Diagnosing Fabry nephropathy: the challenge of multiple kidney disease.

Fabry disease (FD) is an X-linked inherited lysosomal disorder due to a deficiency of the enzyme alpha-galactosidase A (α-gla) due to mutations in the GLA gene. These mutations result in plasma and lysosome accumulation of glycosphingolipids, leading to progressive organ damage and reduced life expectancy. Due to the availability of specific disease-modifying treatments, proper and timely diagnosis and therapy are essential to prevent irreversible complications. However, diagnosis of FD is often delayed because of the wide clinical heterogeneity of the disease and multiple organ involvement developing in variable temporal sequences. This observation is also valid for renal involvement, which may manifest with non-specific signs, such as proteinuria and chronic kidney disease, which are also common in many other nephropathies. Moreover, an additional confounding factor is the possibility of the coexistence of FD with other kidney disorders. Thus, suspecting and diagnosing FD nephropathy in patients with signs of kidney disease may be challenging for the clinical nephrologist. Herein, also through the presentation of a unique case of co-occurrence of autosomal dominant polycystic kidney disease and FD, we review the available literature on cases of coexistence of FD and other renal diseases and discuss the implications of these conditions. Moreover, we highlight the clinical, laboratory, and histological elements that may suggest clinical suspicion and address a proper diagnosis of Fabry nephropathy.

Beneficial Effects of IABP in Anterior Myocardial Infarction Complicated by Cardiogenic Shock.

Background and Objectives. Recent guidelines have downgraded the routine use of the intra-aortic balloon pump (IABP) in patients with cardiogenic shock (CS) due to ST-elevation myocardial infarction (STEMI). Despite this, its use in clinical practice remains high. The aim of this study was to evaluate the prognostic impact of the IABP in patients with STEMI complicated by CS undergoing primary PCI (pPCI), focusing on patients with anterior MI in whom a major benefit has been previously hypothesized. Materials and Methods. We enrolled 2958 consecutive patients undergoing pPCI for STEMI in our department from 2005 to 2018. Propensity score matching and mortality analysis were performed. Results. CS occurred in 246 patients (8.3%); among these patients, 145 (60%) had anterior AMI. In the propensity-matched analysis, the use of the IABP was associated with a lower 30-day mortality (39.3% vs. 60.9%, p = 0.032) in the subgroup of patients with anterior STEMI. Conversely, in the whole group of CS patients and in the subgroup of patients with non-anterior STEMI, IABP use did not have a significant impact on mortality. Conclusions. The use of the IABP in cases of STEMI complicated by CS was found to improve survival in patients with anterior infarction. Prospective studies are needed before abandoning or markedly limiting the use of the IABP in this clinical setting.

Percutaneous artErial closure devices and ultrasound-guided Trans-femoRal puncture ObservatioNal InvestigatiOn: Insights from the PETRONIO registry.

OBJECTIVE: To evaluate the safety of a single and combined use of ultrasound-guided femoral puncture (U) and percutaneous arterial closure devices (P) in femoral artery procedures (FAP) compared to fluoroscopic guidance (F) and manual compression (M) in a large radial-focused interventional centre. BACKGROUND: U and P, taken individually, have improved safety in femoral arterial access procedures compared to traditional techniques. METHODS: All FAP performed between July 2017 and December 2018 in our centre were divided into three phases: (a) control period with F and M mainly performed; (b) phase out period where U and P were introduced; (c) intervention period where a 6-month expertise on the novel techniques was acquired. The overall population was further stratified into subgroups: F/M, U/M, F/P, U/P. The primary study endpoint was in-hospital access site bleeding events (BE) according to the BARC criteria. The secondary endpoint was vascular site complications (VASC). RESULTS: Four hundred eighteen procedures (14%) out of 3025 were performed via FA access during the study period. The overall access-site in-hospital BE were 97 (23%). Decreasing rates of BE (phase 1: n = 46, 29%; phase 2: n = 38, 22% e phase 3: n = 13, 15%; p = 0.027) and VASC were observed during the three periods. BE occurred significantly more often in F/M group (F/M: n = 48; 32%; U/M: n = 12, 16%; F/P: n = 18, 21%; U/P: n = 19, 17%; p = 0.008). F/M subgroup was an independent predictor of BE both in multivariable analysis and propensity score matching analysis. CONCLUSIONS: The introduction of ultrasound-guided femoral puncture and percutaneous arterial closure devices has reduced access site bleedings with a progressive improvement after the first 6 months learning period.

