Autosomal dominant and autosomal recessive polycystic kidney disease: hypertension and secondary cardiovascular effect in children.

Autosomal dominant (ADPKD) and autosomal recessive (ARPKD) polycystic kidney disease are the most widely known cystic kidney diseases. They are significantly different from each other in terms of genetics and clinical manifestations. Hypertension is one of the main symptoms in both diseases, but the age of onset and secondary cardiovascular complications are significantly different. Most ARPKD children are hypertensive in the first year of life and need high doses of hypertensive drugs. ADPKD patients with a very early onset of the disease (VEOADPKD) develop hypertension similarly to patients with ARPKD. Conversely, a significantly lower percentage of patients with classic forms of ADPKD develops hypertension during childhood, although probably more than originally thought. Data published in the past decades show that about 20%-30% of ADPKD children are hypertensive. Development of hypertension before 35 years of age is a known risk factor for more severe disease in adulthood. The consequences of hypertension on cardiac geometry and function are not well documented in ARPKD due to the rarity of the disease, the difficulties in collecting homogeneous data, and differences in the type of parameters evaluated in different studies. Overall, left ventricular hypertrophy (LVH) has been reported in 20%-30% of patients and does not always correlate with hypertension. Conversely, cardiac geometry and cardiac function are preserved in the vast majority of hypertensive ADPKD children, even in patients with faster decline of kidney function. This is probably related to delayed onset of hypertension in ADPKD, compared to ARPKD. Systematic screening of hypertension and monitoring secondary cardiovascular damage during childhood allows initiating and adapting antihypertensive treatment early in the course of the disease, and may limit disease burden later in adulthood.

Long-term assessment of clinical outcomes and disease progression in patients with corrected Tetralogy of Fallot.

OBJECTIVE: Understanding changes of right ventricular (RV) geometry and function in repaired Tetralogy of Fallot (rToF) patients can improve decision-making for pulmonary valve replacement. Therefore, we aimed to assess the magnitude and clinical correlations of RV changes in rToF patients. PATIENTS AND METHODS: Clinical and MRI data of rToF patients who underwent repeated cardiac magnetic resonance imaging (MRI) at two centers between December 2003 and September 2020 were analyzed together with anatomical factors, including RV outflow tract obstruction, pulmonary artery branch stenosis, and tricuspid regurgitation. Adverse cardiac events and/or NYHA class worsening were documented and correlated with MRI changes. QRS length was reported at each MRI. RESULTS: Two-hundred-and-nineteen rToF patients (53% males, aged 20.2 ± 10.1 years) were enrolled. An increase of ventricular dimensions, except LVEDVi, and worsening of right and left ejection fractions were found over an average period of 5 years of follow-up. These changes were statistically significant but within 10% of the initial value. No significant changes were reported on a year-to-year basis, except in a small group of patients (6%) in whom no predictive factors were identified. Despite similar RV dimensions at the first examination, younger patients had a higher RV ejection fraction and a different annual rate of change of ventricular dimensions compared to older ones. Patients with arrhythmias (20%) were more frequently older and had larger RV dimensions but showed no significant correlations with MRI changes/years. CONCLUSIONS:  Changes in RV dimensions and function occur rarely and very slowly in rToF patients. A small percentage of patients experience a significant worsening in a short time interval without any recognized risk factors. Arrhythmias appear to occur in a small percentage of cases in the late follow-up.

Early left ventricular abnormality/dysfunction in obese children affected by NAFLD.

BACKGROUND AND AIMS: Although it is generally accepted that non alcoholic fatty liver disease (NAFLD) is linked to increased risk of cardiovascular disease, the presence of abnormalities in cardiac function among NAFLD children is limited and controversial. Aim of the study was to detect cardiac abnormalities/dysfunction in a paediatric population of NAFLD. METHODS AND RESULTS: Anthropometric, laboratory, cardiovascular fitness, 24 h blood pressure monitoring and Doppler echocardiography parameters were obtained in 50 untreated children (37 males; mean age 12.2 + 2.5) with biopsy-proven NAFLD. Abnormalities in both cardiac function and geometry could be identified in the whole study population: prevalence of about 35% in left ventricular hypertrophy, 14% of concentric remodelling and 16% of left atrial dilatation. Furthermore children with NAFLD (NAS score <5) showed lower cardiac alterations compared to NASH patients (NAS score >5). After adjusting for age, sex and BMI, a positive correlation was found only between LV mass and NAS score (p < 0.001). CONCLUSION: Our results suggest that cardiac dysfunction can be detectable early in NAFLD children and this is not linked to cardiovascular and metabolic alteration, other than to liver damage. Although as a preliminary stage, we can speculate a possible direct relationship between liver and heart steatosis, already occurring during childhood.

