Nailfold capillaroscopy reveals early peripheral microcirculation abnormalities in children affected by heterozygous familial hypercholesterolemia.

BACKGROUND: nailfold capillaroscopy (NCF) is a non-invasive imaging technique to seek peripheral microcirculation abnormalities in children and adults. Familial hypercholesterolemia is a genetic disorder caused by mutations capable of increasing blood levels of low-density lipoproteins cholesterol (LDL-C), thus triggering early atherosclerosis. The study aims at evaluating peripheral microcirculation in children with heterozygous familial hypercholesterolemia (HeFH) by means of NFC in comparison with healthy peers and at searching for possible correlations between these abnormalities and patients' lipid panel. METHODS: thirty-six HeFH patients were enrolled (13 males and 23 females. Mean age 8 ± 3 years; age range 3-13 years). They had increased levels of total cholesterol (237.9 ± 34.2 mg/dl) and LDL-C (154.2 ± 37.6 mg/dl). Both values were ≥95th gender and age specific centile. All the subjects in the study underwent NFC. RESULTS: In 69.4 % of HeFH children nailfold capillaries were tortuous (p < 0.00001 compared to healthy controls). In 41.6 % the number of capillaries was markedly reduced (<7 capillaries/mm). The mean number of capillaries was 8.4 ± 2.6/mm in HeFH and 12.2 ± 1.4/mm in healthy controls (p < 0.00001). In 100 % of the sample size capillary blood flow was slowed down (p < 0.00001). In 50 % of the sample size a blood "sludge" phenomenon was seen (p < 0.00001). No gender differences were detected. Sludge phenomenon was seen only in those with LDL-C over 99th centile (p < 0.00001). CONCLUSION: NCF allows the identification of an early peripheral microvascular dysfunction in HeFH children which is similar to that already seen in atherosclerotic disease. Prompt identification of these capillary abnormalities may be crucial in implementing early prevention measures.

A novel ultrafast-low-dose computed tomography protocol allows concomitant coronary artery evaluation and lung cancer screening.

BACKGROUND: Cardiac computed tomography (CT) is often performed in patients who are at high risk for lung cancer in whom screening is currently recommended. We tested diagnostic ability and radiation exposure of a novel ultra-low-dose CT protocol that allows concomitant coronary artery evaluation and lung screening. METHODS: We studied 30 current or former heavy smoker subjects with suspected or known coronary artery disease who underwent CT assessment of both coronary arteries and thoracic area (Revolution CT, General Electric). A new ultrafast-low-dose single protocol was used for ECG-gated helical acquisition of the heart and the whole chest. A single IV iodine bolus (70-90 ml) was used. All patients with CT evidence of coronary stenosis underwent also invasive coronary angiography. RESULTS: All the coronary segments were assessable in 28/30 (93%) patients. Only 8 coronary segments were not assessable in 2 patients due to motion artefacts (assessability: 98%; 477/485 segments). In the assessable segments, 20/21 significant stenoses (> 70% reduction of vessel diameter) were correctly diagnosed. Pulmonary nodules were detected in 5 patients, thus requiring to schedule follow-up surveillance CT thorax. Effective dose was 1.3 ± 0.9 mSv (range: 0.8-3.2 mSv). Noteworthy, no contrast or radiation dose increment was required with the new protocol as compared to conventional coronary CT protocol. CONCLUSIONS: The novel ultrafast-low-dose CT protocol allows lung cancer screening at time of coronary artery evaluation. The new approach might enhance the cost-effectiveness of coronary CT in heavy smokers with suspected or known coronary artery disease.

Antiplatelet therapy in elderly patients with acute coronary syndrome: Between scientific evidence and future perspectives.

