Transcatheter Valve Repair for Patients With Mitral Regurgitation: 30-Day Results of the CLASP Study

ObjectivesThe authors report the procedural and 30-day results of the PASCAL Transcatheter Valve Repair System (Edwards Lifesciences, Irvine, California) in patients with mitral regurgitation (MR) enrolled in the multicenter, prospective, single-arm CLASP study.BackgroundSevere MR may lead to symptoms, impaired quality of life, and reduced functional capacity when untreated.MethodsEligible patients had grade 3+ or 4+ MR despite optimal medical therapy and were deemed appropriate for the study by the local heart team. All outcomes were assessed through 30 days post-procedure. Major adverse events (MAEs) were adjudicated by an independent clinical events committee, and echocardiographic images were assessed by a core laboratory. The primary safety endpoint was the rate of MAEs at 30 days.ResultsBetween June 2017 and September 2018, 62 patients with grade 3+ or 4+ MR were enrolled. The mean age was 76.5 years, and 51.6% of patients were in New York Heart Association functional class III or IV, with 56% functional, 36% degenerative, and 8% mixed MR etiology. At 30 days, the MAE rate was 6.5%, with an all-cause mortality rate of 1.6% and no occurrence of stroke; 98% had MR grade ≤2+, with 86% with MR grade ≤1+ (p < 0.0001); and 85% were in New York Heart Association functional class I or II (p < 0.0001). Six-minute walk distance improved by 36 m (p = 0.0018), and Kansas City Cardiomyopathy Questionnaire and EQ-5D scores improved by 17 (p < 0.0001) and 10 (p = 0.0004) points, respectively.ConclusionsThe PASCAL repair system showed feasibility and acceptable safety in the treatment of patients with grade 3+ or 4+ MR. MR severity, irrespective of etiology, was significantly reduced and accompanied by clinically and statistically significant improvements in functional status, exercise capacity, and quality of life. (The CLASP Study Edwards PASCAL Transcatheter Mitral Valve Repair System Study; NCT03170349)     

Obestatin and ghrelin levels in obese children and adolescents before and after reduction of overweight

Objectives Obestatin and ghrelin, which are derived from the same gene, are observed to have opposite effects on weight status. The aims of this study were to compare obestatin concentrations in obese and normal‐weight children and to analyse the effect of weight loss on obestatin and ghrelin levels. Methods We examined anthropometrical markers and fasting serum obestatin, ghrelin, leptin, glucose and insulin concentrations in 44 obese children (mean age 11·2 years) before and after participating in a 1‐year outpatient obesity intervention programme based on a high‐carbohydrate, fat‐reduced diet and increased physical activity. Additionally, total ghrelin, obestatin and leptin levels were determined in 22 normal‐weight healthy children of similar age, gender and pubertal stage. Results Obestatin and leptin concentrations were significantly (P < 0·001) higher and ghrelin concentrations were significantly (P < 0·001) lower in obese children compared to nonobese children. In contrast to the 13 children without weight loss, substantial weight loss in 31 children led to a significant (P = 0·007) increase in obestatin and to a significant (P < 0·05) decrease in leptin and insulin concentrations, while ghrelin concentrations did not change significantly. Children with substantial weight loss demonstrated significantly (P = 0·009) lower obestatin and a tendency (P = 0·064) to higher ghrelin concentrations at baseline. Changes in insulin were not related to changes in ghrelin or obestatin. Conclusion The increase in obestatin and the decrease in ghrelin in obese children point towards an adaptation process of weight status. Weight reduction due to a long‐term lifestyle intervention resulted in an increase in obestatin levels.     