Diagnostic value of p16 methylation for malignant pleural effusion a meta-analysis / Valor diagnóstico de la metilación p16 en el derrame pleural maligno un meta-análisis

OBJECTIVE: To evaluate the overall diagnostic performance of the p16 methylation for diagnosing malignant pleural effusion (MPE). METHODS: All published literature in English and Chinese were reviewed. Sensitivity, specificity, likelihood ratio and diagnostic odds ratio (DOR) were pooled by using random-effects model or fixed-effects model. Summary receiver operating characteristic (SROC) curve was used to evaluate the overall diagnostic value. RESULTS: Six studies were included with a total of 378 cases. The sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR) and DOR of p16 methylation in the diagnosis of MPE were 0.41 [95% confidence interval (CI) 0.35, 0.48], 0.97 [95% CI 0.93, 0.99], 9.57 [95% CI 4.53, 20.20], 0.61 [95% CI 0.45, 0.82] and 19.82 [95% CI 8.35, 47.04], respectively. The area under the curve (AUC) was 0.864. CONCLUSION: Pleural p16 methylation test plays a useful role in the diagnosis of MPE.

OBJETIVO: Evaluar el rendimiento diagnóstico general de la metilación p16 para el diagnóstico del derrame pleural maligno (DPM). MÉTODOS: Se revisó toda la literatura publicada en inglés y chino. La sensibilidad, especificidad, razón de verosimilitud, y el odds-ratio diagnóstico (DOR) fueron agrupados mediante el modelo de efectos aleatorios o el modelo de efectos. La curva de las características operativas de resumen del receptor (SROC) fue usada para evaluar el valor diagnóstico general. RESULTADOS: Se incluyeron seis estudios con un total de 378 casos. La sensibilidad, especificidad, razón de verosimilitud positiva (PLR), razón de verosimilitud negativa (NLR) y el DOR de la metilación p16 en el diagnóstico de DPM, fueron 0.41 [95% intervalo de confianza (IC) 0.35 0.48], 0.97 [95% IC 0.93, 0.99], 9.57 [95% IC 4.53, 20.20], [95% IC 0.45, 0.82] 0.61 y 19.82 [95% IC 8.35, 47.04], respectivamente. El área bajo la curva (AUC) fue 0.864. CONCLUSIÓN: La prueba de metilación p16 pleural desempeña un papel útil en el diagnóstico del DPM.

Partial normalization of components of metabolic syndrome does not influence prevalent echocardiographic abnormalities: the HyperGEN study.

BACKGROUND AND AIMS: Metabolic syndrome (MetS) is a complex condition characterized by different phenotypes, according to the combinations of risk factors and is associated with cardiovascular abnormalities. Whether control of MetS components by treatment produces improvement in the associated cardiovascular abnormalities is unknown. We investigated whether partial control of components of MetS was associated with less echocardiographic abnormalities than the complete presentation of MetS based on measured components. METHODS AND RESULTS: We evaluated markers of echocardiographic preclinical cardiovascular disease in MetS (ATP III) defined by measured components or by history of treatment, in 1421 African-American and 1195 Caucasian non-diabetic HyperGEN participants, without prevalent cardiovascular disease or serum creatinine >2 mg/dL. Of 2616 subjects, 512 subjects had MetS by measured components and 328 by history. Hypertension was found in 16% of participants without MetS, 6% of those with MetS by history and 42% of those with MetS by measured components. Obesity and central fat distribution had similar prevalence in both MetS groups (both p < 0.0001 vs. No-MetS). Blood pressure was similar in MetS by history and No-MetS, and lower than in MetS by measured components (p < 0.0001). LV mass and midwall shortening, left atrial (LA) dimension and LA systolic force were similarly abnormal in both MetS groups (all p < 0.0001 vs. No-MetS) without difference between them. CONCLUSIONS: There is a little impact of control by treatment of single components of MetS (namely hypertension) on echocardiographic abnormalities. Lower blood pressure in participants with MetS by history was not associated with substantially reduced alterations in cardiac geometry and function.

Does cardiovascular phenotype explain the association between diabetes and incident heart failure? The Strong Heart Study.

