Aortic stenting in the growing sheep causes aortic endothelial dysfunction but not hypertension: Clinical implications for coarctation repair

Stent implantation is the treatment of choice for adolescents and adults with aortic coarctation (CoAo). Despite excellent short-term results, 20%-40% of the patients develop arterial hypertension later in life, which was attributed to inappropriate response of the aortic baroreceptors to increased stiffness of the ascending aorta (ASAO), either congenital or induced by CoAo repair. In particular, it has been hypothesized that stent itself may cause or sustain hypertension. Therefore, we aimed to study the hemodynamic and structural impact following stent implantation in the normal aorta of a growing animal

Critical issues in the relationships between patient relatives and hospital staff: qualitative research based on focus group

In Italy the number of elderly patients is increasing and often a family member, also called primary caregiver (CG), assists them. The aim of this study is to describe the peculiar relationships between the family primary CG and the hospital staff, when an elderly patient is admitted to hospital, to demonstrate how this may affect his/her clinical management during the hospital stay and formulate new research projects and organizational rearrangements

Who should be screened for secondary causes of hypertension?

The case of a 34-year-old patient with uncontrolled hypertension is described in this article, together with the diagnostic path followed in order to make the diagnosis, that finally reveals an arteriovenous fistula due to an old kidney biopsy. Uncontrolled or resistant hypertension may be caused by unrecognized secondary hypertension: we revise the clinical and laboratory criteria for selecting hypertensive patients in whom to look for secondary hypertension through the most appropriate diagnostic work up. A synthesis of the main causes of secondary hypertension is also provided in the discussion

Genetic modifiers of Duchenne muscular dystrophy and dilated cardiomyopathy

OBJECTIVE: Dilated cardiomyopathy (DCM) is a major complication and leading cause of death in Duchenne muscular dystrophy (DMD). DCM onset is variable, suggesting modifier effects of genetic or environmental factors. We aimed to determine if polymorphisms previously associated with age at loss of independent ambulation (LoA) in DMD (rs28357094 in the SPP1 promoter, rs10880 and the VTTT/IAAM haplotype in LTBP4) also modify DCM onset. METHODS: A multicentric cohort of 178 DMD patients was genotyped by TaqMan assays. We performed a time-to-event analysis of DCM onset, with age as time variable, and finding of left ventricular ejection fraction 70 mL/m2 as event (confirmed by a previous normal exam < 12 months prior); DCM-free patients were censored at the age of last echocardiographic follow-up. RESULTS: Patients were followed up to an average age of 15.9 \ub1 6.7 years. Seventy-one/178 patients developed DCM, and median age at onset was 20.0 years. Glucocorticoid corticosteroid treatment (n = 88 untreated; n = 75 treated; n = 15 unknown) did not have a significant independent effect on DCM onset. Cardiological medications were not administered before DCM onset in this population. We observed trends towards a protective effect of the dominant G allele at SPP1 rs28357094 and recessive T allele at LTBP4 rs10880, which was statistically significant in steroid-treated patients for LTBP4 rs10880 (< 50% T/T patients developing DCM during follow-up [n = 13]; median DCM onset 17.6 years for C/C-C/T, log-rank p = 0.027). CONCLUSIONS: We report a putative protective effect of DMD genetic modifiers on the development of cardiac complications, that might aid in risk stratification if confirmed in independent cohorts

Clustering of risk factors in hypertensive insulin-dependent diabetics with high sodium-lithium countertransport

