR: 31% to 48%] vs. 30% [IQR: 23% to 40%]; p < 0.001), LV mass (126 g [IQR: 96 to 155 g] vs. 116 g [IQR: 92 to 140 g]; p < 0.001), left atrial volume (171 ml [IQR: 133 to 216 ml] vs. 159 ml [IQR: 125 to 201 ml]; p = 0.027), and global longitudinal strain (−11% [IQR: −17% to −8%] vs. −9% [IQR: −12% to −6%]; p < 0.001) from baseline to 1-month follow-up. Favorable LV end-diastolic volume reverse remodeling occurred in the majority (30 of 36 patients [83%]). Closer proximity of the Tendyne apical pad to the true apex (24 mm [IQR: 21 to 29 mm] vs. 35 mm [IQR: 26 to 40 mm]) was predictive of favorable remodeling (p = 0.037).ConclusionsTMVR with Tendyne results in favorable left-sided chamber remodeling in the majority of patients treated, as detected on CTA at 1 month after implantation. CTA identifies favorable post-TMVR changes, which could be related to specific characteristics of the device implantation.     

Pancreatic exocrine insufficiency is a risk factor for kidney stones in patients with chronic pancreatitis

IntroductionMost patients with chronic pancreatitis (CP) develop pancreatic exocrine insufficiency (PEI) over the course of the disease. PEI may lead to hyperoxaluria and development of urinary oxalate stones. It has been postulated that the patients with CP may be at increased risk of kidney stone formation, but the data is scarce. We aimed to estimate incidence and risk factors for nephrolithiasis in a Swedish cohort of patients with CP.Patients and methodsWe performed retrospective analysis of an electronical medical database of patients diagnosed with definite CP during 2003–2020. We excluded patients <18 years of age, those with missing relevant data in medical charts, patients with probable CP (according to the M-ANNHEIM classification system) and those in whom kidney stones were diagnosed before CP diagnosis.ResultsSome 632 patients with definite CP were followed over a median of 5.3 (IQR 2.4–6.9) years. There were 41 (6.5%) patients diagnosed with kidney stones, of whom 33 (80.5%) were symptomatic. Comparing to patients without kidney stones, patients with nephrolithiasis were older, with median age of 65 (IQR 51–72) years, and a male predominance (80% vs 63%). Cumulative incidence of kidney stones was 2.1%, 5.7%, 12.4% and 16.1% at 5, 10, 15, and 20 years after CP diagnosis, respectively. Multivariable cause-specific Cox regression analysis revealed PEI as independent risk factor for nephrolithiasis (adjusted HR 4.95, 95%CI 1.65–14.84; p = 0.004). Another risk factors were increase in BMI (aHR 1.16 95% CI 1.04–1.30; p = 0.001 per unit increment), and a male sex (4.51, 95% CI 1.01–20.3, p = 0.049).ConclusionPEI and increase in BMI are risk factors for kidney stone development in patients with CP. Male CP patents are particularly at increased risk of nephrolithiasis. This should be taken into consideration in general clinical approach to raise awareness among patients and medical workers.     

Alcohol-Mediated Renal Denervation Using the Peregrine System Infusion Catheter for Treatment of Hypertension

ObjectivesThe aim of this multicenter, open-label trial was to evaluate the safety and efficacy of alcohol-mediated renal denervation using a novel catheter system (the Peregrine System Infusion Catheter) for the infusion of dehydrated alcohol as a neurolytic agent into the renal periarterial space.BackgroundThe number of hypertensive patients with uncontrolled blood pressure (BP) remains unacceptably high. The renal sympathetic nervous system has been identified as an attractive therapeutic target.MethodsForty-five patients with uncontrolled hypertension on ≥3 antihypertensive medications underwent bilateral renal denervation using the Peregrine Catheter with 0.6 ml alcohol infused per renal artery.ResultsAll patients were treated as intended. Mean 24-h ambulatory BP reduction at 6 months versus baseline was −11 mm Hg (95% confidence interval [CI]: −15 to −7 mm Hg) for systolic BP and −7 mm Hg (95% CI: −9 to −4 mm Hg) for diastolic BP (p < 0.001 for both). Office systolic BP was reduced by −18/−10 mm Hg (95% CI: −25 to −12/−13 to −6 mm Hg) at 6 months. Antihypertensive medications were reduced in 23% and increased in 5% of patients at 6 months. Adherence to the antihypertensive regimen remained stable over time. The primary safety endpoint, defined as the absence of periprocedural major vascular complications, major bleeding, acute kidney injury, or death within 1 month, was met in 96% of patients (95% CI: 85% to 99%). Two patients had major adverse events of periprocedural access-site pseudoaneurysms, with major bleeding in one. There were no deaths or instances of myocardial infarction, stroke, transient ischemic attack, or renal artery stenosis. Transient microleaks were noted in 42% and 49% of the left and right main renal arteries, respectively. There were 2 cases of minor vessel dissection that resolved without treatment.ConclusionsPrimary results from this trial suggest that alcohol-mediated renal denervation using the Peregrine Catheter safely reduces blood pressure and as such may represent a novel approach for the treatment of hypertension.     