Serum uric acid in patients with ST-segment elevation myocardial infarction: An innocent bystander or leading actor?

Elevated serum uric acid (SUA) levels have been associated with several cardiovascular risk factors and the progression of coronary artery disease. In the setting of acute myocardial infarction, increasing evidence suggests that high SUA levels could be related to adverse outcomes. Interestingly elevated SUA levels have been linked to endothelial dysfunction, inflammation and oxidative stress. The aim of this review is to discuss the potential negative effects of SUA in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention, analyzing the possible underlying pathophysiological mechanisms.

A reliable fossa ovalis impedance mapping for safer transseptal puncture: A new vision beyond voltage.

INTRODUCTION: Transseptal puncture (TSP) is widely used in clinical practice but is negatively affected by a nonneglectable rate of complications and X-ray exposure. To address these problems, we investigated whether or not impedance mapping could correctly identify fossa ovalis (FO) and safely guide TSP. METHODS AND RESULTS: Electroanatomic mapping was performed with CARTO 3 system version 7 and a ThermoCool® SmartTouch® mapping catheter was employed. In each patient, an impedance map and a bipolar voltage map of the whole interatrial septum were collected, acquiring at least 150 points with a contact force ≥2 g and using the pattern matching filter. Thirty-five patients were enrolled. A low impedance area was clearly identified in 34 of them. In 30 patients (88%), the FO was located in the low impedance area. The map was obtained in sinus rhythm in 17 cases (50%); in 15 of these (88%), the TSP site, the patent foramen ovale, or the FO tenting area fell inside the low impedance area. The same numbers were observed when mapping during atrial fibrillation. CONCLUSION: To the best of our knowledge, this is the first study that provides the reliability and reproducibility of impedance mapping in identifying FO, an affordable and feasible tool that could be potentially introduced into clinical practice.

Extracorporeal veno-venous ultrafiltration in patients with acute heart failure.

Hospitalization for congestive heart failure represents a growing burden for health care systems. Heart failure is characterized by extracellular fluid overload and loop diuretics have been for decades the cornerstone of therapy in these patients. However, extensive use of intra-venous diuretics is characterised by several limitations: risk of worsening renal function and electrolyte imbalance, symptomatic hypotension and development of diuretic resistance. Extracorporealveno-venous ultrafiltration (UF) represents an interesting adjunctive therapy to target congestion in patients with heart failure and fluid overload. UF consists of the mechanical removal of iso-tonic plasma water from the blood through a semipermeable membrane using a pressure gradient generated by a pump. Fluid removal through UF presents several advantages such as removal of higher amount of sodium, predictable effect, limited neuro-hormonal activation, and enhanced spontaneous diuresis and diuretic response. After twenty years of "early" studies, since 2000 some pilot studies and randomized clinical trials with modern devices have been carried out with somehow conflicting results, as discussed in this review. In addition, some practical aspects of UF are addressed.

Transcatheter mitral valve repair with MitraClip in patients with pulmonary hypertension: hemodynamic and prognostic perspectives.

Transcatheter mitral valve repair with MitraClip has emerged as a possible therapeutic option for patients with severe mitral regurgitation (MR) with high risk for surgical valve repair. MitraClip intervention has demonstrated to improve haemodynamics and clinical outcomes in selected patients in observational and randomized studies. Preoperative pulmonary hypertension (PH) is known to affect prognosis in patients undergoing surgical mitral valve intervention. The aim of the present review is to discuss the available literature focused on the haemodynamic and clinical effects of MitraClip in patients with severe MR and PH.

A preprocedural risk score predicts acute kidney injury following primary percutaneous coronary intervention.