Dual antiplatelet therapy (DAPT) is an important strategy for reducing cardiovascular events (CV) after an acute coronary syndrome (ACS). Elderly patients undergoing DAPT have a higher risk of bleeding than younger patients for a variety of reasons. Stratification of thrombotic/hemorrhagic risk is mandatory in order to decide on the type and duration of DAPT. The percentage of patients ≥ 75 years represented in clinical trials is not large, so very often elderly people are prescribed treatment protocols only experimented on younger patients with a lower hemorrhagic risk. However, even in patients aged ≥ 75 treated with invasive or conservative therapy, after an ACS, a DAPT with aspirin 80-100 mg/day plus a P2Y12 receptor inhibitor for 12 months is recommended. In elderly patients, DAPT should be considered a dynamic process that can be modified over time based on the patient's clinical conditions, or any other necessities (non-procrastinating surgical interventions, comorbid-like effects that can increase hemorrhagic risk). In patients with moderate-high or very high hemorrhagic risk, DAPT treatment should last less than 12 months. A prolongation of DAPT beyond 12 months in this setting is limited to a very low percentage of patients, after careful assessment of ischemic/hemorrhagic profile.

The Association between Mid-Upper Arm Circumference and Blood Pressure in an Italian Population of School-Aged Children and Adolescents with Lipid Disorders.

Background: Many anthropometric measurements have been investigated concerning their association with blood pressure (BP) in paediatric age groups. This study aims to find a relationship between mid-upper arm circumference (MUAC) and BP in a population of children and adolescents aged 1-18 years. Methods: 5853 subjects (2977 females and 2876 males) were studied. MUAC, body mass index (BMI), and BP were measured. The individuals in the study were subdivided and grouped by gender and type of school attended in Italy: 1-5 years (pre-school), 6-10 years (primary school), 11-13 years (secondary school), 14-18 years (high school). Results: In the age range of 6-13 years, all the subjects with MUAC > 50th percentile had systolic and diastolic BP significantly higher than children with MUAC below 50th percentile (p < 0.0001). In the age range 14-18 years, the relationship persisted only in females (p < 0.001 and p < 0.05 for diastolic and systolic BP, respectively). A linear relationship was found between MUAC and BMI. Conclusions: In Italian children of both genders aged 6-13, arm distribution of body fat is strongly associated with increased systolic and diastolic BP. As such, a simple anthropometric measurement like MUAC might represent a tool to identify young subjects who are at risk for HTN.

Apolipoprotein B and Lipid Profile in Italian Children and Adolescents.

RATIONALE: The prevention of cardiovascular (CV) disease is mandatory from childhood onwards. Among biochemical markers related to the clinical cardiovascular outcome, LDL cholesterol (LDL-C), non-HDL-C and apolipoprotein B (ApoB) are recognized as main target parameters. Emphasis on ApoB concentrations is growing, as representative of any class of atherogenic lipoprotein. This consideration allows checking of subjects under 18 years of age when the CV risk occurs. The aim of this study is to evaluate ApoB levels in a sample of Italian hyperlipidemic children and adolescents, and their siblings, to test any relationship with their lipid profile. METHODS: A retrospective study, including 1877 children and adolescents (aged 0-18 years), was performed. Clinical and biochemical data were selected from a database, including the lipid profile, ApoB analysis and anthropometric parameters of any proband. Participants had been checked as potentially hyperlipidemia affected, the suspicion raised by familial CV risk or because the dyslipidemia was already known. Data from the first visit at the University Hospitals in Rome and Turin were collected. Patients affected by secondary hyperlipidemia or obesity were excluded. Blood test analysis was performed in fasting conditions by automated commercial kits. Participants were classified according to gender, age (stratified in subgroups: 0-5, 6-10, 11-14, and 15-18 years old) and anthropometric parameters, referred to as weight in Kg and height in cm, and BMI calculated. Lipid profile results were stratified in relation to acceptable, borderline, or increased levels, as indicated by NCEP, and any potential relation with ApoB established. Statistics were performed by Epi-Info 7 programs to evaluate the variance analysis. Either parent could sign the informed consent. RESULTS: Among the whole sample n.1010 and n.867 participants were females and males, respectively. TC values acceptable (≤170 mg/dL), borderline (171-200 mg/dL) and elevated (≥201 mg/dL) were found in 411 (22%), 585 (31%) and 881 (47%) participants, respectively. The LDL-C cut-off considered was 110 mg/dL (90° percentile). Mean ApoB progressively increased from 65 to 110 mg/dL according to TC levels and resulted in significant correlation when any age subgroup and gender was considered. The highest ApoB values, TC and LDL-C related, were found in the youngest subgroup, regardless of gender. CONCLUSION: ApoB results increase progressively and in parallel with TC and LDL-C and represent a further parameter to distinguish between normal and hyperlipidemic subjects. Serum levels are close to 70 mg/dL and to 100 mg/dL in the former and latter group, respectively.