Right Atrial/Pulmonary Arterial Wedge Pressure Ratio in Primary and Mixed Constrictive Pericarditis

BackgroundCardiac filling pressures may be elevated due to abnormalities in the myocardium, heightened pericardial restraint, or both. The authors hypothesized that the relative contributions due to myocardium and pericardium could be estimated by the ratio between right atrial pressure and pulmonary arterial wedge pressure (RAP/PAWP), which would enable better discrimination of the extent of myocardial disease in patients with constrictive pericarditis (CP).ObjectivesThis study investigated the relationships between RAP/PAWP and the pericardial thickness as well as echocardiographic parameters of myocardial function and assessed the prognostic implications of RAP/PAWP for long-term mortality in primary and mixed CP patients who underwent pericardiectomy.MethodsA total of 113 surgically confirmed CP patients who underwent echocardiography and cardiac catheterization within 7 days of each other between 2005 and 2013 were included in the study. The patients were classified into a high RAP/PAWP group (≥0.77; n = 56) or a low RAP/PAWP group (<0.77; n = 57) according to the median RAP/PAWP value. The primary outcome was prognostic implication of RAP/PAWP on long-term mortality and assessment of the relationship between RAP/PAWP and Doppler echocardiographic parameters in primary and mixed CP. In addition, the relationship between RAP/PAWP and the pericardial thickness was assessed.ResultsRAP/PAWP was directly correlated with pericardial thickness (regression coefficient [β] = 8.34; p < 0.001). RAP/PAWP had a significant direct correlation with early diastolic velocity of medial mitral annulus (eʹ) (β = 10.69; p < 0.001) and inverse relationship with early transmitral diastolic velocity (E) (β = −105.15; p < 0.001), resulting in an inverse relationship with the ratio of E/eʹ (β = −23.53; p < 0.001). Patients with high RAP/PAWP ratio had a better survival rate compared with those with low RAP/PAWP ratio (p = 0.01). Its prognostic value was significant in primary CP (p = 0.03) but not in mixed CP with concomitant myocardial disease (p = 0.89).ConclusionsThe RAP/PAWP ratio can reflect the degree of pericardial restraint versus restrictive myocardium and was associated with the long-term survival after pericardiectomy.     

Pulmonary Artery Denervation for Pulmonary Arterial Hypertension: A Sham-Controlled Randomized PADN-CFDA Trial