BACKGROUND: Reliable preprocedural risk scores for the prediction of Contrast-Induced Acute Kidney Injury (CI-AKI) following Percutaneous Coronary Intervention (pPCI) in patients with ST-elevation myocardial infarction (STEMI) are lacking. Aim of this study was to derive and validate a preprocedural Risk Score in this setting. METHODS: Two prospectively enrolled patient cohorts were used for derivation and validation (n = 3,736). CI-AKI was defined as creatinine increase ≥0.5 mg/dl <72 h postpPCI. Odds ratios from multivariable logistic regression model were converted to an integer, whose sum represented the Risk Score. RESULTS: Independent CI-AKI predictors were: diabetes, Killip class II-III (2 points each), age > 75 years, anterior MI (3 points), Killip class IV (4 points), estimated GFR < 60 ml/min/1.73m2 (5 points). The Risk Score c-statistic was 0.84 in both cohorts. Compared with patients with Risk Score ≤ 4, the relative risks of CI-AKI among patients scoring 5-9 were 6.2 (derivation cohort) and 7.1 (validation cohort); among patients scoring ≥10, 19.8, and 21.4, respectively. CONCLUSIONS: Among STEMI patients, a simple preprocedural Risk Score accurately and reproducibly predicted the risk of CI-AKI, identifying » of patients with a seven-fold risk and 1/10 of patients with a 20-fold risk. This knowledge may help tailored strategies, including delaying revascularization of nonculprit vessels in patients at high risk of CI-AKI.

Elevated serum uric acid is associated with a greater inflammatory response and with short- and long-term mortality in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention.

BACKGROUND AND AIMS: Despite elevated serum uric acid (eSUA) has been identified as independent risk factor for cardiovascular diseases, its prognostic value in the setting of ST-segment elevation myocardial infarction (STEMI) is still controversial. Although the mechanisms of this possible relationship are unsettled it has been suggested that eSUA could trigger the inflammatory response. This study sought to investigate the association between eSUA with short- and long-term mortality and with inflammatory response in patients with STEMI treated with primary percutaneous coronary intervention (pPCI). METHODS AND RESULTS: Blood samples were collected on admission and at 24 and 48 h after pPCI: the inflammatory biomarkers C-reactive protein (CRP), neutrophil count and neutrophil to lymphocytes ratio (NLR) were considered. Baseline eSUA was defined as ≥6.8 mg/dl. Cumulative 30-days and 1-year mortalities were estimated using the Kaplan-Meyer analysis. Multivariable analyses were performed by Cox proportional hazard models. In the 2369 patients with STEMI considered, 30-day mortality was 5.8% among patients with eSUA and 2% among patient with normal SUA level (p < 0.001); 1-year mortality was 8.5% vs 4%, respectively (p < 0.001). At multivariable analyses eSUA was an independent predictor of 30-day mortality (HR 1.196, 95%CI 1.006-1.321, p = 0.042) and 1-year mortality (HR 1.178, 95%CI 1.052-1.320, p = 0.005). eSUA patients presented higher values in on admission CRP (p < 0.001) and in neutrophil count and NLR at 24 h (respectively, p = 0.020 and p < 0.001) and at 48 h (p = 0.018 and p < 0.001) compared to patients with normal SUA levels. CONCLUSIONS: Elevated serum uric acid is associated with higher short- and long-term mortality and with a greater inflammatory response after reperfusion in patients with STEMI treated with primary PCI.

Elevated serum uric acid is a predictor of contrast associated acute kidney injury in patient with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention.

