Heart failure with preserved ejection fraction in elderly. From pathophysiology to treatment: an unresolved problem.

Heart failure with preserved ejection fraction (HFpEF) has a significant impact on healthcare resources and while its occurrence in the elderly is increasing, its prognosis has not improved. Despite the prevalence of HFpEF, the understanding of its pathophysiology is still incomplete, and optimal treatment remains largely undefined. The net clinical benefit of medical treatment with ACE inhibitors, ARBs, MRAs and beta-blockers has led to the incorporation of these drugs into HF clinical practice guidelines. However, little or no progress has been done for patients with HFpEF and there are no convincing and validated therapies able to reduce mortality or morbidity. HFpEF is a heterogeneous clinical syndrome embracing varieties of phenotypes and could benefit from a phenotype-specific approach. In the era of precision medicine, targeted approaches have proved effective in various disciplinary medical settings and for this reason this modern approach should be encouraged also in cardiology. In elderly patients, multi-level strategies and interventions aimed at improving adherence to guidelines and tailoring therapy, could be the key to improving outcome, and to reducing costs related to HF-related re-admissions. In the present review we briefly discuss current information available regarding pathophysiology, outcome, treatment and safety of the most common drugs used in this "geriatric syndrome"

Resin infiltrant for non-cavitated caries lesions: evaluation of color stability

The objective of this in vitro study was to evaluate the over time color stability of one resin infiltrant (Icon) upon exposure to staining solutions (coffee and wine) compared with one nano-hybrid sealant (Grandio Seal), one transparent fissure sealant with fluoride (Control Seal) and one nanofilled composite (Filtek Supreme XTE). All materials were polymerized according to manufacturers’ instructions into silicon rings (height 1 mm; internal diameter 6 mm; external diameter 8 mm) to obtain specimens identical in size. The specimens were immersed in staining solutions at room temperature over a 28-day test period. The control samples have not been subjected to the staining process. A colorimetric evaluation according to the CIE L*a*b* system was performed by a blind trained operator at 7, 14, 21, 28 days of the staining process. Shapiro Wilk test and Kruskal Wallis ANOVA were applied to assess significant differences among different materials. Means were compared with Scheffe’s multiple-comparison test at the 0.05 level of significance. In the case of all materials, immersion in solutions resulted in clinically perceivable color changes after 1 week (∆E 0.05). Color coordinate CIE b* varied similarly for all materials tested (P > 0.05). Immersion in coffee or red wine resulted in clinically perceivable color changes for all materials tested. Icon showed the highest color variations both after 1 week and 1 month. Icon can fix the initial esthetic problem associated with white spot lesions, but the resin may become more discolored than other materials over time

Myocarditis and Chronic Inflammatory Cardiomyopathy, from Acute Inflammation to Chronic Inflammatory Damage: An Update on Pathophysiology and Diagnosis

Acute myocarditis covers a wide spectrum of clinical presentations, from uncomplicated myocarditis to severe forms complicated by hemodynamic instability and ventricular arrhythmias; however, all these forms are characterized by acute myocardial inflammation. The term "chronic inflammatory cardiomyopathy" describes a persistent/chronic inflammatory condition with a clinical phenotype of dilated and/or hypokinetic cardiomyopathy associated with symptoms of heart failure and increased risk for arrhythmias. A continuum can be identified between these two conditions. The importance of early diagnosis has grown markedly in the contemporary era with various diagnostic tools available. While cardiac magnetic resonance (CMR) is valid for diagnosis and follow-up, endomyocardial biopsy (EMB) should be considered as a first-line diagnostic modality in all unexplained acute cardiomyopathies complicated by hemodynamic instability and ventricular arrhythmias, considering the local expertise. Genetic counseling should be recommended in those cases where a genotype-phenotype association is suspected, as this has significant implications for patients' and their family members' prognoses. Recognition of the pathophysiological pathway and clinical "red flags" and an early diagnosis may help us understand mechanisms of progression, tailor long-term preventive and therapeutic strategies for this complex disease, and ultimately improve clinical outcomes

Combined use of lung ultrasound, B-type natriuretic peptide, and echocardiography for outcome prediction in patients with acute HFrEF and HFpEF