BackgroundWorld Health Organization (WHO) group 1 pulmonary arterial hypertension (PAH) is a progressive, debilitating disease. Previous observational studies have demonstrated that pulmonary artery denervation (PADN) reduces pulmonary artery pressures in PAH. However, the safety and effectiveness of PADN have not been established in a randomized trial.ObjectivesThe aim of this study was to determine the treatment effects of PADN in patients with group 1 PAH.MethodsPatients with WHO group 1 PAH not taking PAH-specific drugs for at least 30 days were enrolled in a multicenter, sham-controlled, single-blind, randomized trial. Patients were assigned to receive PADN plus a phosphodiesterase-5 inhibitor or a sham procedure plus a phosphodiesterase-5 inhibitor. The primary endpoint was the between-group difference in the change in 6-minute walk distance from baseline to 6 months.ResultsAmong 128 randomized patients, those treated with PADN compared with sham had a greater improvement in 6-minute walk distance from baseline to 6 months (mean adjusted between-group difference 33.8 m; 95% CI: 16.7-50.9 m; P < 0.001). From baseline to 6 months, pulmonary vascular resistance was reduced by ?3.0 ± 0.3 WU after PADN and ?1.9 ± 0.3 WU after sham (adjusted difference ?1.4; 95% CI: ?2.6 to ?0.2). PADN also improved right ventricular function, reduced tricuspid regurgitation, and decreased N-terminal pro–brain natriuretic peptide. Clinical worsening was less (1.6% vs 13.8%; OR: 0.11; 95% CI: 0.01-0.87), and a satisfactory clinical response was greater (57.1% vs 32.3%; OR: 2.79; 95% CI: 1.37-5.82) with PADN treatment during 6-month follow-up.ConclusionsIn patients with WHO group 1 PAH, PADN improved exercise capacity, hemodynamic status, and clinical outcomes during 6-month follow-up. (Safety and Efficacy of Pulmonary Artery Denervation in Patients With Pulmonary Arterial Hypertension [PADN-CFDA]; NCT03282266)     

Association between body mass index and mortality in atrial fibrillation patients with and without diabetes mellitus: Insights from a multicenter registry study in China

Background and aimsThe aim of this study was to evaluate the association between body mass index (BMI) and mortality in atrial fibrillation (AF) patients with and without diabetes mellitus (DM).Methods and resultsA total of 1991 AF patients were enrolled and divided into two groups according to whether they have DM at recruitment. Baseline information was collected and a mean follow-up of 1 year was carried out. The primary outcome was defined as all-cause mortality with the secondary outcomes including cardiovascular mortality, stroke and major adverse events (MAEs). Univariable and multivariable Cox regression were performed to estimate the association between BMI and 1-year outcomes in AF patients with and without DM. 309 patients with AF (15.5%) had comorbid DM at baseline. Patients with DM were more likely to have cardiovascular comorbidities, receive relevant medications but carry worse 1-year outcomes. Multivariable Cox regressions indicated that elevated BMI was related with reduced risk of all-cause mortality, cardiovascular mortality and major adverse events. Compared to normal weight, overweight [HR (95% CI): 0.548 (0.405–0.741), p < 0.001] and obesity [HR (95% CI): 0.541 (0.326–0.898), p = 0.018] were significantly related with decreased all-cause mortality for the entire cohort. Remarkably reduced all-cause mortality in the overweight [HR (95% CI): 0.497 (0.347–0.711), p < 0.001] and obesity groups [HR (95% CI): 0.405 (0.205–0.800), p = 0.009] could also be detected in AF patients without DM, but not in those with DM.ConclusionElevated BMI was associated with reduced mortality in patients with AF. This association was modified by DM. The obesity paradox confined to AF patients without DM, but could not be generalized to those with DM.     

5-Year Prognostic Value of Quantitative Versus Visual MPI in Subtle Perfusion Defects: Results From REFINE SPECT

ObjectivesThis study compared the ability of automated myocardial perfusion imaging analysis to predict major adverse cardiac events (MACE) to that of visual analysis.BackgroundQuantitative analysis has not been compared with clinical visual analysis in prognostic studies.MethodsA total of 19,495 patients from the multicenter REFINE SPECT (REgistry of Fast Myocardial Perfusion Imaging with NExt generation SPECT) study (64 ± 12 years of age, 56% males) undergoing stress Tc-99m-labeled single-photon emission computed tomography (SPECT) myocardial perfusion imaging were followed for 4.5 ± 1.7 years for MACE. Perfusion abnormalities were assessed visually and categorized as normal, probably normal, equivocal, or abnormal. Stress total perfusion deficit (TPD), quantified automatically, was categorized as TPD = 0%, TPD >0% to <1%, ≤1% to <3%, ≤3% to <5%, ≤5% to ≤10%, or TPD >10%. MACE consisted of death, nonfatal myocardial infarction, unstable angina, or late revascularization (>90 days). Kaplan-Meier and Cox proportional hazards analyses were performed to test the performance of visual and quantitative assessments in predicting MACE.ResultsDuring follow-up examinations, 2,760 (14.2%) MACE occurred. MACE rates increased with worsening of visual assessments, that is, the rate for normal MACE was 2.0%, 3.2% for probably normal, 4.2% for equivocal, and 7.4% for abnormal (all p < 0.001). MACE rates increased with increasing stress TPD from 1.3% for the TPD category of 0% to 7.8% for the TPD category of >10% (p < 0.0001). The adjusted hazard ratio (HR) for MACE increased even in equivocal assessment (HR: 1.56; 95% confidence interval [CI]: 1.37 to 1.78) and in the TPD category of ≤3% to <5% (HR: 1.74; 95% CI: 1.41 to 2.14; all p < 0.001). The rate of MACE in patients visually assessed as normal still increased from 1.3% (TPD = 0%) to 3.4% (TPD ≥5%) (p < 0.0001).ConclusionsQuantitative analysis allows precise granular risk stratification in comparison to visual reading, even for cases with normal clinical reading.     

