Combination of F-ASO and Targeted Medical Therapy in Patients With Secundum ASD and Severe PAH

ObjectivesThis study was conducted to investigate the combined use of fenestrated atrial septal occluder (F-ASO) and targeted medical therapy (TMT) in patients with secundum atrial septal defect (ASD) and severe pulmonary arterial hypertension (PAH).BackgroundTreatment of patients with ASD and severe PAH is still challenging.MethodsAfter ethical approval was obtained, 56 consecutive patients with ASD with severe PAH were included (7 men, 49 women; median age 50.5 years; mean ASD size 26.9 ± 4.6 mm). After 3 months of TMT, transcatheter closure was performed using F-ASO in patients with ratios of pulmonary to systemic blood flow ≥1.5. TMT was continued post-operatively together with 6 months of dual-antiplatelet therapy. The hemodynamic variables during baseline, TMT alone, and combined treatment with F-ASO were compared.ResultsAfter only TMT, systolic pulmonary arterial pressure (−14.5 mm Hg; p < 0.001), pulmonary vascular resistance (−3.9 Wood units; p < 0.001), and exercise capacity (+72.0 m; p < 0.001) improved. Ratio of pulmonary to systemic blood flow increased by 0.9 (p < 0.001), with adverse cardiac remodeling (right ventricular dimension +3.5 mm; p < 0.001). Closure with F-ASO (median size 34.0 mm) led to further decrease in systolic pulmonary artery pressure (−6.0 mm Hg; p < 0.001). Follow-up (median duration 10 months) revealed further improvement in exercise capacity (+60.5 m; p < 0.001), with favorable cardiac remodeling (right ventricular dimension −9.9 mm; p < 0.001). In addition, all fenestrations were stable (p = 0.699), with negligible shunt (median ratio of pulmonary to systemic blood flow 1.1) and no complications. One year later, pulmonary artery pressure was normalized in 8 of 19 patients, and PAH recurred in 5 patients after discontinuation of TMT.ConclusionsIn patients with ASD and severe PAH, combination of F-ASO and TMT was a safe and effective procedure. Compared with TMT alone, the combined treatment further improved exercise capacity, with favorable cardiac remodeling.     

Elevated interleukin levels are associated with higher severity and mortality in COVID 19 – A systematic review,meta-analysis,and meta-regression

Background and aimsCOVID 19 pneumonia commonly leads to ARDS. The occurrence of ARDS in COVID 19 patients is thought to occur secondary to an exaggerated immunologic response. In this meta-analysis, we aim to comprehensively study the various levels of immunological parameters in patients with COVID 19.Materials and methodsWe performed a systematic literature search from PubMed, EuropePMC, SCOPUS, Cochrane Central Database, and medRxiv with the search terms, “COVID-19” and “Interleukin”. The outcome of interest was prognosis in COVID 19 patients.ResultsWe performed meta analysis of 16 studies. Higher counts of CD4 and CD8 with Lower Levels of TNF-a, IL2R, IL6, IL8 were observed on patients with good prognosis compared to patients with poor prognosis; −0.57 (pg/mL) (−1.10, −0.04, p = 0.04), (I² 91%, p < 0.001); −579.84 (U/mL) (−930.11, −229.57, p < 0.001), (I² 96%, p < 0.001); −1.49 (pg/mL) (−1.97, −1.01, p < 0.001), (I² 94%, p < 0.001); −0.80 (pg/mL) (−1.21, −0.40, p < 0.001), (I2 79%, p < 0.001); −2.51 (pg/mL) (−3.64, −1.38, p < 0.00001), (I² 98%, p < 0.001) respectively. Meta-regression showed age and hypertension (coefficient: 1.99, and −1.57, p = 0.005, and 0.006) significantly influenced association between IL-6 and poor outcome.ConclusionElevated immune response to coronavirus occurs in COVID 19 patients. Higher counts of CD4 and CD8 were seen in patients with good prognosis compared to patients with poor prognosis, with Lower levels of TNF-a, IL2R, IL6, IL8, were observed in patients with good prognosis compared to patients with poor prognosis.     