Background: Lung ultrasound (LUS) can be used to assess pulmonary congestion by imaging B-lines (‘comets’) for patients with acute heart failure (AHF). Objectives: Investigate relationship of B-lines, plasma concentrations of B-type natriuretic peptide (BNP), and echocardiographic left ventricular (LV) function measured at admission and discharge and their relationship to prognosis for AHF with preserved (HFpEF) or reduced (HFrEF) LV ejection fraction. Methods: Patients with AHF had the above tests done at admission and discharge. The primary outcome was re-hospitalization for heart failure or death at 6 months. Results: Of 162 patients enrolled, 95 had HFrEF and 67 had HFpEF, median age was 80 [77–85] years, and 85 (52%) were women. The number of B-lines at admission (median 31 [27–36]) correlated with respiratory rate (r = 0.75; p < 0.001), BNP (r = 0.43; p < 0.001), clinical congestion score (r = 0.25; p = 0.001), and systolic pulmonary artery pressure (r = 0.42; p < 0.001). At discharge, B-lines were also correlated with BNP (r = 0.69; p < 0.001) and congestion score (r = 0.57; p < 0.001). B-line count at discharge predicted outcome (AUC 0.83 [0.77–0.90]; univariate HR 1.12 [1.09–1.16]; p < 0.001; multivariable HR 1.16 [1.11–1.21]; p < 0.001). Results were similar for HFpEF and HFrEF. Conclusions: LUS appears a useful method to assess severity and monitor the resolution of lung congestion. At hospital admission, B-lines are strongly related to respiratory rate, which may be a key component of the sensation of dyspnea. Measurement of lung congestion at discharge provides prognostic information for patients with either HFpEF or HFrEF

The Different Pathways of Epicardial Adipose Tissue across the Heart Failure Phenotypes: From Pathophysiology to Therapeutic Target

Epicardial adipose tissue (EAT) is an endocrine and paracrine organ constituted by a layer of adipose tissue directly located between the myocardium and visceral pericardium. Under physiological conditions, EAT exerts protective effects of brown-like fat characteristics, metabolizing excess fatty acids, and secreting anti-inflammatory and anti-fibrotic cytokines. In certain pathological conditions, EAT acquires a proatherogenic transcriptional profile resulting in increased synthesis of biologically active adipocytokines with proinflammatory properties, promoting oxidative stress, and finally causing endothelial damage. The role of EAT in heart failure (HF) has been mainly limited to HF with preserved ejection fraction (HFpEF) and related to the HFpEF obese phenotype. In HFpEF, EAT seems to acquire a proinflammatory profile and higher EAT values have been related to worse outcomes. Less data are available about the role of EAT in HF with reduced ejection fraction (HFrEF). Conversely, in HFrEF, EAT seems to play a nutritive role and lower values may correspond to the expression of a catabolic, adverse phenotype. As of now, there is evidence that the beneficial systemic cardiovascular effects of sodium-glucose cotransporter-2 receptors-inhibitors (SGLT2-i) might be partially mediated by inducing favorable modifications on EAT. As such, EAT may represent a promising target organ for the development of new drugs to improve cardiovascular prognosis. Thus, an approach based on detailed phenotyping of cardiac structural alterations and distinctive biomolecular pathways may change the current scenario, leading towards a precision medicine model with specific therapeutic targets considering different individual profiles. The aim of this review is to summarize the current knowledge about the biomolecular pathway of EAT in HF across the whole spectrum of ejection fraction, and to describe the potential of EAT as a therapeutic target in HF

In vitro antibacterial activity of different pulp capping materials

Background: Direct pulp capping involves the application of a dental material to seal communications between the exposed pulp and the oral cavity (mechanical and carious pulp exposures) in an attempt to act as a barrier, protect the dental pulp complex and preserve its vitality. The aim of this study was to evaluate and compare, by the agar disc diffusion test, the antimicrobial activity of six different pulp-capping materials: Dycal (Dentsply), Calcicur (Voco), Calcimol LC (Voco), TheraCal LC (Bisco), MTA Angelus (Angelus), Biodentine (Septodont). Material and Methods: Streptococcus salivarius , Streptococcus sanguis and Streptococcus mutans strains were selected to evaluate the antimicrobial activity by the agar disc diffusion test of different pulp capping materials. Paper disks were impregnated whit each pulp capping materials and placed onto culture agar-plates pre-adsorbed with bacterial cells and further incubated for 24 h at 37°C. The growth inhibition zones around each pulp capping materials were recorded and compared for each bacterial strain. Results: For the investigation of the antibacterial properties the ANOVA showed the presence of significant differences among the various materials. Tukey test showed that MTA-based materials induced lower growth inhibition zones. Conclusions: MTA-based products show a discrete antibacterial activity varying from calcium hydroxide-based materials which present an higher antibacterial activity

