A Comprehensive Assessment of Cardiomyopathies through Cardiovascular Magnetic Resonance: Focus on the Pediatric Population.

Cardiomyopathies (CMPs) are a heterogeneous group of diseases that involve the myocardium and result in systolic or diastolic impairment of the cardiac muscle, potentially leading to heart failure, malignant arrhythmias, or sudden cardiac death. Occurrence in pediatric age is rare but has been associated with worse outcomes. Non-invasive cardiac imaging techniques, integrated with clinical, genetic, and electrocardiographic data, have shown a pivotal role in the clinical work-up of such diseases by defining structural alterations and assessing potential complications. Above all modalities, cardiovascular magnetic resonance (CMR) has emerged as a powerful tool complementary to echocardiography to confirm diagnosis, provide prognostic information and guide therapeutic strategies secondary to its high spatial and temporal resolution, lack of ionizing radiation, and good reproducibility. Moreover, CMR can provide in vivo tissue characterization of the myocardial tissue aiding the identification of structural pathologic changes such as replacement or diffuse fibrosis, which are predictors of worse outcomes. Large prospective randomized studies are needed for further validation of CMR in the context of childhood CMPs. This review aims to highlight the role of advanced imaging with CMR in CMPs with particular reference to the dilated, hypertrophic and non-compacted phenotypes, which are more commonly seen in children.

Factors influencing adults' immunization practices: a pilot survey study of a diverse, urban community in central Ohio.

BACKGROUND: Adult vaccination rates in the United States are well below recommendations with disparities in race, ethnicity, and education level resulting in even lower rates for these populations. This study aimed to identify the barriers to and perceptions of immunizations in adults in an urban, underserved, multicultural community. Understanding the factors that influence adults' decisions to receive routinely recommended vaccines will aid health care providers and public health officials to design programs to improve vaccination rates. METHODS: This cross-sectional, survey-based study was conducted in January 2014 in Columbus, Ohio. Participants were recruited from four urban federally-qualified health centers and four grocery stores affiliated with those clinics. The survey gathered self-reported receipt of immunizations, knowledge about indications for immunizations, and factors influencing decisions to receive an immunization. Data was analyzed in 2014. Descriptive statistics were generated for all survey items and Chi-Square or Fisher's Exact tests were used as appropriate to test for associations between demographic characteristics and factors influencing immunization decisions. RESULTS: The top five factors likely to affect the decision to receive an immunization among the 304 respondents were: "doctor's recommendation" (80.6 %), "knowing why I should get a vaccine" (78.2 %), "knowing which vaccines I need" (75.5 %), cost (54.2 %), and "concern about getting sick if I get a vaccine" (54.0 %). Significant differences in factors influencing the immunization decision exist among respondents based on ethnicity and education level. For those participants with self-identified diabetes, heart disease, or asthma, less than half were aware that certain immunizations could reduce the risk of complications associated with their disease(s). CONCLUSIONS: Data from this study may inform and shape patient education programs conducted in clinics, retailers, and communities, as well as advocacy efforts for adult immunizations. Results from this study suggest that patients would respond to programs for promoting vaccine uptake if they focused on benefits and indications for vaccines. The results also highlighted the need for education regarding immunizations for patients with chronic diseases and special indications. The differences in perceptions found between groups can be used to create targeted interventions based on the needs of those patient populations.

Severe pegfilgrastim-induced bone pain completely alleviated with loratadine: A case report.

Febrile neutropenia is an oncologic emergency that can result in serious consequences. Granulocyte colony stimulating factors (G-CSFs) are often used as prophylaxis for febrile neutropenia. Bone pain is the most notorious adverse effect caused by G-CSFs. Specifically, with pegfilgrastim (Neulasta(®)), the incidence of bone pain is higher in practice than was observed during clinical trials. Traditional analgesics, such as non-steroidal anti-inflammatory drugs (NSAIDs) and opioids, can be ineffective in severe pegfilgrastim-induced bone pain. With the high frequency of this adverse effect, it is clear that health practitioners need additional treatment options for patients who experience severe pegfilgrastim-induced bone pain. The mechanisms of bone pain secondary to G-CSFs are not fully known, but research has shown that histamine release is involved in the inflammatory process. There is scant previous clinical data on antihistamine use in the management of G-CSF-induced pain. We present the first case report in which loratadine prophylaxis completely alleviated NSAID-resistant severe pain secondary to pegfilgrastim. The result showed that loratadine may be a promising option for severe, resistant pegfilgrastim-induced bone pain. Further clinical studies are warranted and ongoing.