The Prognostic Value of CAC Zero Among Individuals Presenting With Chest Pain: A Meta-Analysis

BackgroundThere is little consensus on whether absence of coronary artery calcium (CAC) can identify patients with chest pain (CP) who can safely avoid additional downstream testing.ObjectivesThe purpose of this study was to conduct a systematic review and meta-analysis investigating the utility of CAC assessment for ruling out obstructive coronary artery disease (CAD) among patients with stable and acute CP, at low-to-intermediate risk of obstructive CAD undergoing coronary computed tomography angiography (CTA).MethodsThe authors searched online databases for studies published between 2005 and 2021 examining the relationship between CAC and obstructive CAD (≥50% coronary luminal narrowing) on coronary CTA among patients with stable and acute CP.ResultsIn this review, the authors included 19 papers comprising 79,903 patients with stable CP and 13 papers including 12,376 patients with acute CP undergoing simultaneous CAC and coronary CTA assessment. Overall, 45% (95% CI: 40%-50%) of patients with stable CP and 58% (95% CI: 50%-66%) of patients with acute CP had CAC = 0. The negative predictive values for CAC = 0 ruling out obstructive CAD were 97% (95% CI: 96%-98%) and 98% (95% CI: 96%-99%) among patients with stable and acute CP, respectively. Additionally, the prevalence of nonobstructive CAD among those with CAC = 0 was 13% (95% CI: 10%-16%) among those with stable CP and 9% (95% CI: 5%-13%) among those with acute CP. A CAC score of zero predicted a low incidence of major adverse cardiac events among patients with stable CP (0.5% annual event rate) and acute CP (0.8% overall event rate).ConclusionsAmong over 92,000 patients with stable or acute CP, the absence of CAC was associated with a very low prevalence of obstructive CAD, a low prevalence of nonobstructive CAD, and a low annualized risk of major adverse cardiac events. These findings support the role of CAC = 0 in a value-based health care delivery model as a “gatekeeper” for more advanced imaging among patients presenting with CP.     

Evolution of Myocardial Dysfunction in Asymptomatic Patients at Risk of Heart Failure

ObjectivesThe determinants of changes in systolic and diastolic parameters in patients age >65 years, at risk of heart failure (HF), and with and without asymptomatic type 2 diabetes mellitus (T2DM) was assessed by echocardiography. The association between metformin and myocardial function was also assessed.BackgroundThe increasing prevalence of T2DM will likely further fuel the epidemic of HF. Understanding the development or progression of left ventricular (LV) dysfunction may inform effective measures for HF prevention.MethodsA total of 982 patients with at least one HF risk factor (hypertension, obesity, or T2DM) were recruited from 2 community-based populations and divided into 2 groups: T2DM (n = 431, age 71 ± 4 years) and non-T2DM (n = 551, age 71 ± 5 years). Associations of metformin therapy were evaluated in the T2DM group. All underwent a comprehensive echocardiogram, including global longitudinal strain (GLS) and diastolic function (transmitral flow [E], annular velocity [e’]) at baseline and follow-up (median 19 months [interquartile range: 17 to 26 months]). Comparisons were facilitated by propensity matching.ResultsA reduction in GLS was observed in the T2DM group (baseline ?17.8 ± 2.6% vs. follow-up ?17.4 ± 2.8%; p = 0.003), but not in the non-T2DM group (?18.7 ± 2.7% vs. ?18.6 ± 3.0%; p = 0.41). Estimated LV filling pressures increased in both the T2DM group (p = 0.001) and the non-T2DM group (p = 0.04). Metformin-treated patients with T2DM did not increase estimated LV filling pressure (E/e’ baseline 8.9 ± 2.7 vs. follow-up 9.1 ± 2.7; p = 0.485) or change e’ (7.6 ± 1.5 cm/s vs. 7.6 ± 1.8 cm/s; p = 0.88). After propensity matching, metformin was associated with a smaller change in e’ (β = 0.58 [95% CI: 0.13 to 1.03]; p = 0.013) and E/e’ (β = ?0.96 [95% CI: ?1.66 to ?0.26]; p = 0.007) but was not associated with a change in GLS (p = 0.46).ConclusionsOver 2 years, there is a worsening of GLS and LV filling pressures in asymptomatic diabetic patients with HF risk factors. Metformin use is associated with less deterioration of LV filling pressures and myocardial relaxation but had no association with systolic function.     