BACKGROUND: Contrast associated-acute kidney injury (CA-AKI) has been associated with adverse outcomes after ST-segment elevation myocardial infarction (STEMI). However, early markers of CA-AKI are still needed to improve risk stratification. We investigated the association between elevated serum uric acid (eSUA) and CA-AKI in patients with STEMI treated with primary percutaneous coronary intervention (pPCI). METHODS AND RESULTS: Serum creatinine (Scr) was measured at admission and 24, 48 and 72 h after pPCI. CA-AKI was defined as an increase of 25% (CA-AKI 25%) or 0.5 mg/dl (CA-AKI 0.5) of Scr level above the baseline after 48 h following contrast administration. Multivariable analyses to investigate CA-AKI predictors were performed by binary logistic regression and multivariable backward logistic regression model. In the 3023 patients considered, CA-AKI was more frequent among patients with eSUA as compared with patients with normal SUA levels, considering both CA-AKI definitions (CA-AKI25%: 20.8% vs 16.2%, p < 0.012; CA-AKI 0.5: 10.1% vs 5.8%, p < 0.001). The association between eSUA and CA-AKI was confirmed at multivariable analyses (CA-AKI 25%: odd ratio 1.32, 95% CI 1.03-1.69, p = 0.027; CA-AKI 0.5: odd ratio 1.76, 95% CI 1.11-2.79, p = 0.016). CONCLUSION: Elevated serum uric acid is associated with CA-AKI after reperfusion in patients with STEMI treated with pPCI.

Has hyperglycemia a different prognostic role in STEMI patients with or without diabetes?

BACKGROUND AND AIMS: Hyperglycemia at hospital admission is a common finding in patients with STEMI. However, whether elevated acute glycemia in these patients may have a direct impact on worsening prognosis or is just a marker of a greater neurohormonal activation in response to the infarction is still unsettled. We sought to investigate the prognostic impact of hyperglycemia at hospital admission in patients undergoing primary PCI (pPCI) for STEMI, and the influence of the presence of diabetes mellitus (DM) on its prognostic impact. METHODS: and Results, We enrolled 2958 consecutive STEMI patients treated by pPCI. Hyperglycemia was defined as plasma glucose >198 mg/dL (or >11 mmol/L). Patients with hyperglycemia showed a greater risk-profile; they also experienced a higher mortality both at univariable (17.6% vs 5.2%, p < 0.001) and multivariable (HR 1.9, 95%IC 1.5-2.9, p = 0.001) analysis. However, after stratification for DM presence, hyperglycemia resulted as an independent predictor of mortality only in patients without DM (HR 2, 95%IC 1.2-3.4, p = 0.01). CONCLUSION: Hyperglycemia in the setting of myocardial infarction treated with primary PCI in an independent predictor of all-cause mortality in patients without diabetes; in patients with diabetes, its prognostic impact seems attenuated.

ANMCO POSITION PAPER: Role of intra-aortic balloon pump in patients with acute advanced heart failure and cardiogenic shock.

The treatment of patients with advanced acute heart failure is still challenging. Intra-aortic balloon pump (IABP) has widely been used in the management of patients with cardiogenic shock. However, according to international guidelines, its routinary use in patients with cardiogenic shock is not recommended. This recommendation is derived from the results of the IABP-SHOCK II trial, which demonstrated that IABP does not reduce all-cause mortality in patients with acute myocardial infarction and cardiogenic shock. The present position paper, released by the Italian Association of Hospital Cardiologists, reviews the available data derived from clinical studies. It also provides practical recommendations for the optimal use of IABP in the treatment of cardiogenic shock and advanced acute heart failure.

Leptin affects the inflammatory response after STEMI.

Leptin is an adipose tissue-derived hormone primarily involved in the regulation of food intake. Leptine has been shown to have a much broader role than just regulating body weight and appetite in response to food intake: among the others, it has been associated with increased ROS production and inflammation, factors involved in the restoration of an effective myocardial reperfusion after myocardial revascularization. Our study, to our best knowledge, is the first showing a direct relationship between leptin serum levels, inflammatory mediators of the ischemia reperfusion damage and effective myocardial reperfusion in patients with ST elevation myocardial infarction undergoing primary percutaneous coronary intervention. Our findings suggest that leptin serum levels are directly associated with the inflammatory response during an acute myocardial infarction and may have a role in risk stratification in this clinical setting.

Favorable effect of glycoprotein IIbIIIa inhibitors among STEMI patients treated with primary PCI and incomplete ST resolution.