Changed outcomes of fetuses with congenital heart disease: new Italian Multicentre study.

OBJECTIVES: To analyse the outcomes of fetuses with congenital heart disease between 2000 and 2005 in comparison to a previous multicentre study regarding the period 1983-1996. PARTICIPANTS AND METHODS: Data of seven centres were prospectively collected, the inclusion criteria being a confirmed fetal diagnosis after birth or at autopsy and a known follow-up, for at least 6 months after birth. Data of 649 fetuses, median age at diagnosis 24 weeks' gestation (15-37), 340/649 (52.4%) diagnosed before 24 weeks, were analysed. RESULTS: Sixty seven and 59 cases had chromosomal or extracardiac anomalies (10.3 and 9.1%). Termination of pregnancy was chosen in 21.6% of cases versus 28.9% in the previous study, being significantly lower in cases with early diagnosis (P <0.001). Out of 509 fetuses continuing pregnancy, 23 died in utero (4.5%) and 110 (21.1%) postnatally, versus 43% in the previous study (P <0.0017). Total surgical/postprocedure death occurred in 20.6% (59/287 infants) versus 37% previously (P <0.003), 67 infants being premature and 35 with associated chromosomal or extracardiac anomalies. The current overall mortality rate was higher in cases with chromosomal or extracardiac anomalies (59.5 and 51.35%, respectively, whereas it was 20.1% in isolated congenital heart disease). Overall current survival was 376 of 509 (73.9%) versus 45% in the previous study (P <0.0001). CONCLUSION: Our data show a reduced overall and surgical mortality, with respect to our previous study, resulting from resulting from an improved perinatal management and treatment of affected fetuses in the more recent era.

Physical counter-pressure manoeuvres in preventing syncopal recurrence in patients older than 40 years with recurrent neurally mediated syncope: a controlled study from the Third International Study on Syncope of Uncertain Etiology (ISSUE-3)†.

AIMS: Physical counter-pressure manoeuvres (PCM) are effective in young patients with vasovagal syncope and recognizable prodromal symptoms. The aim of this study was to investigate their effectiveness in patients ≥40 years with severe neurally mediated syncope (NMS) enroled in the Third International Study on Syncope of Uncertain Etiology (ISSUE-3). METHODS AND RESULTS: In the ISSUE-3 study, 63 out of 162 patients had a diagnosis of hypotensive NMS (Types 2, 3, and 4A) documented by implantable loop recorder; of these, 40 were instructed to perform isometric leg and arm PCM therapy. Their mean age was 62 ± 13 years; 47% of patients had a history of some episodes without prodrome. A group of 45 untreated patients acted as controls. The primary endpoint was the time to first syncope recurrence. During follow-up, syncope recurred in 15 PCM patients (37%) and in 24 control patients (53%) (P = 0.14). At 21 months, the modelled syncope recurrence rates were 42% [95% confidence interval (CI): 27-61] and 64% (95% CI: 48-80), respectively (P = 0.27). CONCLUSION: In conclusion, many ISSUE-3 patients affected by hypotensive NMS have syncopal recurrence despite PCM. Older age and the absence of sufficiently long recognizable prodromal symptoms in the ISSUE-3 population might have hampered the effectiveness of PC therapy.

Cardiac resynchronisation therapy associated with pulmonary artery banding in an adult with severe right ventricular dysfunction after Mustard repair for complete transposition of the great arteries: results after 2 years of follow-up.