The Use and Outcomes of Cerebral Protection Devices for Patients Undergoing Transfemoral Transcatheter Aortic Valve Replacement in Clinical Practice

ObjectivesThis study hypothesized that cerebral protection prevents strokes in patients undergoing transfemoral transcatheter aortic valve replacement (TAVR) in clinical practice.BackgroundPreventing strokes is an important aim in TAVR procedures. Embolic protection devices may protect against cardiac embolism during TAVR, but their use and outcomes in clinical practice remain controversial.MethodsIsolated transfemoral TAVR procedures performed in Germany with or without cerebral protection devices were extracted from a comprehensive nationwide billing dataset.ResultsA total of 41,654 TAVR procedures performed between 2015 and 2017 were analyzed. The overall share of procedures incorporating cerebral protection devices was 3.8%. Patients receiving cerebral protection devices were at increased operative risk (European System for Cardiac Operative Risk Evaluation score 13.8 vs. 14.7; p < 0.001) but of lower age (81.1 vs. 80.6 years; p = 0.001). To compare outcomes that may be related to the use of cerebral protection devices, a propensity score comparison was performed. The use of a cerebral protection device did not reduce the risk for stroke (adjusted risk difference [aRD]: +0.88%; 95% confidence interval [CI]: ?0.07% to 1.83%; p = 0.069) or the risk for developing delirium (aRD: +1.31%; 95% CI: ?0.28% to 2.89%; p = 0.106) as a sign of acute brain failure. Although brain damage could not be prevented, in-hospital mortality was lower in the group receiving a cerebral protection device (aRD: ?0.76%; 95% CI: ?1.46% to ?0.06%; p = 0.034).ConclusionsIn this large national database, cerebral embolic protection devices were infrequently used during TAVR procedures. Device use was associated with lower mortality but not a reduction in stroke or delirium. Future studies are needed to confirm these findings.     

Rivaroxaban Plus Aspirin in Obese and Overweight Patients With Vascular Disease in the COMPASS Trial

BackgroundDirect oral anticoagulants are administered in fixed doses irrespective of body weight, but guidelines recommend against their use in patients with extremes of body weight.ObjectivesThis study determined the effects of dual-pathway inhibition antithrombotic regimen (rivaroxaban 2.5 mg twice daily plus aspirin 100 mg/day) compared with aspirin Halone across a range of patient body mass indexes (BMIs) and body weights.MethodsThis was a secondary analysis of the COMPASS (Cardiovascular OutcoMes for People using Anticoagulation StrategieS) trial, which included patients with chronic coronary artery disease or peripheral artery disease. Efficacy and safety outcomes were studied in relation to BMI: (normal 18.5 ≤BMI <25 kg/m², overweight 25 ≤BMI <30 kg/m², obese ≥30 kg/m²) and body weight (≤70 kg, 70 < weight ≤90 kg, and >90 kg; as well as ≤120 kg vs. >120 kg).ResultsAmong 27,395 randomized patients, 6,459 (24%) had normal BMI, 12,047 (44%) were overweight, and 8,701 (32%) were obese. The combination of rivaroxaban and aspirin compared with aspirin produced a consistent reduction in the primary outcome of cardiovascular death, stroke, or myocardial infarction, irrespective of BMI or body weight. For 18.5 ≤BMI <25 kg/m²: 3.5% vs. 5.0%; hazard ratio (HR): 0.73 (95% credible interval [CrI]: 0.58 to 0.90); 25 ≤ BMI <30 kg/m²: 4.3% vs. 5.1%; HR: 0.80 (95% CrI: 0.66 to 0.96); BMI ≥30 kg/m²: 4.2% vs. 6.1%; HR: 0.71 (95% CrI: 0.57 to 0.86). For body weight ≤70 kg: 4.1% vs. 5.3%; HR: 0.75 (95% CrI: 0.62 to 0.91); 70 < weight ≤90 kg: 4.1% vs. 5.3%; HR: 0.76 (95% CrI: 0.65 to 0.89); >90 kg: 4.2% vs. 5.7%; HR: 0.74 (95% CrI: 0.61 to 0.90). Effects on bleeding, mortality, and net clinical benefit were consistent irrespective of BMI or bodyweight.ConclusionsThe effects of dual-pathway antithrombotic therapy are consistent irrespective of BMI or body weight, suggesting no need for dose adjustments in the ranges of weights and BMI of patients enrolled in the COMPASS trial. Further studies need to address this problem in relation to greater extremes of body weight. (Rivaroxaban for the Prevention of Major Cardiovascular Events in Coronary or Peripheral Artery Disease [COMPASS]; NCT01776424)     

