Determinants of left ventricular mechanical dyssynchrony in patients submitted to myocardial perfusion imaging: A cardiac CZT study

Background

An interaction between coronary anatomy, myocardial perfusion, and left ventricular (LV) functional parameters in the development of mechanical LV dyssynchrony (LVD) has been suggested. This study examined the correlates of LVD in a large sample size of patients with known or suspected coronary artery disease (CAD) using cadmium-zinc-telluride camera.

Methods

Six-hundred and fifty-seven consecutive patients who underwent myocardial perfusion imaging (MPI) and coronary angiography were included. Coronary stenosis >70% was considered significant. LV perfusion and functional parameters were computed from MPI images. The presence of significant LVD was evaluated by phase standard deviation and histogram bandwidth.

Results

415/657 (63%) patients had significant CAD. LVD was present in 247 (38%) patients and was associated with the presence of a higher CAD burden (P < .001), more impaired measures of LV perfusion (P < .001), contractile function (P < .001), and larger LV volumes (P < .001). By multivariate analysis, the LV end-systolic volume index (P < .001) and ischemic burden (P < .001) were the strongest predictors of LVD independent of CAD extent and LV systolic dysfunction.

Conclusions

LVD is frequent in patients undergoing MPI for suspected or known CAD. Its presence is independent of CAD burden and LV systolic dysfunction, but is dependent on the presence of myocardial perfusion abnormalities and LV end-systolic volume.

     

Impact of aging on cardiac sympathetic innervation measured by <Superscript>123</Superscript>I-mIBG imaging in patients with systolic heart failure

Purpose

Sympathetic nervous system (SNS) hyperactivity is a salient characteristic of chronic heart failure (HF) and contributes to the progression of the disease. Iodine-123 meta-iodobenzylguanidine (¹²³I-mIBG) imaging has been successfully used to assess cardiac SNS activity in HF patients and to predict prognosis. Importantly, SNS hyperactivity characterizes also physiological ageing, and there is conflicting evidence on cardiac ¹²³I-mIBG uptake in healthy elderly subjects compared to adults. However, little data are available on the impact of ageing on cardiac sympathetic nerve activity assessed by ¹²³I-mIBG scintigraphy, in patients with HF.

Methods and results

We studied 180 HF patients (age?=?66.1?±?10.5 years [yrs]), left ventricular ejection fraction (LVEF?=?30.6?±?6.3 %) undergoing cardiac ¹²³I-mIBG imaging. Early and late heart to mediastinum (H/M) ratios and washout rate were calculated in all patients. Demographic, clinical, and echocardiographic data were also collected. Our study population consisted of 53 patients aged >75 years (age?=?77.7?±?4.0 year), 67 patients aged 62–72 years (age?=?67.9?±?3.2 years) and 60 patients aged ≤61 year (age?=?53.9?±?5.6 years). In elderly patients, both early and late H/M ratios were significantly lower compared to younger patients (p?<?0.05). By multivariate analysis, H/M ratios (both early and late) and washout rate were significantly correlated with LVEF and age.

Conclusions

Our data indicate that, in a population of HF patients, there is an independent age-related effect on cardiac SNS innervation assessed by ¹²³I-mIBG imaging. This finding suggests that cardiac ¹²³I-mIBG uptake in patients with HF might be affected by patient age.

     