Changes in Plasma Renin Activity After Renal Artery Sympathetic Denervation

BackgroundThe renin-angiotensin-aldosterone system plays a key role in blood pressure (BP) regulation and is the target of several antihypertensive medications. Renal denervation (RDN) is thought to interrupt the sympathetic-mediated neurohormonal pathway as part of its mechanism of action to reduce BP.ObjectivesThe purpose of this study was to evaluate plasma renin activity (PRA) and aldosterone before and after RDN and to assess whether these baseline neuroendocrine markers predict response to RDN.MethodsAnalyses were conducted in patients with confirmed absence of antihypertensive medication. Aldosterone and PRA levels were compared at baseline and 3 months post-procedure for RDN and sham control groups. Patients in the SPYRAL HTN-OFF MED Pivotal trial were separated into 2 groups, those with baseline PRA ≥0.65 ng/ml/h (n = 110) versus <0.65 ng/ml/h (n = 116). Follow-up treatment differences between RDN and sham control groups were adjusted for baseline values using multivariable linear regression models.ResultsBaseline PRA was similar between RDN and control groups (1.0 ± 1.1 ng/ml/h vs. 1.1 ± 1.1 ng/ml/h; p = 0.37). Change in PRA at 3 months from baseline was significantly greater for RDN compared with control subjects (?0.2 ± 1.0 ng/ml/h; p = 0.019 vs. 0.1 ± 0.9 ng/ml/h; p = 0.14), p = 0.001 for RDN versus control subjects, and similar differences were seen for aldosterone: RDN compared with control subjects (?1.2 ± 6.4 ng/dl; p = 0.04 vs. 0.4 ± 5.4 ng/dl; p = 0.40), p = 0.011. Treatment differences at 3 months in 24-h and office systolic blood pressure (SBP) for RDN versus control patients were significantly greater for patients with baseline PRA ≥0.65 ng/ml/h versus <0.65 ng/ml/h, despite similar baseline BP. Differences in office SBP changes according to baseline PRA were also observed earlier at 2 weeks post-RDN.ConclusionsPlasma renin activity and aldosterone levels for RDN patients were significantly reduced at 3 months when compared with baseline as well as when compared with sham control. Higher baseline PRA levels were associated with a significantly greater reduction in office and 24-h SBP. (SPYRAL PIVOTAL - SPYRAL HTN-OFF MED Study; NCT02439749)     

Diagnosis and management of postpancreatectomy hemorrhage: A single-center experience of consecutive 1,096 pancreatoduodenectomies

Background/objectivesThis study aimed to assess the outcomes and characteristics of post-pancreatectomy hemorrhage (PPH) in over 1000 patients who underwent pancreatoduodenectomy (PD) at a high-volume hepatopancreaticobiliary center.MethodsThis retrospective study analyzed consecutive patients who underwent PD from 2010 through 2021. PPH was diagnosed and managed using our algorithm based on timing of onset and location of hemorrhage.ResultsOf 1096 patients who underwent PD, 33 patients (3.0%) had PPH; incidence of in-hospital and 90-day mortality relevant to PPH were one patient (3.0%) and zero patients, respectively. Early (≤24 h after surgery) and late (>24 h) PPH affected 9 patients and 24 patients, respectively; 16 patients experienced late-extraluminal PPH. The incidence of postoperative pancreatic fistula (p < 0.001), abdominal infection (p < 0.001), highest values of drain fluid amylase (DFA) within 3 days, and highest value of C-reactive protein (CRP) within 3 days after surgery (DFA: p < 0.001) (CRP: p = 0.010) were significantly higher in the late-extraluminal-PPH group. The highest values of DFA≥10000U/l (p = 0.022), CRP≥15 mg/dl (p < 0.001), and incidence of abdominal infection (p = 0.004) were identified as independent risk factors for PPH in the multivariate analysis. Although the hospital stay was significantly longer in the late-extraluminal-PPH group (p < 0.001), discharge to patient's home (p = 0.751) and readmission rate within 30-day (p = 0.765) and 90-day (p = 0.062) did not differ between groups.ConclusionsStandardized management of PPH according to the onset and source of hemorrhage minimizes the incidence of serious deterioration and mortality. High-risk patients with PPH can be predicted based on the DFA values, CRP levels, and incidence of abdominal infections.     

Effects of weight loss medications on mortality and cardiovascular events: A systematic review of randomized controlled trials in adults with overweight and obesity

AimsAdults affected by obesity are at higher risk of premature mortality. Medications can help to lose weight and to maintain weight loss. Aim of this meta-analysis was to assess whether anti-obesity medications affect all-cause mortality, mortality due to cardiovascular events, cardiovascular risk factors and body weight.Data synthesisA Medline search was performed to identify randomized controlled trials (RCTs) of anti-obesity medications in adults with overweight or obesity reporting data on all-cause mortality, cardiovascular mortality or non-fatal cardiovascular events, with a follow-up of at least 6 months. We identified 28 RCTs with 50,106 participants. The median follow-up was 52 weeks. Evidence did not show superiority of anti-obesity medications over placebo in reducing all-cause mortality (risk ratio 1.03, 95%Confidence Interval [CI] 0.87 to 1.21) or cardiovascular mortality (risk ratio 0.92, 95%CI 0.72 to 1.18). All-cause mortality rate was positively associated with weight loss (β = 0.0007; p = 0.045); hence, for each kg of body weight lost there was a 0.07% decrease of all-cause mortality. The pharmacological treatment reduced total-cholesterol (7.15 mg/dl; 95%CI 1.46–12.85), LDL-cholesterol (5.06 mg/dl; 95%CI 1.12–9.00), and triglycerides levels (9.88 mg/dl; 95%CI 5.02–14.75), while it increased HDL-cholesterol (1.37 mg/dl; 95%CI 0.17–2.57). Systolic blood pressure decreased (0.90 mmHg; 95%CI 0.15–1.64).ConclusionsAlthough we were unable to demonstrate a superiority of anti-obesity medications over placebo on mortality, metaregression showed that even a small weight reduction tends to reduce all-cause mortality in obesity. Our data support public health measures to reduce the obesity burden by including the use of anti-obesity medications.Registration number (PROSPERO)CRD42020210329.     