Clustering of risk factors in hypertensive insulin-dependent diabetics with high sodium-lithium countertransport. Diabetic nephropathy is more common in patients with a positive family history of hypertension and with elevated red blood cell sodium-lithium countertransport, a marker of risk for essential hypertension. To evaluate whether there is a relationship between this cation transport system and indicators of risk of renal and cardiovascular complications in diabetic patients before the development of clinical proteinuria, we studied 31 type 1 (insulin-dependent) diabetic patients with arterial hypertension, without clinical proteinuria and 12 normotensive normoalbuminuric diabetic patients. Sodium-lithium countertransport activity was significantly higher in hypertensive patients (0.43 ± 0.03 mmol/1 RBC x hr) than in normotensive patients (0.23 ± 0.03; P < 0.001). To better explore the nature of the association between this transport system and arterial hypertension, hypertensive patients were divided in two groups, with high (>0.41 mmol/1 RBC x hr) or normal (<0.41) sodium-lithium countertransport activity. The two groups of hypertensive diabetics were similar in age, sex, body mass index and blood pressure levels. Hypertensive patients with elevated rates of sodium-lithium counter-transport compared with those with normal sodium-lithium counter-transport activity showed elevated glomerular filtration rate (130 ± 4 ml/min/1.73 m2 vs. 122 ± 3; P < 0.05), albumin excretion rate (median 26 /Lcg/min vs. 11; P < 0.001), higher fractional proximal sodium reabsorption (74 ± 1.2% vs. 71.6 ± 0.9; P < 0.01), exchangeable sodium pool (2937 ± 62 mmol/1.73 m2 vs. 2767 ± 56; P < 0.01), larger kidney volume (317 ± 7 ml/1.73 m2 vs. 270 ± 8; P < 0.05) and left ventricular mass index (122 ± 4 g/m2 vs. 107 ± 5; P < 0.05). Hypertensive patients with normal sodium-lithium countertransport activity had renal parameters similar to normotensive diabetic patients, except higher left ventricular mass index and kidney volume. Hypertensive diabetic patients with elevated sodium-lithium countertransport activity also had higher levels of plasma triglycerides, lower plasma HDL-cholesterol and impaired insulin sensitivity (assessed by euglyce-mic insulin-glucose clamp) compared with the other two groups. In conclusion, renal, cardiac and metabolic abnormalities are prominent in hypertensive type 1 (insulin-dependent) diabetic patients with higher sodium-lithium countertransport

In-hospital percentage BNP reduction is highly predictive for adverse events in patients admitted for acute heart failure: the Italian RED Study

Introduction: Our aim was to evaluate the role of B-type natriuretic peptide (BNP) percentage variations at 24 hours and at discharge compared to its value at admission in order to demonstrate its predictive value for outcomes in patients with acute decompensated heart failure (ADHF). Methods: This was a multicenter Italian (8 centers) observational study (Italian Research Emergency Department: RED). 287 patients with ADHF were studied through physical exams, lab tests, chest X Ray, electrocardiograms (ECGs) and BNP measurements, performed at admission, at 24 hours, and at discharge. Follow up was performed 180 days after hospital discharge. Logistic regression analysis was used to estimate odds ratios (OR) for the various subgroups created. For all comparisons, a P value 46% at discharge had an area under curve (AUC) of 0.70 (P 300 pg/mL. A BNP reduction of 25.9% after 24 hours had an AUC at ROC curve of 0.64 for predicting adverse events (P 46% was 4.775 (95% confidence interval (CI) 1.76 - 12.83, P 300 pg/mL and whose percentage decrease at discharge was 46% was 9.614 (CI 4.51 - 20.47, P 46% at hospital discharge compared to the admission levels coupled with a BNP absolute value < 300 pg/mL seems to be a very powerful negative prognostic value for future cardiovascular outcomes in patients hospitalized with ADHF

Syncope and sudden death from the emergency physician's perspective: is there room for new biomarkers?

Syncope is a transient loss of consciousness due to temporary global cerebral hypoperfusion characterized by rapid onset, short duration, and spontaneous complete recovery. Syncope represents 1-2% of emergency department (ED) visits and is coupled with a high risk for mortality, prolonged hospital admission, and immediate false diagnosis. Many patients who present to the ED with aspecific symptoms are mainly hospitalized because of diagnostic uncertainty. It is always very important to immediately distinguish syncope of cardiac and non-cardiac origins. Cardiac syncope has higher risk for mortality especially for sudden cardiac death, while non-cardiac one shows risk of repeated events of syncope with poor quality of life. Sudden cardiac death is defined as rapid and unexpected natural death due to cardiac etiology. Researchers from the GREAT Network hypothesized to evaluate some novel biomarkers in order to test acute cardiac condition that can suggest the presence of heart structural diseases, heart failure, and electrical disorders. The primary objective of this study is to test the diagnostic performance from patient history, clinical judgment, and novel biomarkers in the diagnosis of cardiac syncope in patients admitted to the ED. The trial is designed as a prospective international multicenter observational study accounting for 730 patients aged over 40 admitted to the ED with syncope within the last 12 h. A multimarker approach combining markers of different origin and mode of relapse, should add diagnostic information to correctly identify the cardiac conditions and to therefore be pertinent in the early diagnosis of cardiac syncope and in the prediction of cardiac events including sudden death. Future data should be needed to confirm the hypothesis presented here