Estimated GFR for Living Kidney Donor Evaluation

All living kidney donor candidates undergo evaluation of GFR. Guidelines recommend measured GFR (mGFR), using either an endogenous filtration marker or creatinine clearance, rather than estimated GFR (eGFR), but measurement methods are difficult, time consuming and costly. We investigated whether GFR estimated from serum creatinine (eGFRcr) with or without sequential cystatin C is sufficiently accurate to identify donor candidates with high probability that mGFR is above or below thresholds for clinical decision making. We combined the pretest probability for mGFR thresholds <60, <70, ≥80, and ≥90 mL/min per 1.73 m² based on demographic characteristics (from the National Health and Nutrition Examination Survey) with test performance of eGFR (categorical likelihood ratios from the Chronic Kidney Disease Epidemiology Collaboration) to compute posttest probabilities. Using data from the Scientific Registry of Transplant Recipients, 53% of recent living donors had predonation eGFRcr high enough to ensure ≥95% probability that predonation mGFR was ≥90 mL/min per 1.73 m², suggesting that mGFR may not be necessary in a large proportion of donor candidates. We developed a Web‐based application to compute the probability, based on eGFR, that mGFR for a donor candidate is above or below a range of thresholds useful in living donor evaluation and selection.     

Efficacy of Bariatric Surgery in Type 2 Diabetes Mellitus Remission: the Role of Mini Gastric Bypass/One Anastomosis Gastric Bypass and Sleeve Gastrectomy at 1 Year of Follow-up. A European survey

Background

A retrospective study was undertaken to define the efficacy of both mini gastric bypass or one anastomosis gastric bypass (MGB/OAGB) and sleeve gastrectomy (SG) in type 2 diabetes mellitus (T2DM) remission in morbidly obese patients (pts).

Methods

Eight European centers were involved in this survey. T2DM was preoperatively diagnosed in 313/3252 pts (9.62 %). In 175/313 patients, 55.9 % underwent MGB/OAGB, while in 138/313 patients, 44.1 % received SG between January 2006 and December 2014.

Results

Two hundred six out of 313 (63.7 %) pts reached 1 year of follow-up. The mean body mass index (BMI) for MGB/OAGB pts was 33.1?±?6.6, and the mean BMI for SG pts was 35.9?±?5.9 (p?<?0.001). Eighty-two out of 96 (85.4 %) MGB/OAGB pts vs. 67/110 (60.9 %) SG pts are in remission (p?<?0.001). No correlation was found in the % change vs. baseline values for hemoglobin A1c (HbA1c) and fasting plasma glucose (FPG) in relation to BMI reduction, for both MGB/OAGB or SG (ΔFPG 0.7 and ΔHbA1c 0.4 for MGB/OAGB; ΔFPG 0.7 and ΔHbA1c 0.1 for SG). At multivariate analysis, high baseline HbA1c [odds ratio (OR)?=?0.623, 95 % confidence interval (CI) 0.419–0.925, p?=?0.01], preoperative consumption of insulin or oral antidiabetic agents (OR?=?0.256, 95 % CI 0.137–0.478, p?=?<0.001), and T2DM duration >10 years (OR?=?0.752, 95 % CI 0.512–0.976, p?=?0.01) were negative predictors whereas MGB/OAGB resulted as a positive predictor (OR?=?3.888, 95 % CI 1.654–9.143, p?=?0.002) of diabetes remission.

Conclusions

A significant BMI decrease and T2DM remission unrelated from weight loss were recorded for both procedures if compared to baseline values. At univariate and multivariate analyses, MGB/OAGB seems to outperform significantly SG. Four independent variables able to influence T2DM remission at 12 months have been identified.

     

Assessment of in vivo fetal growth and placental vascular function in a novel intrauterine growth restriction model of progressive uterine artery occlusion in guinea pigs

Key points

• Intrauterine growth restriction (IUGR) is associated with short‐ and long‐term detrimental cardiometabolic effects.
• Mice and rats are commonly used to assess IUGR, but differences in placental and fetal developmental physiology relative to those in humans highlight the need for alternative small animal IUGR models.
• We developed a guinea pig IUGR model by gradual occlusion of uterine arteries by ameroid constrictor implantation. In this model, reduced uterine blood flow was associated with IUGR, allowing in vivo assessment of fetal growth trajectory and umbilico‐placental vascular function in conscious animals.
• The intervention induces placental vascular dysfunction and remodelling, as well as altered fetal abdominal growth resulting in an asymmetric IUGR and preserved brain growth.