Low LDL Cholesterol by PCSK9 Variation Reduces Cardiovascular Mortality

BackgroundReduced low-density lipoprotein (LDL) cholesterol due to inhibition of proprotein convertase subtilisin/kexin 9 (PCSK9) reduces cardiovascular events and may therefore also reduce cardiovascular and all-cause mortality.ObjectivesThis study tested the hypothesis that genetically low LDL cholesterol due to PCSK9 variation is causally associated with low cardiovascular and all-cause mortality in the general population.MethodsA total of 109,566 individuals from the Copenhagen General Population Study and the Copenhagen City Heart Study were genotyped for PCSK9 R46L (rs11591147), R237W (rs148195424), I474V (rs562556), and E670G (rs505151). During a median follow-up of 10 years (range 0 to 42 years) and 1,247,225 person-years, there were 3,828 cardiovascular deaths and 16,373 deaths from any cause. Results were validated using data on 431,043 individuals from the UK Biobank.ResultsAn increasing number of weighted PCSK9 alleles were associated with stepwise lower LDL cholesterol of up to 0.61 mmol/l (24 mg/dl; 18.2%; p for trend <0.001) and with lower cardiovascular mortality (p = 0.001), but not with lower all-cause mortality (p = 0.11). In causal, genetic analyses, a 0.5-mmol/l (19.4-mg/dl) lower LDL cholesterol was associated with risk ratios for cardiovascular and all-cause mortality of 0.79 (95% confidence interval [CI]: 0.63 to 0.99; p = 0.04) and 1.02 (95% CI: 0.94 to 1.12; p = 0.63) in the Copenhagen studies, 0.79 (95% CI: 0.58 to 1.08; p = 0.14) and 0.98 (95% CI: 0.87 to 1.10; p = 0.75) in the UK Biobank, and of 0.79 (95% CI: 0.65 to 0.95; p = 0.01) and 1.01 (95% CI: 0.94 to 1.08; p = 0.85), respectively, in studies combined.ConclusionsGenetically low LDL cholesterol due to PCSK9 variation was causally associated with low risk of cardiovascular mortality, but not with low all-cause mortality in the general population.     

Proposed Stages of Myocardial Phenotype Development in Fabry Disease

ObjectivesThis study sought to explore the Fabry myocardium in relation to storage, age, sex, structure, function, electrocardiogram changes, blood biomarkers, and inflammation/fibrosis.BackgroundFabry disease (FD) is a rare, x-linked lysosomal storage disorder. Mortality is mainly cardiovascular with men exhibiting cardiac symptoms earlier than women. By cardiovascular magnetic resonance, native T1 is low in FD because of sphingolipid accumulation.MethodsA prospective, observational study of 182 FD (167 adults, 15 children; mean age 42 ± 17 years, 37% male) who underwent cardiovascular magnetic resonance including native T1, late gadolinium enhancement (LGE), and extracellular volume fraction, 12-lead electrocardiogram, and blood biomarkers (troponin and N-terminal pro-brain natriuretic peptide).ResultsIn children, T1 was never below the normal range, but was lower with age (9 ms/year, r = −0.78 children; r = −0.41 whole cohort; both p < 0.001). Over the whole cohort, the T1 reduction with age was greater and more marked in men (men: −1.9 ms/year, r = −0.51, p < 0.001; women: −1.4 ms/year, r = −0.47 women, p < 0.001). Left ventricular hypertrophy (LVH), LGE, and electrocardiogram abnormalities occur earlier in men. Once LVH occurs, T1 demonstrates major sex dimorphism: with increasing LVH in women, T1 and LVH become uncorrelated (r = −0.239, p = 0.196) but in men, the correlation reverses and T1 increases (toward normal) with LVH (r = 0.631, p < 0.001), a U-shaped relationship of T1 to indexed left ventricular mass in men.ConclusionsThese data suggest that myocyte storage starts in childhood and accumulates faster in men before triggering 2 processes: a sex-independent scar/inflammation regional response (LGE) and, in men, apparent myocyte hypertrophy diluting the T1 lowering of sphingolipid.     