Diffuse esophageal spasm: not diffuse but distal esophageal spasm (DES)

Diffuse esophageal spasm is an uncommon motility disorder that is found in less than 5% of patients undergoing esophageal motility testing for dysphagia. It is defined manometrically by the presence of 20% or more simultaneous contractions in the distal esophageal body with normal peristalsis. This motility abnormality has been traditionally identified as occurring primarily in the smooth muscle portion of the distal esophagus yet, the term diffuse persists in the medical literature to identify DES. The aim of our study was to assess the diffuse or limited nature of this entity by evaluating the prevalence of simultaneous contractions in both proximal and distal esophagus in patients with DES. We reviewed esophageal motility tracings of 53 consecutive patients (32 F, 21 M) with DES and compared them with 53 age-matched patients with manometric normal studies. In the distal esophagus we found 195 simultaneous contractions (37% of swallows) with a median of 3 and range of 2–7 per patient. Of the 53 patients with DES a total of 13 simultaneous contractions (2% of swallows) occurred in the proximal esophagus with only 3 (5.6%) of the 53 patients having 2 or more simultaneous contractions in 10 swallows. None of the patients with normal manometry showed more than one simultaneous contraction in either proximal or distal esophagus. In conclusion, these findings suggest that the term diffuse esophageal spasm is a misnomer and the DES is more appropriately described as distal esophageal spasm.     

Duration of antiretroviral therapy among people living with HIV and incidence of hypertension in Ghana

Understanding the differential rates of incident hypertension among People Living with HIV (PLWH) based of duration of exposure to combination antiretroviral therapy (cART) may provide insights into the pathogenesis of hypertension in this population. Utilizing the dataset of a prospective study conducted at a Ghanaian tertiary medical center, we evaluated factors associated with incident hypertension among PLWH previously naïve to cART before study enrollment (cART newly prescribed group, n = 221) versus PLWH established on cART for at least a year (cART established group, n = 212). New‐onset hypertension was diagnosed as clinic BP > 140/90 mmHg on two separate clinic visits over 12‐month follow‐up. Cox proportional hazards regression models were used to assess factors associated with incident hypertension. Mean age of new versus cART established was 41.1 ± 8.2 versus 45.1 ± 8.6 years (p < .001), with more women in the cART established group (68.3 vs. 82%, p = .0009). There were 105 (24.3%) episodes of incident hypertension over 328 person‐years follow‐up (PYFU), incidence rate of 320.1 (95% CI: 263.1‐385.9)/1000 PYFU, with higher rates in new versus cART established (476.6/1000 PYFU vs. 222.8/1000 PYFU, p = 0.0002). Overall, age by increasing decile (aHR 0.76; 95% CI: 0.59‐0.98), log HIV‐1 viral load (aHR 1.16; 1.04‐1.35), and use of tenofovir (aHR 1.66; 1.04‐2.64) were associated with incident hypertension. While CD4 counts, age, BMI, pre‐diabetes, and urban/peri‐urban residency were independently associated with hypertension in the cART established group; no independent predictors were identified among the cART newly prescribed group. Further studies to explore the potential mechanisms underlying incidence of hypertension in PLWH are warranted.     

Comparative analysis of portal cell infiltrates in antimitochondrial autoantibody-positive versus antimitochondrial autoantibody-negative primary biliary cirrhosis

Substantial evidence supports dysregulated B-cell immune responses in patients with primary biliary cirrhosis (PBC), including the presence of serum antimitochondrial antibodies (AMAs). However, recent reports from murine models of PBC suggest that B cells may also provide regulatory function, and indeed the absence of B cells in such models leads to exacerbation of disease. The vast majority of patients with PBC have readily detectable AMAs, but a minority (<5%) are AMA negative (AMA(-)), even with recombinant diagnostic technology. This issue prompted us to examine the nature of B-cell infiltrates surrounding the portal areas in AMA-positive (AMA(+)) and AMA(-) patients, because they display indistinguishable clinical features. Of importance was the finding that the degree of bile duct damage around the portal areas was significantly milder in AMA(+) PBC than those observed in AMA(-) PBC patients. The portal areas from AMA(-) patients had a significant increase of cluster of differentiation (CD)5(+) cells infiltrating the ductal regions, and the levels of B-cell infiltrates were worse in the early phase of bile duct damage. The frequency of positive portal areas and the magnitude of CD5(+) and CD20(+) cellular infiltrates within areas of ductal invasion is associated with the first evidence of damage of biliary duct epithelia, but becomes reduced in the ductopenia stage, with the exception of CD5(+) cells, which remain sustained and predominate over CD20(+) cells. CONCLUSION: Our data suggest a putative role of B-cell autoimmunity in regulating the portal destruction characteristic of PBC.