Late dysfunction of the systemic right ventricle in patients with complete transposition of the great arteries after Mustard or Senning procedures and progressive deterioration of the clinical status has been demonstrated. However, evidence-based data on the effective therapy for systemic right ventricular dysfunction in these patients are yet to be defined. Our patient shows an improvement in the right ventricular systolic function, with a reduction in tricuspid regurgitation and a consequent better exercise tolerance after a hybrid approach consisting of an upgrading of a previous transvenous-implanted dual-chamber Implantable Cardiac Defibrillator to biventricular pacing associated with pulmonary artery banding via an anterior thoracotomy.

Long-term results of treatment with bosentan in adult Eisenmenger's syndrome patients with Down's syndrome related to congenital heart disease.

BACKGROUND: Patients with Down's syndrome and shunt lesions are at high risk of developing pulmonary arterial hypertension (PAH) earlier than patients without Down's syndrome. However, data on the efficacy of PAH-specific therapy in patients with Down's syndrome are limited. The aim of this retrospective analysis was to determine the long-term efficacy of the dual endothelin receptor antagonist, bosentan, in Eisenmenger's syndrome (ES) patients with Down's syndrome. METHODS: In this observational study adults with Down's syndrome with a confirmed diagnosis of ES (World Health Organization functional class III) and receiving bosentan therapy and were followed up long term. Clinical evaluation at baseline and follow-up visits included resting transcutaneous arterial oxygen saturation and laboratory assessments. Exercise capacity was evaluated using a 6-minute walk test where transcutaneous arterial oxygen saturation at peak exercise (SpO2), 6-minute walk distance (6MWD) and Borg dyspnoea index were assessed. A full echocardiographic assessment was conducted at baseline and follow-up visits. RESULTS: Overall, seven adults (mean age 29.6 ± 11.2 years; 57% male) received bosentan at a starting dose of 62.5 mg twice daily. This was increased to the target dose of 125 mg twice daily 4 weeks later. All patients remained on bosentan until the end of the study. After a mean (± standard deviation) duration of 52.2 ± 3.9 months (range: 46.0-55.5 months), 6MWD had increased from 199.6 ± 69.1 metres to 303.7 ± 99.9 metres (P < 0.05) and SpO2 at the end of the 6-minute walk test had increased from 61.6 ± 7.6% to 74.7 ± 6.2% (P < 0.05). Echocardiography demonstrated a significant change in acceleration time from 62.9 ± 11.6 m/s to 83.0 ± 9.6 m/s (P = 0.0156), and acceleration time/ejection time ratio from the pulmonary flow from 0.24 ± 0.04 at baseline to 0.30 ± 0.02 (P = 0.0156) at final follow-up. CONCLUSIONS: Long-term treatment with bosentan significantly improved exercise capacity and oxygen saturation following exercise in adult ES patients with Down's syndrome. These data confirm that the presence of Down's syndrome does not affect the response to oral bosentan therapy.

Cupryphans, metal-binding, redox-active, redesigned conopeptides.

Contryphans are bioactive peptides, isolated from the venom of marine snails of the genus Conus, which are characterized by the short length of the polypeptide chain and the high degree of unusual post-translational modifications. The cyclization of the polypeptide chain through a single disulphide bond, the presence of two conserved Pro residues, and the epimerization of a Trp/Leu residue confer to Contryphans a stable and well-defined structure in solution, conserved in all members of the family, and tolerant to multiple substitutions. The potential of Contryphans as scaffolds for the design of redox-active (macro)molecules was tested by engineering a copper-binding site on two different variants of the natural peptide Contryphan-Vn. The binding site was designed by computational modeling, and the redesigned peptides were synthesized and characterized by optical, fluorescence, electron spin resonance, and nuclear magnetic resonance spectroscopy. The novel peptides, named Cupryphan and Arg-Cupryphan, bind Cu(2+) ions with a 1:1 stoichiometry and a K(d) in the 100 nM range. Other divalent metals (e.g., Zn(2+) and Mg(2+)) are bound with much lower affinity. In addition, Cupryphans catalyze the dismutation of superoxide anions with an activity comparable to other nonpeptidic superoxide dismutase mimics. We conclude that the Contryphan motif represents a natural robust scaffold which can be engineered to perform different functions, providing additional means for the design of catalytically active mini metalloproteins.