Abstract

Intra‐uterine growth restriction (IUGR) is associated with short and long‐term metabolic and cardiovascular alterations. Mice and rats have been extensively used to study the effects of IUGR, but there are notable differences in fetal and placental physiology relative to those of humans that argue for alternative animal models. This study proposes that gradual occlusion of uterine arteries from mid‐gestation in pregnant guinea pigs produces a novel model to better assess human IUGR. Fetal biometry and in vivo placental vascular function were followed by sonography and Doppler of control pregnant guinea pigs and sows submitted to surgical placement of ameroid constrictors in both uterine arteries (IUGR) at mid‐gestation (35 days). The ameroid constrictors induced a reduction in the fetal abdominal circumference growth rate (0.205 cm day⁻¹) compared to control (0.241 cm day⁻¹, P < 0.001) without affecting biparietal diameter growth. Umbilical artery pulsatility and resistance indexes at 10 and 20 days after surgery were significantly higher in IUGR animals than controls (P < 0.01). These effects were associated with a decrease in the relative luminal area of placental chorionic arteries (21.3 ± 2.2% vs. 33.2 ± 2.7%, P < 0.01) in IUGR sows at near term. Uterine artery intervention reduced fetal (∼30%), placental (∼20%) and liver (∼50%) weights (P < 0.05), with an increased brain to liver ratio (P < 0.001) relative to the control group. These data demonstrate that the ameroid constrictor implantations in uterine arteries in pregnant guinea pigs lead to placental vascular dysfunction and altered fetal growth that induces asymmetric IUGR.     

Chimerism and tetragametic chimerism in humans: implications in autoimmunity, allorecognition and tolerance

The presence of cells or tissues from two individuals, chimeras, or the presence of cells and tissues that include the gonads, tetragametic chimerism can be detected by the analysis of cytogenetics and analysis of polymorphic genetic markers, using patterns of pedigree inheritance. These methodologies include determination of sex chromosomes, major histocompatibility complex (MHC) polymorphisms and panels of short tandem repeats (STRs) that include mitochondrial DNA markers. Studies routinely involve cases of temporal chimerism in blood transfusion, or following allotransplantation to measure the outcome of the organ, lymphopoietic tissues or bone marrow grafts. Demonstration of persistent chimerism is usually discovered in cases of inter-sexuality due to fusion of fraternal twins or in cases of fusion of embryos with demonstrable allogeneic monoclonality of blood which, excluded maternity or paternity when blood alone is used as the source of DNA. In single pregnancies it is possible to produce two kinds of microchimerism: feto-maternal and materno-fetal, but in cases of fraternal twin pregnancies it is possible to identify three different kinds which are related to cases of vanishing twins that can be identified during pregnancy by imaging procedures; (1) hematopoietic, (2) gonadal, and (3) freemartins when the twins have different sex and the individual born is a female with either gonadal or both gonadal and hematopoietic tissues. Fraternal twin pregnancies can also produce fusion of embryos. Such cases could be of different sex presenting with inter-sexuality or in same sex twins. One of such cases, the best studied, showed evidence of chimerism and tetragametism. In this regard, the case was studied because of disputed maternity of two of her three children. All tissues studied, except for the blood, demonstrated four genetic components but only two in her blood of four possible showed allogeneic monoclonality consistent with the interpretation that her blood originated from one hematopoietic stem cell. Also, microchimerism, due to traffic of cells via materno-fetal or feto-maternal has been prompted by reports of their potential association with the development of autoimmune disorders including systemic lupus erythematosus (SLE) and systemic sclerosis, and in allotransplantation. In addition, their relevance of chimerism in the positive and negative selection of T cells in the thymus has not been addressed. T lymphocytes play a central role in controlling the acquired immune response and furthermore serve as crucial effector cells through antigen specific cytotoxic activity and the production of soluble mediators. Central tolerance is established by the repertoire selection of immature T lymphocytes in the thymus, avoiding the generation of autoreactive T cells. Expression of chimeric antigens in the thymus could modify the generation of specific T cell clones in chimeric subjects and these mechanisms could be important in the induction of central tolerance against foreign antigens important in allo-transplantation. In this review, we discuss the genetics of chimerism and tetragametism and its potential role in thymic selection and the relevance in allotransplantation and autoimmune disorders. This review is dedicated to the memory of Robert A. Good, MD, PhD, an outstanding physician and scientist, one discoverer of the functions of the Thymus in immunobiology and the pioneer of human bone marrow allotransplantation. Presented at the First Robert A Good Society Symposium, St. Petersburg, FL 2006.     