Distribution of Exonic Variants in Glycogen Synthesis and Catabolism Genes in Late Onset Pompe Disease (LOPD)

Pompe disease (PD) is a monogenic autosomal recessive disorder caused by biallelic pathogenic variants of the GAA gene encoding lysosomal alpha-glucosidase; its loss causes glycogen storage in lysosomes, mainly in the muscular tissue. The genotype-phenotype correlation has been extensively discussed, and caution is recommended when interpreting the clinical significance of any mutation in a single patient. As there is no evidence that environmental factors can modulate the phenotype, the observed clinical variability in PD suggests that genetic variants other than pathogenic GAA mutations influence the mechanisms of muscle damage/repair and the overall clinical picture. Genes encoding proteins involved in glycogen synthesis and catabolism may represent excellent candidates as phenotypic modifiers of PD. The genes analyzed for glycogen synthesis included UGP2, glycogenin (GYG1-muscle, GYG2, and other tissues), glycogen synthase (GYS1-muscle and GYS2-liver), GBE1, EPM2A, NHLRC1, GSK3A, and GSK3B. The only enzyme involved in glycogen catabolism in lysosomes is alpha-glucosidase, which is encoded by GAA, while two cytoplasmic enzymes, phosphorylase (PYGB-brain, PGL-liver, and PYGM-muscle) and glycogen debranching (AGL) are needed to obtain glucose 1-phosphate or free glucose. Here, we report the potentially relevant variants in genes related to glycogen synthesis and catabolism, identified by whole exome sequencing in a group of 30 patients with late-onset Pompe disease (LOPD). In our exploratory analysis, we observed a reduced number of variants in the genes expressed in muscles versus the genes expressed in other tissues, but we did not find a single variant that strongly affected the phenotype. From our work, it also appears that the current clinical scores used in LOPD do not describe muscle impairment with enough qualitative/quantitative details to correlate it with genes that, even with a slightly reduced function due to genetic variants, impact the phenotype

Quantitative value of aldosterone-renin ratio for detection of aldosterone-producing adenoma: The Aldosterone-Renin Ratio for Primary Aldosteronism (AQUARR) study

Background Current guidelines recommend use of the aldosterone\u2010renin ratio (ARR) for the case detection of primary aldosteronism followed by confirmatory tests to exclude false\u2010positive results from further diagnostic workup. We investigated the hypothesis that this could be unnecessary in patients with a high ARR value if the quantitative information carried by the ARR is taken into due consideration. Methods and Results We interrogated 2 large data sets of prospectively collected patients studied with the same predefined protocol, which included the captopril challenge test. We used an unambiguous diagnosis of aldosterone\u2010producing adenoma as reference index. We also assessed whether the post\u2010captopril ARR and plasma aldosterone concentration fall furnished a diagnostic gain over baseline ARR values. We found that the false\u2010positive rate fell exponentially, and, conversely, the specificity increased with rising ARR values. At receiver operating characteristics curves and diagnostic odds ratio analysis, the high baseline ARR values implied very high positive likelihood ratio and diagnostic odds ratio values. The baseline and post\u2010captopril ARR showed similar diagnostic accuracy (area under the receiver operating characteristics curve) in both the exploratory and validation cohorts, indicating lack of diagnostic gain with this confirmatory test (between\u2010area under the curve difference, 0.005; 95% CI, 120.031 to 0.040; P=0.7 for comparison, and 0.05; 95% CI, 120.061 to 0.064; P=0.051 for comparison, respectively). Conclusions These results indicate that the ARR conveys key quantitative information that, if properly used, can simplify the diagnostic workup, resulting in saving of money and resources. This can offer the chance of diagnosis and ensuing adrenalectomy to a larger number of hypertensive patients, ultimately resulting in better control of blood pressure