BACKGROUND AND AIMS: Diabetes remains a predictor of incident heart failure (HF), independent of intercurrent myocardial infarction (MI) and concomitant risk factors. Initial cardiovascular (CV) characteristics, associated with incident heart failure (HF) might explain the association of diabetes with incident HF. METHODS AND RESULTS: Participants to the 2nd Strong Heart Study exam, without prevalent HF or coronary heart disease, or glomerular filtration rate <30 mL/min/1.73 m(2), were analyzed (n = 2757, 1777 women, 1278 diabetic). Cox regression of incident HF (follow-up 8.91 ± 2.76 years) included incident MI censored as a competing risk event. Acute MI occurred in 96 diabetic (7%) and 84 non-diabetic participants (6%, p = ns). HF occurred in 156 diabetic (12%) and in 68 non-diabetic participants (5%; OR = 2.89, p < 0.001). After accounting for competing MI and controlling for age, gender, BMI, systolic blood pressure, smoking habit, plasma cholesterol, antihypertensive treatment, heart rate, fibrinogen and C-reactive protein, incident HF was predicted by greater LV mass index, larger left atrium, lower systolic function, greater left atrial systolic force and urinary albumin/creatinine excretion. Risk of HF was reduced with more rapid LV relaxation and anti-hypertensive therapy. Diabetes increases hazard of HF by 66% (0.02 < p < 0.001). The effect of diabetes could be explained by the level of HbA1c. CONCLUSIONS: Incident HF occurs more frequently in diabetes, independent of intercurrent MI, abnormal LV geometry, subclinical systolic dysfunction and indicators of less rapid LV relaxation, and is influenced by poor metabolic control. Identification of CV phenotype at high-risk for HF in diabetes should be advised.

Effect of canrenone on left ventricular mechanics in patients with mild systolic heart failure and metabolic syndrome: the AREA-in-CHF study.

BACKGROUND AND AIM: We analyzed the effect of the mineralocorticoid receptor antagonist canrenone on LV mechanics in patients with or without metabolic syndrome (MetS) and compensated (Class II NYHA) heart failure (HF) with reduced ejection fraction (EF≤45%) on optimal therapy (including ACE-i or ARB, and ß-blockers). METHODS AND RESULTS: From a randomized, double-blind placebo-controlled trial (AREA-in-CHF), patients with (73 on canrenone [Can] and 77 on placebo [Pla]), based on modified ATPIII definition (BMI≥30kg/m(2) instead of waist girth) or without MetS (146 by arm). In addition to traditional echocardiographic parameters, we also evaluated myocardial mechano-energetic efficiency (MME) based on a previously reported method. At baseline, Can and Pla did not differ in age, BMI, blood pressure (BP), metabolic profile, BNP, and PIIINP. Compared with MetS-Pla, and controlling for age, sex and diabetes, at the final control MetS-Can exhibited increased MME, preserved E/A ratio, and decreased atrial dimensions (0.04

Metabolic syndrome and left ventricular hypertrophy in the prediction of cardiovascular events: the Strong Heart Study.

BACKGROUND AND AIMS: Metabolic syndrome (MetS) is associated with increased prevalence of echocardiographic LV hypertrophy (LVH), a potent predictor of cardiovascular (CV) outcome. Whether MetS increases risk of CV events independently of presence of LVH has never been investigated. It is also unclear whether LVH predicts CV risk both in the presence and absence of MetS. METHODS AND RESULTS: Participants in the 2nd Strong Heart Study examination without prevalent coronary heart disease, congestive heart failure or renal insufficiency (plasma creatinine >2.5mg/dL) were studied (n=2758; 1746 women). MetS was defined by WHO criteria. Echocardiographic LV hypertrophy was defined using population-specific cut-point value for LV mass index (>47.3g/m(2.7)). After controlling for age, sex, LDL-cholesterol, smoking, plasma creatinine, diabetes, hypertension and obesity, participants with MetS had greater probability of LVH than those without MetS (OR=1.55 [1.18-2.04], p<0.002). Adjusted hazard of composite fatal and non-fatal CV events was greater when LVH was present, in participants without (HR=2.03 [1.33-3.08]) or with MetS (HR=1.64 [1.31-2.04], both p<0.0001), with similar adjusted population attributable risk (12% and 14%). After adjustment for LVH, risk of incident CV events remained 1.47-fold greater in MetS (p<0.003), an effect, however, that was not confirmed when diabetic participants were excluded. CONCLUSION: LVH is a strong predictor of composite 8-year fatal and non-fatal CV events either in the presence or in the absence of MetS and accounts for a substantial portion of the high CV risk associated with MetS.