Gender-specific association of the PTPN22 C1858T polymorphism with achalasia

The protein tyrosine phosphatase N22 (PTPN22) gene encodes a lymphoid-specific phosphatase (LYP), a downregulator of T-cell activation. Because a functional PTPN22 polymorphism, C1858T, has been found to be associated with different autoimmune diseases, we aimed to elucidate the role of this variant in predisposition to achalasia. We performed a case-control study with 231 nonrelated Spanish patients of white ethnicity diagnosed with achalasia and in 554 healthy control subjects, all genotyped for PTPN22 C1858T using TaqMan chemistry. The frequency of the 1858T allele was higher in the achalasia patients than in the healthy controls (carriers of allele T vs CC: OR = 1.38, 95% confidence interval [95% CI] 0.88-2.16, p = 0.13). Moreover a different genotype distribution was found between female and male patients (carriers of allele T vs CC: OR = 2.06, 95% CI 0.96-4.42, p = 0.04) and also between female patients and controls (OR = 1.94, 95% CI 1.12-3.36, p = 0.01), but not between male patients and controls (OR = 0.94, 95% CI 0.50-1.77, p = 0.85). We conclude that the PTPN22 1858T allele is a susceptibility factor for Spanish women with achalasia.     

Black Hispanics have a worse cardiovascular risk profile than mixed Hispanics in Venezuela

In order to characterize components of the metabolic syndrome (MS) in Venezuelan black Hispanics and compare these metabolic abnormalities with those found in the predominant mixed Hispanic population, 2336 mixed Hispanics (69% women) and 281 black Hispanics (60% women), aged 20-78 years, without prior history of diabetes and/or cardiovascular disease were evaluated in a population-based study in Zulia State, Venezuela. Blood pressure (BP), waist circumference, as well as fasting insulin, fasting blood glucose (FBG), triglycerides (TG) and high-density lipoprotein cholesterol (HDL-C) levels were measured. The criteria proposed by the National Cholesterol Education Program/Adult Treatment Panel III (NCEP/ATP III) to identify those with metabolic abnormalities were used. We found that black Hispanics showed higher frequency of age-adjusted elevated BP than mixed Hispanics in both men (66.9% vs. 52.3%, p < 0.01) and women (39.3% vs. 30.4%, p < 0.05). In men, elevated FBG was also more frequent in black Hispanics (32.7%) than in mixed Hispanics (22.3%), despite the lack of significant differences in fasting insulin, HOMA-insulin resistance and HOMA-beta cell function values. In women low HDL-C and higher abdominal obesity were more common in black Hispanics (71.8% and 54.1%, respectively) than in mixed Hispanics (56.2% and 44.5%, respectively), despite the greater frequency of high TG in mixed Hispanics (22.6%) when compared to black Hispanics (13.3%). Furthermore, in logistic regression analysis black Hispanic race was independently associated with higher risk for hypertension, fasting hyperglycemia, and low HDL-C. These results suggest that black Hispanics have worse cardiovascular risk profile than mixed Hispanics in Zulia State, with higher BP, higher FBG, more abdominal obesity, and lower HDL-C. Identification and intervention of these high-risk subjects are important strategies for diabetes and cardiovascular disease prevention in Venezuela.