Long-Term Prognostic Impact of Restenosis of the Unprotected Left Main Coronary Artery Requiring Repeat Revascularization

ObjectivesThe aim of this study was to evaluate the prognostic impact of target lesion revascularization (TLR) of the unprotected left main coronary artery (ULMCA) after stent failure.BackgroundAlthough drug-eluting stents are safe and effective for treatment of the ULMCA, increased rates of repeat revascularization have been observed.MethodsThis is a patient-level pooled analysis of the randomized ISAR-LEFT-MAIN (Drug-Eluting-Stents for Unprotected Left Main Stem Disease) and ISAR-LEFT-MAIN-2 (Drug-Eluting Stents to Treat Unprotected Coronary Left Main Disease) trials, in which patients underwent stenting of the ULMCA. The present analysis includes patients who underwent angiography during follow-up. Patients with TLR were compared with those without. Additional long-term clinical follow-up after TLR was conducted, and its influence on mortality was evaluated. Mortality was calculated using the Kaplan-Meier method. Predictors of mortality were assessed in a multivariate analysis.ResultsA total of 1,001 patients were eligible, of whom 166 experienced TLR. The 5-year mortality rate was 30.2% in patients with TLR compared with 17.3% in those without TLR (p < 0.001). In the multivariate analysis, glomerular filtration rate (−30 ml/min; hazard ratio [HR]: 2.25; 95% confidence interval [CI]: 1.54 to 3.27; p < 0.001), chronic obstructive pulmonary disease (HR: 4.95; 95% CI: 1.33 to 18.42; p = 0.02), and body mass index (+5 kg/m²; HR: 1.61; 95% CI: 1.12 to 2.32; p = 0.01) were independent predictors of mortality after TLR due to left main stent failure. The type of repeat revascularization and the underlying stent did not influence the mortality after TLR of the ULMCA.ConclusionsMortality after TLR for left main stent failure is high. Patient-related factors seem to have a greater impact on mortality after TLR than other variables.     

Adverse Plaque Characteristics Relate More Strongly With Hyperemic Fractional Flow Reserve and Instantaneous Wave-Free Ratio Than With Resting Instantaneous Wave-Free Ratio

ObjectivesThe current substudy of the PACIFIC (Prospective Comparison of Cardiac PET/CT, SPECT/CT Perfusion Imaging and CT Coronary Angiography With Invasive Coronary Angiography) trial explores the impact of computed tomography (CT)–derived unfavorable plaque features on both hyperemic and non-hyperemic flow indices.BackgroundNext to lesion severity, plaque vulnerability as assessed using coronary CT angiography affects fractional flow reserve (FFR), which is associated with imminent acute coronary syndromes. Instantaneous wave-free ratio (iFR) has recently emerged as an alternative for FFR to interrogate coronary lesions for ischemia. It is, however, unknown whether vasodilator-free assessment with iFR is associated with plaque stability similarly as FFR.MethodsOf 120 patients (62% men, age 58.3 ± 8.6 years) with suspected coronary artery disease, 257 vessels were prospectively evaluated. Each patient underwent 256-slice coronary CT angiography to assess stenosis severity and plaque features (positive remodeling [PR], low attenuation plaque [LAP], spotty calcification [SC], and napkin ring sign [NRS]), as well as intracoronary pressure measurements (FFR, iFR, Pd/Pa, and pressure ratio during adenosine within the wave-free period [iFRa]). CT-derived plaque characteristics were related to these invasive pressure measurements.ResultsAtherosclerotic plaques were present in 170 (66%) coronary arteries. On a per-vessel basis, luminal stenosis severity was significantly associated with impaired FFR, iFR, Pd/Pa, and iFRa. Multivariable analysis revealed that FFR and iFR were independently related to ≥70% stenosis (−0.10, p < 0.001 and −0.09, p = 0.003, respectively) and plaque volume (-0.02, p = 0.020 and -0.02, p = 0.030, respectively). Additionally, PR and SC were also independent predictors of an impaired FFR (−0.10, p < 0.001 and −0.07, p = 0.021, respectively), but adverse plaque characteristics were not independently related to the vasodilator-free iFR.ConclusionsCT-derived vulnerable plaque characteristics are independently associated with hyperemic flow indices as assessed with FFR and iFRa, but not with non-hyperemic indices such as iFR and Pd/Pa. These findings suggest that the effects of hyperemia on pressure-derived indices might depend not only on hemodynamic stenosis severity but also on plaque characteristics.     