Incomplete ST resolution after primary percutaneous coronary interventions (pPCI) in STEMI patients is a well known prognostic marker, associated with the occurrence of microvascular obstruction and increased mortality. The effects of the use of glycoprotein IIbIIIa inhibitors (GPIs) in this peculiar subset of high- risk patients is still unknown. The aim of the present study was to assess whether the GPIs administration would result in improved outcome in ST elevation myocardial infarction (STEMI) patients with incomplete ST resolution (ISTR).All consecutive STEMI patients who underwent pPCI at our hospital between 2005 and 2014 were enrolled (n = 2001). ST resolution was defined as incomplete with a < 70% resolution of initial ST shift. Mortality analyses were performed by Kaplan-Meier curves, multivariable analysis through Cox regressions and propensity matching score. The incidence of ISTR was 29% (n = 592). Among ISTR patients, GPIs use was an independent predictor of better prognosis (HR 0.39, 95% CI 0.16-0.96, p < 0.04). Propensity matched analysis confirmed that the use of GPIs was associated with a lower 30-day (6.1% vs 13.4%, p = 0.02) and 1-year (8.4% vs 15.1%, p = 0.045) mortality. STEMI patients treated with pPCI and presenting ISTR show a poor outcome. The use of GPIs in these patients is associated with improved survival at 30 days and at 1 year; the causes for these favorable effects remain speculative and could be related to the development and evolution of microvascular obstruction.

Cigarette smoking reduces platelet reactivity independently of clopidogrel treatment in patients with non-ST elevation acute coronary syndromes.

Smokers receiving clopidogrel show a lower residual platelet reactivity than non-smokers, a phenomenon generally ascribed to smoking-induced increased production of clopidogrel active metabolite, but also associated with the high hemoglobin levels of smokers, which decreases platelet reactivity in tests that measure platelet function in whole blood. We evaluated the impact of cigarette smoking and of hemoglobin levels on platelet reactivity index (PRI) measured by the vasodilator-stimulated phosphoprotein phosphorylation (VASP-P) assay in whole blood samples from patients with non-ST elevation acute coronary syndrome (NSTE-ACS) undergoing percutaneous coronary interventions, both before and after clopidogrel administration. PRI was measured in 718 clopidogrel-naïve NSTE-ACS patients, both before and 1 month after treatment with clopidogrel (75 mg daily). Smokers (n = 347, 48%) had significantly lower mean PRI levels at both baseline (57.7 ± 24.1 vs. 64.8 ± 19.8, p < 0.001) and 1 month (43.4 ± 20.3% vs. 46.8 ± 18.0%, p = 0.017) than non-smokers. After adjusting for potential confounders (age, sex, diabetes, chronic kidney disease, Syntax score>15), the ß coefficient of smoke on PRI was -8.51 [-11.90 to -5.11, p < 0.001] at baseline and -3.41 [-6.30 to -0.51, p = 0.02] after 1 month. Hemoglobin was higher in smokers (13.8 ± 1.5 g/dL) than non-smokers (13.1 ± 1.7 g/dL, p < 0.001), but was not significantly correlated with PRI both at baseline (Rho = 0.02, p = 0.60) and at 1 month (Rho = 0.01, p = 0.80). Our analysis confirms that clopidogrel-treated smokers have lower platelet reactivity, measured by the VASP-P assay, compared to clopidogrel-treated non-smokers. However, smokers had lower platelet reactivity already before receiving clopidogrel treatment, suggesting that smoke affects platelet reactivity independently of its potential effect on the pharmacokinetics of clopidogrel. Our data also indicate that such an effect is not mediated by increased hemoglobin levels.

Systemic inflammatory status is associated with increased platelet reactivity in the early period after acute coronary syndromes.