Causal associations of body mass index and waist-to-hip ratio with cardiometabolic traits among Chinese children: A Mendelian randomization study

Background and aimsBody mass index (BMI) and waist-to-hip ratio (WHR) have been reported to be causally associated with cardiometabolic diseases in adults in European populations. However, this causality was less explored in East Asian populations and in children. Our study aimed to explore and compare the causal associations of general obesity (measured by BMI) and central obesity (measured by WHR) with cardiometabolic traits.Methods and resultsWe performed a Mendelian randomization (MR) analysis in 2030 unrelated children from two independent case–control studies in Beijing, China. BMI-associated single nucleotide polymorphisms (SNPs) and WHR-SNPs identified by previous genome-wide association studies were used as genetic instruments to examine the casual associations of BMI and WHR with cardiometabolic traits, including glycemic traits, blood lipids, and blood pressure. Each 1-SD increase in BMI and WHR were significantly associated with 0.111 mmol/L and 0.110 mmol/L increase in log-transformed fasting insulin (FINS), 0.049 and 0.060 increase in log-transformed HOMA-β, 0.112 and 0.108 increase in log-transformed HOMA-IR, 0.009 mmol/L and 0.015 mmol/L increase in log-transformed triglyceride, and 15.527 mmHg and 7.277 mmHg increase in systolic blood pressure, respectively (all P < 0.05). The receiver operating characteristic curves showed that WHR had a stronger effect on FINS, HOMA-β, HOMA-IR, and triglyceride than BMI (all P < 0.05).ConclusionsUsing the MR method, we found that the genetic predisposition to higher BMI or WHR was associated with altered cardiometabolic traits in Chinese children. When compared with general obesity, central obesity might have stronger effects on glycemic traits and blood lipids among children.     

Sex-specific association of BMI change with stroke in middle-aged and older adults with type 2 diabetes

Background and aimsWe aimed to evaluate the association between BMI change and stroke in middle-aged and older adults with type 2 diabetes and identify sex differences.Methods and resultsThe China Health and Retirement Longitudinal Study is an ongoing national population-based cohort study. Participants aged 45 or above with type 2 diabetes were enrolled and followed for stroke incidence. BMI change was defined as BMI at 2013-BMI at 2011. Of 1774 participants (mean [SD] age in 2011, 60.23 [8.88] years), 795 (44.8 %) were men. A total of 112 incident stroke cases were confirmed up to 2018. The incidence rate of stroke was similar between men and women (6.79 % vs 5.92 %, P = 0.516). BMI increase was independently associated with an increased stroke risk (adjusted odds ratio, 1.15; 95 % CI, 1.05–1.31) in men, while this positive association was not significant in women (adjusted odds ratio, 1.12; 95 % CI, 0.98–1.29). In addition, the positive dose–response relationship between BMI increase and stroke was observed only in men.ConclusionAmong middle-aged and older adults with type 2 diabetes, there is a sex-specific association of BMI change with stroke. An increase in BMI could result in a higher risk of incident stroke in men.