Sex Differences in Compositional Plaque Volume Progression in Patients With Coronary Artery Disease

ObjectivesThis study sought to explore sex-based differences in total and compositional plaque volume (PV) progression.BackgroundIt is unclear whether sex has an impact on PV progression in patients with coronary artery disease (CAD).MethodsThe study analyzed a prospective multinational registry of consecutive patients with suspected CAD who underwent 2 or more clinically indicated coronary computed tomography angiography (CTA) at ≥2-year intervals. Total and compositional PV at baseline and follow-up were quantitatively analyzed and normalized using the analyzed total vessel length. Multivariate linear regression models were constructed.ResultsOf the 1,255 patients included (median coronary CTA interval 3.8 years), 543 were women and 712 were men. Women were older (62 ± 9 years of age vs. 59 ± 9 years of age; p < 0.001) and had higher total cholesterol levels (195 ± 41 mg/dl vs. 187 ± 39 mg/dl; p = 0.002). Prevalence of hypertension, diabetes, and family history of CAD were not different (all p > 0.05). At baseline, men possessed greater total PV (31.3 mm³ [interquartile range (IQR): 0 to 121.8 mm³] vs. 56.7 mm³ [IQR: 6.8 to 152.1 mm³] p = 0.005), and there was an approximately 9-year delay in women in developing total PV than in men. The prevalence of high-risk plaques was greater in men than women (31% vs. 20%; p < 0.001). In multivariate analysis, after adjusting for age, clinical risk factors, medication use, and total PV at baseline, despite similar total PV progression rates, female sex was associated with greater calcified PV progression (β = 2.83; p = 0.004) but slower noncalcified PV progression (β = –3.39; p = 0.008) and less development of high-risk plaques (β = –0.18; p = 0.049) than in men.ConclusionsThe compositional PV progression differed according to sex, suggesting that comprehensive plaque evaluation may contribute to further refining of risk stratification according to sex. (NCT02803411).     

Impact of etiology on disease course in chronic pancreatitis

BackgroundComplications in chronic pancreatitis (CP) can be grouped in inflammatory (ICC) and fibrotic (FCC) clusters and pancreatic insufficiency cluster (PIC). However, the association between etiological risk factors and the development of complication clusters remains obscure. In this study, the impact of the etiology and disease duration on disease onset and development of complications was investigated.MethodsThis cross-sectional study recruited patients with CP from Mannheim/Germany (n = 870), Gieβen/Germany (n = 100) und Donetsk/Ukraine (n = 104). Etiological risk factors, disease stage, age at disease onset, complications, need for hospitalization and surgery were noted.ResultsIn 1074 patients diagnosed with CP, main risk factors were alcohol and nicotine abuse. An earlier onset of the disease was observed upon nicotine abuse (−4.0 years). Alcohol abuse was only associated with an earlier onset of the definite stage of CP.Alcohol abuse was the major risk factor for the development of ICC (p < 0.0001, multiple regression modeling). Abstinence of alcohol reduced ICC, whereas abstinence of nicotine showed no association. PIC correlated with efferent duct abnormalities and the disease duration. In contrast, FCC was mainly dependent on the disease duration (p < 0.0001; t-test). The presence of any complication cluster correlated with the need for surgery (p < 0.01; X²-test). However, only ICC correlated with a prolonged hospital stay (p < 0.05; t-test).ConclusionsICC is mainly dependent on alcohol abuse. In contrast, FCC and PIC are mainly dependent on the disease duration. The etiology and disease duration can be used as predictors of the course of disease to provide individual treatment and surveillance strategies.     

Urinary Dickkopf-3 and Contrast-Associated Kidney Damage

BackgroundAdministration of iodinated contrast medium (CM) during invasive cardiovascular procedures may be associated with impairment of kidney function.ObjectivesUrinary dickkopf-3 (DKK3), a stress-induced renal tubular epithelium–derived glycoprotein, has been identified as a biomarker predicting both acute kidney injury (AKI) and persistent kidney dysfunction.MethodsUrinary DKK3/creatinine ratio (uDKK3/uCr), urine and serum neutrophil gelatinase-associated lipocalin (uNGAL, sNGAL) and serum cystatin C (sCyC) were assessed in 458 patients with chronic kidney disease scheduled for invasive cardiovascular procedures requiring CM administration with universal adoption of nephroprotective interventions. Contrast-associated AKI (CA-AKI) was defined as serum creatinine increase ≥0.3 mg/dl at 48 h after CM administration. Persistent kidney dysfunction was defined as persistent estimated glomerular filtration rate reduction ≥25% at 1 month compared with baseline.ResultsCA-AKI occurred in 64 or the 458 patients (14%), and baseline uDKK3/uCr ≥491 pg/mg was the best threshold for its prediction. Net reclassification improvement (NRI) was significantly increased by adding baseline uDKK3/uCr to the Mehran, Gurm, and National Cardiovascular Data Registry (NCDR) scores (all p < 0.05), and the same applied to integrated discrimination improvement (IDI) when adding uDKK3/uCr to the Gurm and NCDR scores (p < 0.001). Persistent kidney dysfunction occurred in 57 of the 458 patients (12%) and baseline uDKK3/uCr ≥322 pg/mg appeared as the best threshold for its prediction. Adding baseline uDKK3/uCr to the Mehran, Gurm, and NCDR scores significantly increased IDI and NRI (all p < 0.001).ConclusionsBaseline uDKK3/uCr seems to be a reliable marker for improving the identification of patients with chronic kidney disease undergoing invasive coronary and peripheral procedures at risk for AKI and persistent kidney dysfunction.     