Systemic inflammation measured by high-sensitivity C reactive protein (CPR) is associated with increased risk of major adverse cardiovascular events (MACE). Recent clinical trials targeting CPR showed a reduction in MACE after an acute coronary syndrome (ACS). Inflammation could be linked to high platelet reactivity (HPR), which is an independent predictor of MACE in patients with ACS. We aimed to evaluate the impact of 1-month C-reactive Protein (CRP) levels on HPR in patients enrolled in the GEPRESS study. We measured CRP and platelet reactivity index (PRI) at 30 days follow-up. PRI was assessed with vasodilator stimulated phosphoprotein (VASP) phosphorylation assay at the same timepoint. HPR was defined as PRI >50%. Of the 1042 patients included in the GEPRESS study, 756 (75%) had both VASP and CRP data at 30 days follow-up. HPR was found in 61 (49.1%) patients with CRP >1 mg/L and 233 (36.4%) patients with CRP ≤1 mg/L, p = 0.012. After adjustment for covariates, we found a direct gradient of effect between CRP and HPR; the inclusion of CRP significantly increased the discrimination of HPR regression model. This is the first study showing that residual HPR is more likely to occur in patients with CRP >1 mg/L at 1 month after non-ST elevation-ACS and this may contribute to the unfavorable outcome observed in such patients.

Complete chest recoil during laypersons' CPR: Is it a matter of weight?

INTRODUCTION: Chest compressions depth and complete chest recoil are both important for high-quality Cardio-Pulmonary Resuscitation (CPR). It has been demonstrated that anthropometric variables affect chest compression depth, but there are no data about they could influence chest recoil. The aim of this study was to verify whether physical attributes influences chest recoil in lay rescuers. METHODS: We evaluated 1 minute of compression-only CPR performed by 333 laypersons immediately after a Basic Life Support and Automated External Defibrillation (BLS/AED) course. The primary endpoint was to verify whether anthropometric variables influence the achievement a complete chest recoil. Secondary endpoint was to verify the influence of anthropometric variables on chest compression depth. RESULTS: We found a statistically significant association between weight and percentage of compressions with correct release (p≤0.001) and this association was found also for height, BMI and sex. People who are heavier, who are taller, who have a greater BMI and who are male are less likely to achieve a complete chest recoil. Regarding chest compressions depth, we confirm that the more a person weighs, the more likely the correct depth of chest compressions will be reached. CONCLUSIONS: Anthropometric variables affect not only chest compression depth, but also complete chest recoil. CPR instructors should tailor their attention during training on different aspect of chest compression depending on the physical characteristics of the attendee.

Fat-to-lean mass ratio as a tool to detect the dysmetabolic profile in childhood cancer survivors.

INTRODUCTION: Survival after childhood cancer has significantly improved in recent decades. Nevertheless, an increased incidence of metabolic syndrome and cardiovascular disease among childhood cancer survivors (CCS) has been reported. The aim of this study was to evaluate whether fat-to-lean mass ratio (FLR) is associated with a dysmetabolic profile in CCS. METHODS: At least 2 years from completion of therapy, data from CCS aged 10 to 16 years at follow-up and without any concurrent steroid treatment were collected. Body mass index, waist circumference (WC), WC-to-height ratio, laboratory blood tests, and FLR calculated by dual-energy X-ray absorptiometry measurements were considered. Body mass index >85th percentile and >97th percentile, WC >90th percentile, and WC-to-height ratio > 0.5 were chosen as criteria of overweight and obesity, visceral obesity, and increased cardiovascular risk, respectively. RESULTS: We enrolled 205 CCS previously treated for hematologic cancer or solid or central nervous system tumor. The best cutoff of FLR was 0.6. CCS; those with FLR ≥0.6 (43%) were more frequently overweight and obese (P < 0.001), and presented with higher levels of triglycerides (P = 0.011), homeostatic model assessment for insulin resistance (P = 0.001), alanine transaminase (P = 0.004), and trunk fat (P < 0.001) and lower levels of insulin-like growth factor 1 (P < 0.001) and lean mass (P = 0.009). WC >90th percentile (P = 0.007), insulin-like growth factor 1 (P = 0.002), and trunk fat (P = 0.006) were independent predictors of FLR ≥0.6 in a model including all the previous variables. CONCLUSIONS: An increased FLR is suggestive of altered body composition phenotype, allowing identification of CCS at higher risk of metabolic syndrome. Diet and physical activity are needed from commencement of oncological treatments to preserve overall nutritional status and maintain it over the long term.