Conus ventricosus venom peptides profiling by HPLC-MS: a new insight in the intraspecific variation.

Conus is a genus of predatory marine gastropods that poison the prey with a complex mixture of compounds active on muscle and nerve cells. An individual cone snail's venom contains a mixture of pharmacological agents, mostly short, structurally constrained peptides. This study is focused on the composition of the venom employed by Conus ventricosus Gmelin, 1791, a worm-hunting cone snail living in the Mediterranean Sea. For this purpose, LC coupled to MS techniques has been successfully used to establish qualitative and quantitative differences in conopeptides from minute amounts of venom ducts. We were able to prove variability in the venom conopeptide complement, possibly related to different trophic habits of the species in the Mediterranean Sea. Moreover, the information-rich MS techniques enabled us to identify two novel C. ventricosus peptides, here named Conotoxin-Vn and -Conotoxin-Vn. On the basis of the structural data collected so far, we suggest that Conotoxin-Vn is a conopeptide belonging to the -family that recognizes calcium channels through a specific pharmacophore. Similarly, molecular modeling data suggest that -Conotoxin-Vn should represent a competitive antagonist of neuronal nicotinic acetylcholine receptors (nAChRs).

Factors affecting left ventricular remodelling and mechanics in the long-term follow-up after successful repair of aortic coarctation.

AIMS: To identify factors predisposing to abnormal left ventricular geometry and mechanics in 52 patients after successful repair of aortic coarctation. METHODS AND RESULTS: We evaluated left ventricular remodelling, systolic midwall mechanics, and isthmic gradient by echo-Doppler, systemic blood pressure at rest/exercise and by ambulatory blood pressure monitoring, and the aortic arch by magnetic resonance imaging. Echocardiographic findings were compared with those of 142 controls. The patients with aortic coarctation showed an increased indexed left ventricular end-diastolic volume, increased mass index, increased ratio of mass to volume and systolic chamber function. The contractility, estimated at midwall level, was increased in 21 percent of the patients. In 26 (50 percent) of the patients, we found abnormal left ventricular geometry, with 9 percent showing concentric remodelling, 33 percent eccentric hypertrophy, and 8 percent concentric hypertrophy. These patients were found to be older, underwent a later surgical repair, and to have higher systolic blood pressures at rest and exercise as well as during ambulatory monitoring. The relative mural thickness and mass index of the left ventricle showed a significant correlation with different variables on uni- and multivariate analysis. Age and diastolic blood pressure at rest are the only factors associated with abnormal left ventricular remodelling. CONCLUSIONS: Patients who have undergone a seemingly successful surgical repair of aortic coarctation may have persistently abnormal geometry with a hyperdynamic state of the left ventricle. This is more frequent in older patients, and in those with higher diastolic blood pressures.

Solution structure of the cyclic peptide contryphan-Vn, a Ca2+-dependent K+ channel modulator.

The solution structure of contryphan-Vn, a cyclic peptide with a double cysteine S-S bridge and containing a D-tryptophan extracted from the venom of the cone snail Conus ventricosus, has been determined by NMR spectroscopy using a variety of homonuclear and heteronuclear NMR methods and restrained molecular dynamics simulations. The main conformational features of backbone contryphan-Vn are a type IV beta-turn from Gly 1 to Lys 6 and a type I beta-turn from Lys 6 to Cys 9. As already found in other contryphans, one of the two prolines--the Pro4--is mainly in the cis conformation while Pro7 is trans. A small hydrophobic region probably partly shielded from solvent constituted from the close proximity of side chains of Pro7 and Trp8 was observed together with a persistent salt bridge between Asp2 and Lys6, which has been revealed by the diagnostic observation of specific nuclear Overhauser effects. The salt bridge was used as a restraint in the molecular dynamics in vacuum but without inserting explicit electrostatic contribution in the calculations. The backbone of the unique conformational family found of contryphan-Vn superimposes well with those of contryphan-Sm and contryphan-R. This result indicates that the contryphan structural motif represents a robust and conserved molecular scaffold whose main structural determinants are the size of the intercysteine loop and the presence and location in the sequence of the D-Trp and the two Pro residues.