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.     

Clinical characteristics,outcomes, and factors associated with mortality in Nocardia pneumonia: 18 years' real-world data from a tertiary care hospital in Karachi,Pakistan

BackgroundPulmonary nocardiosis is a rare pulmonary infection with high morbidity and mortality. Limited real-world data on pulmonary nocardiosis patients are available from developing countries like Pakistan.MethodsThis retrospective observational study was conducted at the Aga Khan University Hospital, Karachi, Pakistan, from August 2003 to June 2020. Demographics, immune status, underlying diseases, laboratory data, treatment, and outcomes of all nocardiosis patients were recorded in predesigned proforma.ResultsSixty-six patients with smear/culture-proven pulmonary nocardiosis were identified. Most patients (83.3%) were treated with trimethoprim-sulfamethoxazole alone or in combination with other medicines. The overall mortality rate in our study was 33.3% (n = 22/66). Factors significantly associated with mortality were respiratory failure (p < 0.001), raised procalcitonin levels (p = 0.01), concomitant fungal infections (p = 0.01), concomitant TB (p = 0.03), and patients on combination therapy (p < 0.001).Respiratory failure (odds ratio [OR] 46.94 [95% confidence intervals [CI]: 5.01–439.03] p < 0.001), concomitant fungal infection (OR 17.09 [95% CI: 1.47–197.88] p- = 0.02) and patients on combination therapy (OR 6.90 [95% CI: 1.23–38.61] p = 0.02) were also identified as independent risk factors for mortality on multivariate analysis.ConclusionsThis study provides essential information on the clinical characteristics and risk factors, outcomes, and factors associated with mortality for pulmonary nocardial infections.     

Microvascular Dysfunction in Dilated Cardiomyopathy: A Quantitative Stress Perfusion Cardiovascular Magnetic Resonance Study

ObjectivesThis study sought to quantify myocardial blood flow (MBF) and myocardial perfusion reserve (MPR) in dilated cardiomyopathy (DCM) and examine the relationship between myocardial perfusion and adverse left ventricular (LV) remodeling.BackgroundAlthough regarded as a nonischemic condition, DCM has been associated with microvascular dysfunction, which is postulated to play a role in its pathogenesis. However, the relationship of the resulting perfusion abnormalities to myocardial fibrosis and the degree of LV remodeling is unclear.MethodsA total of 65 patients and 35 healthy control subjects underwent adenosine (140 μg/kg/min) stress perfusion cardiovascular magnetic resonance with late gadolinium enhancement imaging. Stress and rest MBF and MPR were derived using a modified Fermi-constrained deconvolution algorithm.ResultsPatients had significantly higher global rest MBF compared with control subjects (1.73 ± 0.42 ml/g/min vs. 1.14 ± 0.42 ml/g/min; p < 0.001). In contrast, global stress MBF was significantly lower versus control subjects (3.07 ± 1.02 ml/g/min vs. 3.53 ± 0.79 ml/g/min; p = 0.02), resulting in impaired MPR in the DCM group (1.83 ± 0.58 vs. 3.50 ± 1.45; p < 0.001). Global stress MBF (2.70 ± 0.89 ml/g/min vs. 3.44 ± 1.03 ml/g/min; p = 0.017) and global MPR (1.67 ± 0.61 vs. 1.99 ± 0.50; p = 0.047) were significantly reduced in patients with DCM with LV ejection fraction ≤35% compared with those with LV ejection fraction >35%. Segments with fibrosis had lower rest MBF (mean difference: −0.12 ml/g/min; 95% confidence interval: −0.23 to −0.01 ml/g/min; p = 0.035) and lower stress MBF (mean difference: −0.15 ml/g/min; 95% confidence interval: −0.28 to −0.03 ml/g/min; p = 0.013).ConclusionsPatients with DCM exhibit microvascular dysfunction, the severity of which is associated with the degree of LV impairment. However, rest MBF is elevated rather than reduced in DCM. If microvascular dysfunction contributes to the pathogenesis of DCM, then the underlying mechanism is more likely to involve stress-induced repetitive stunning rather than chronic myocardial hypoperfusion.     