Fluoride release and uptake abilities of different fissure sealants

Background: The long-term capability of resin sealants and glass ionomer cements to release fluoride is associated to a reduction in pit and fissure caries. The regular use of fluoride varnishes/toothpastes can result in the absorption of fluoride into the sealant. The objective of the present study was to assess the fluoride release/uptake capacities of different fissure sealants. Material and Methods: Three different fissure sealants (Fuji Triage/GC, Fissurit FX/Voco and Grandio Seal/Voco) were examined. Ten discs of each material were prepared. Each disc was incubated with distilled water and then the solution analyzed for diluted for fluoride concentration, using a combination of fluoride electrode (OrionGP 1 S/N 13824, Orion Research Inc, Boston, MA, USA) connected to an expandable ion analyzer (Orion 720A, Orion Research Inc, Boston, MA, USA). Standard curves between 1 and 100 ppm F- were used to calibrate the electrode. Cumulative fluoride release was measured on days 1, 2, 3, 5, 7, 21, 35 and 49, then two different fluoride varnishes/ pastes (Profluorid Varnish/Voco, MI Paste Plus/GC), were applied to the sealants tested, and fluoride release (after reuptake) was measured on days 56, 70 and 84. Results: Kruskal Wallis test confirmed significant differences in fluoride release between Fuji Triage/GC and Fissurit FX/Voco and Grandio Seal/Voco from day 1 ( P < 0.001). The application of fluoride varnish Profluorid Varnish enhanced the fluoride release for all sealants ( P < 0.05). MI Paste Plus enhanced the fluoride release for all sealants except for Fuji Triage/GC ( P > 0.05). Conclusions: The GIC-based sealant (Fuji Triage/GC) released significantly more fluoride than the resin sealants tested. The exposure to the fluoridated varnish (Profluorid Varnish) significantly recharged the sealants tested more than the CPP-ACPF toothpaste (MI Paste Plus)

Effect of glycine pretreatment on the shear bond strength of a CAD/CAM resin nano ceramic material to dentin

Background: The purpose of this study was to evaluate the effect of glycine pretreatment on the shear bond strength between dentin and a CAD/CAM resin nano ceramic material (LavaTM Ultimate Restorative), bonded together with adhesive cements using three different luting protocols (total-etch; self-etch; self-adhesive). Material and Methods: Thirty cylinders were milled from resin nano ceramic blocks with CAD/CAM technology. The cylinders were subsequently cemented to the exposed dentin of 30 bovine permanent mandibular incisors. The specimens were assigned into six groups of five teeth each according to luting procedure and dentin pretreatment. In the first two groups (A1, A2) 10 cylinders were cemented using a total-etch protocol; in groups B1 and B2, 10 cylinders were cemented using a self-etch protocol; in groups C1 and C2, 10 cylinders were cemented using a self-adhesive protocol; in groups A1, B1 and C1 the dentinal surface was also treated with glycine powder. All cemented specimens were submitted to a shear bond strength test. Statistical analysis was performed with Stata 9.0 software. Results: ANOVA showed the presence of significant differences among the various groups ( P <0.0001). Conclusions: Glycine did not change the different bond strength demonstrated by the various luting protocols tested. Conventional resin composite cements used together with a self-etch adhesive reported the highest values. However the use of glycine seems to increase the bond strength of self-adhesive resin cements

Color stability of CAD/CAM Zirconia ceramics following exposure to acidic and staining drinks

The aim of this in vitro study was to evaluate the color stability of CAD/CAM Zirconia ceramics following exposure to acidic drink (Coca Cola) and after exposure to staining solution (coffee). All the samples were immersed in different staining solutions over a 28-day test period. A colorimetric evaluation according to the CIE L*a*b* system was performed by a blind trained operator at 7, 14, 21, 28 days of the staining process. Shapiro Wilk test and Kruskal-Wallis ANOVA were applied to assess significant differences among restorative materials. Paired t-test was applied to test which CIE L*a*b* parameters significantly changed after immersion in staining solutions. One week immersion in acidic drink did not cause a perceivable discoloration for all restorative materials (?E < 3.3). Subsequent immersion in coffee affected color stability of all Zirconia samples, even if Kruskal-Wallis ANOVA found significant differences among the various restorative materials. The ?Es of CAD/CAM Zirconia ceramics after immersion in coffee varied among the products, but color integrity is not affected by contact with acidic drinks