Clopidogrel plus indobufen in acute coronary syndrome patients with hypersensitivity to aspirin undergoing percutaneous coronary intervention.

The prescription of aspirin (acetylsalicylic acid (ASA)) to patients with a history of hypersensitivity to this drug could prove harmful. The aim of the study was to assess the antiplatelet activity and safety of a combined antiplatelet treatment with indobufen and clopidogrel in acute coronary syndrome (ACS) patients with hypersensitivity to aspirin, undergoing coronary stenting. Forty-two consecutive ACS patients treated with stent implantation were randomly assigned to receive clopidogrel 75 mg daily (loading dose 300 mg) plus indobufen 100 mg twice a day (group A), or clopidogrel 75 mg daily, after 300 mg of loading dose (group B). Platelet activity and safety were monitored in both groups at 1, 3, 6, 12, and 18 months with laboratory and clinical evaluation. A lower value of max % platelet aggregation to arachidonic acid and collagen was found in group A compared to group B (31.79 ± 27.33 vs. 73.67 ± 19.92; p < 0.0001 and 28.53 ± 21.32 vs. 73.58 ± 17.71; p < 0.0001, respectively). There was no difference in max % of platelet inhibition to adenosine diphosphate between the two groups (14.23 ± 18.92 vs. 10.30 ± 18.97; p = 0.23). In the population that was under indobufen treatment, the serum thromboxane B2 (TXB2) production at 1 week and 1 month was very low (2.6 ± 1.6 ng/ml and 3.0 ± 2.7 ng/ml, respectively; p = 0.82). The combined treatment was well tolerated in group A patients. This study suggests that the combined antiplatelet treatment with clopidogrel and indobufen could be a good option in ACS patients with hypersensitivity to aspirin undergoing coronary stenting.

Myocardial Metastasis of Tongue Cancer: A Rare Localization.

BACKGROUND Cardiac metastases of head and neck tumors are extremely rare, and antemortem diagnosis is even rarer. In most cases, patients show symptoms or electrocardiographic abnormalities and expected survival is considerably low. CASE REPORT A 72-year-old man was admitted to our cardiology ward with suspected endocarditis 2 months after a right hemiglossectomy for a squamous cell carcinoma. He was asymptomatic and showed no electrocardiogram abnormalities. Echocardiography showed an iso-ipoechogenic round-shaped formation at the right ventricle apex that was suspected to be a metastasis owing to 2 cardiac magnetic resonance imaging examinations showing a significant increase in its volume over 14 days. The patient was evaluated by a multidisciplinary team and referred for first-line chemotherapy with carboplatin, 5-fluoruracil, and cetuximab. He died after almost 4 months of follow-up. CONCLUSIONS This case presents a very rare diagnosis as well as some unique features, including the intramyocardial localization, the absence of symptoms, and electrocardiogram abnormalities. Our report shows the relevance of imaging techniques in defining even the most unusual clinical findings, and it emphasizes the significance of early recognition of cardiac masses in order to identify the appropriate medical or surgical therapy for patients.