Short-term outcomes following coronary artery bypass graft surgery in insulin treated and non-insulin treated diabetes: A tertiary hospital experience in Australia

Background and aimsOutcomes after coronary artery bypass graft (CABG) surgery have improved due to advances in surgical technique and post-operative care. We aimed to describe contemporary clinical characteristics and short-term post-operative outcomes in diabetic patients undergoing CABG surgery.MethodsA retrospective analysis of patients who underwent CABG surgery over a 4.5-year period in a Western Australian tertiary hospital was performed in September 2019. The cohort was stratified according to pre-operative diabetes status.ResultsA total of 1327 patients underwent CABG surgery, of which 572 (43.1%) had diabetes. Diabetic patients were more likely to be female (24.7% vs. 13.9%, p < 0.001) and have dyslipidaemia (83.0% vs. 68.1%, p < 0.001), hypertension (82.0% vs. 68.7%, p < 0.001), raised body mass index (29.8 ± 5.6 vs. 28.7 ± 5.1 kg/m², p < 0.001), prior myocardial infarction (62.8% vs. 54.8%, p = 0.004), prior stroke (8.6% vs. 5.0%, p = 0.010), congestive cardiac failure (20.2% vs. 15.1%, p = 0.014), reduced estimated glomerular filtration rate (86.7 ± 36.1 vs. 90.8 ± 32.1 ml/min/1.73 m², p = 0.036) and three-vessel coronary artery disease (74.8% vs. 67.3%, p = 0.003). Post-operative wound infections (3.1% vs. 1.5%, p = 0.022), new dialysis requirement (2.9% vs. 1.0%, p = 0.009) and 30-day hospital admission (13.1% vs. 8.5%, p = 0.007) was more likely in diabetic patients, but not myocardial infarction (3.0% vs. 2.0%, p = 0.247), stroke (1.4% vs. 0.8%, p = 0.286) or 30-day mortality (2.4% vs. 1.7%, p = 0.354). No significant differences were detected in short-term outcomes between patients with non-insulin (n = 398) versus insulin treated (n = 174) diabetes.ConclusionsDiabetic patients continue to represent a higher-risk cohort, highlighting the need for further strategies to reduce short-term adverse outcomes following CABG surgery.     

Implementing DASH-aligned Congregate Meals and Self-Measured Blood Pressure in two senior centers: An open label study

Background and aimsCardiovascular Disease (CVD) poses significant health risks for seniors, especially among low-income and minority communities. Senior centers offer multiple services. We tested whether implementing two evidence-based interventions- DASH-aligned meals provided through an existing congregate meal program, and support for home Self-Measured Blood Pressure (SMBP) monitoring-lowers blood pressure among participants at two senior centers serving low-income, racially diverse communities.Methods and resultsOpen-label study, enrolling clients aged ≥60, eating ≥4 meals/week at two NYC senior centers. Participants received DASH-aligned congregate meals, and training in nutrition, BP management education, and personal SMBP device. Co-Primary outcomes: a) change in systolic BP measured by independent health professionals, and b) change in percent with “controlled BP” (Eighth Joint National Committee (JNC-8) Guidelines), at Month 1 compared to Baseline. Secondary outcomes: Changes in BP at Months 3 and 5/6 (last measure).We enrolled 94 participants; COVID closures interrupted implementation mid-study. Mean systolic BP at Month-1 changed by ?4.41 mmHg (n = 61 p = 0.07) compared to Baseline. Participants with controlled BP increased (15.7%) at Month 1. Change in mean BP at Month 1 was significantly correlated with BMI (p = 0.02), age (p = 0.04), and baseline BP (p < 0.001). Mean systolic SMBP changed by ?6.9 mmHg (p = 0.004) at Months 5/6.ConclusionsImplementing an evidence-based multi-component BP-lowering intervention within existing congregate meal programs at senior centers serving minority and low-income communities is feasible, and early findings show promising evidence of effectiveness. This approach to cardiovascular risk reduction should be further tested for widespread adoption and impact.Registered on ClinicalTrials.gov NCT03993808 (June 21st, 2019)     

Left Ventricular Structural and Functional Alterations in Patients With Pheochromocytoma/Paraganglioma Before and After Surgery

ObjectivesThis study sought to evaluate left ventricular (LV) structure and function in pheochromocytoma and paraganglioma (PPGL) patients before and after curative surgery.BackgroundData on catecholamine-induced effects on LV structure and function in patients with PPGL are limited and conflicting.MethodsThe study evaluated 81 consecutive patients with a PPGL, among whom 66 were evaluated 12 months after tumor removal. Fifty patients matched for age, sex, hypertension presence, and blood pressure (BP) levels served as a control group (non-PPGL group). Echocardiography was employed to assess the LV mass index (LVMI), systolic function including speckle tracking echocardiography, and diastolic function.ResultsPatients with PPGL were characterized by higher LVMI (median 103 [interquartile range (IQR): 88 to 132] g/m² vs. median 94 [IQR: 74 to 106] g/m²; p = 0.006) and frequency of LV hypertrophy (44.4% vs. 24.0%; p = 0.018) compared with the non-PPGL group. Patients with PPGLs were characterized by lower global longitudinal strain (GLS) and early diastolic mitral annular velocity compared with patients in the non-PPGL group (median –17.2% [IQR: 15.6% to 18.9%] vs. median –19.3% [IQR: 17.7% to 20.6%]; p < 0.001; and median 11.1 [IQR: 8.3 to 13.0] cm/s vs. median 12.3 [IQR: 10.6 to 14.6] cm/s; p = 0.018, respectively). Presence of LV hypertrophy and GLS were independently associated with plasma free metanephrine concentrations. In operated patients, there were lower frequencies of LV hypertrophy (39.4% vs. 22.7%; p = 0.003), LVMI (median 98 [IQR: 85 to 115] g/m² vs. median 90 [IQR: 76 to 109] g/m²; p < 0.001), and the ratio of transmitral early diastolic velocity to early diastolic mitral annular velocity (median 6.8 [IQR: 5.5 to 8.6] vs. median 6.0 [IQR: 5.0 to 7.6]; p = 0.005) but higher values for GLS (median –17.4 [IQR: –15.8 to 19.1] vs. median −18.5 [IQR: –17.1 to 20.1] p < 0.001) after compared with before surgery.ConclusionsCatecholamine excess in patients with PPGLs can lead not only to LV hypertrophy, but also to impairment of systolic LV function and subclinical alterations of diastolic LV function, independently of BP levels. These structural and functional changes are reversible after surgical intervention.     

Starch digestibility modulation significantly improves glycemic variability in type 2 diabetic subjects: A pilot study

Background and aimsIn type 2 diabetes (T2D) patients, the reduction of glycemic variability and postprandial glucose excursions is essential to limit diabetes complications, beyond HbA1c level. This study aimed at determining whether increasing the content of Slowly Digestible Starch (SDS) in T2D patients’ diet could reduce postprandial hyperglycemia and glycemic variability compared with a conventional low-SDS diet.Methods and resultsFor this randomized cross-over pilot study, 8 subjects with T2D consumed a controlled diet for one week, containing starchy products high or low in SDS. Glycemic variability parameters were evaluated using a Continuous Glucose Monitoring System.Glycemic variability was significantly lower during High-SDS diet compared to Low-SDS diet for MAGE (Mean Amplitude of Glycemic Excursions, p < 0.01), SD (Standard Deviation, p < 0.05), and CV (Coefficient of Variation, p < 0.01). The TIR (Time In Range) [140–180 mg/dL[ was significantly higher during High-SDS diet (p < 0.0001) whereas TIRs ≥180 mg/dL were significantly lower during High-SDS diet. Post-meals tAUC (total Area Under the Curve) were significantly lower during High-SDS diet.ConclusionOne week of High-SDS Diet in T2D patients significantly improves glycemic variability and reduces postprandial glycemic excursions. Modulation of starch digestibility in the diet could be used as a simple nutritional tool in T2D patients to improve daily glycemic control.Registration numberin clinicaltrials.gov: NCT 03289494.     

Carotid artery intima-media thickness in adults receiving long-term home parenteral nutrition

Background and aimsNutrition regimen in parenteral nutrition (PN) patients allows for a control of diet components. This may affect the process of lipid deposition in the vascular wall and change the risk of atherosclerosis. This study aims to examine the effect of long-term PN in adults on carotid intima-media thickness.Methods and resultsThirty long-term PN patients (15 men and 15 women, mean age 64.7 ± 8.5 years) and thirty healthy volunteers (HV) (15 men and 15 women, mean age 64.9 ± 8.77 years) entered the study. Total amino acid and lipid formulation intake as well as duration of PN were calculated for PN patients. The common carotid artery intima-media thickness (CCA IMT) was examined in both groups.A lower CCA IMT (right/left mean: PN - 776 ± 121 vs HV - 848 ± 121 μm, p < 0.05; right/left maximum CCA IMT: PN - 935 ± 139 vs HV - 1024 ± 135 μm, p < 0.05) in PN patients was observed. A lower serum level of total (PN - 131.43 ± 43.12 vs HV - 209.2 ± 48.01 mg/dl, p < 0.05) and HDL (PN- 44.16 ± 12.45 vs HV - 72.57 ± 25.04 mg/dl, p < 0.05) cholesterol was reported in the PN patients. A correlation between patients’ age and CCA IMT was observed in the control group, but not in the PN patients (right/left mean CCA IMT - PN: r = 0.48, p-0.007 vs HV: p-0.073; right/left maximum CCA IMT – PN: r = 0.48, p-0.008, vs HV: p-0.073).ConclusionsLong term PN in adults is associated with lower CCA IMT. Long-term PN patients are a unique group in which carotid intima-media thickness does not correlate with the age.