Acute atrial ischemia associates with early but not late new-onset atrial fibrillation in STEMI patients treated with primary PCI: relationship with in-hospital outcomes.

BACKGROUND: New-onset atrial fibrillation (NOAF), both early (EAF) or late (LAF), may complicate ST-segment elevation myocardial infarction (STEMI). The mechanisms underlying EAF or LAF are poorly described. We investigated atrial branch occlusion and EAF or LAF onset in STEMI patients undergoing primary percutaneous coronary intervention. METHODS: This was a retrospective cohort study including 155 STEMI patients. Patients were divided into 3 groups: sinus rhythm (SR), EAF, or LAF. Clinical characteristics, angiographic features including occlusion of atrial branches, namely ramus ostia cavae superioris (ROCS), atrio-ventricular node artery (AVNA), right intermediate atrial artery (RIAA), and left intermediate atrial artery, were assessed. We also investigated in-hospital adverse events (AEs) and death. RESULTS: Mean age was 63.8±11.9 years; 78.7% were men. NOAF was detected in 22 (14.2%) patients: 10 (6.4%) EAF and 12 LAF (7.7%). Compared to EAF, LAF patients were older (p=0.013), with higher GRACE risk score (p=0.014) and Killip class (p=0.015), depressed ejection fraction (p=0.007), elevated filling pressures (p=0.029), higher C-reactive protein (p=0.014) and more with thrombolysis in myocardial infarction flow <3 (p=0.015). Compared to SR, EAF was associated with higher prevalence of occluded ROCS (p=0.010), AVNA (p=0.005), and RIAA (p<0.001). Moreover, EAF patients had more frequently ≥2 diseased atrial branches than SR (19.5%, p<0.001) and LAF (25%, p<0.030) patients. LAF patients had a higher in-hospital AEs (p=0.019 vs SR; p=0.029 vs EAF) and death (p=0.004 vs SR). CONCLUSIONS: The occlusion of atrial branches is associated with EAF but not LAF following STEMI. LAF patients had worse in-hospital AEs and mortality.

Concomitant screening of coronary artery disease and lung cancer with a new ultrafast-low-dose Computed Tomography protocol: A pilot randomised trial.

We performed a pilot randomised study to assess the feasibility and radiation exposure of a new computed tomography (CT) protocol that allows screening of both coronary artery disease (CAD) and lung cancer. Current or former heavy smokers at high lung cancer risk with indication to cardiac CT for suspected or known CAD were randomised to undergo concomitant CT evaluation of either cardiac or thoracic area or cardiac CT only. Out of 129 subjects deemed eligible for the study, 110 agreed to participate and were randomised to simultaneous cardiac and lung CT (Gr.A; n = 55) or cardiac CT only (Gr.B; n = 55). The feasibility (i.e. adequate visualization of coronary artery segments) was noninferior with simultaneous cardiac and lung CT compared with the standard cardiac CT (870 of 889 segments [97%] in Gr.A vs 878/890 segments [99%] in Gr.B; mean difference 2.0% [90% confidence interval: -0.3% to 4.1%]). The safety (i.e. effective radiation dose) of the concomitant cardiac and lung CT protocol was noninferior to the standard cardiac CT (1.5 [95% confidence intervals: 1.2-1.7] vs. 1.4 [95% confidence intervals: 1.1-1.6] mSv; mean difference 0.1 mSv [90% confidence interval: -0.2 to 0.3 mSv]). In the two groups, a total of 25 significant (>70%) coronary stenoses were found at cardiac CT (9/55 cases of Gr.A vs 11/55 cases of Gr.B). Pulmonary nodules >2 mm were detected in 7 of the 55 Gr.A subjects. This pilot randomised study shows that concomitant CAD and lung cancer screening by means of a new CT protocol is both feasible and safe, thus allowing a comprehensive evaluation of both cardiac and thoracic regions during one CT scanning only. (ClinicalTrials.gov Identifier: NCT03727958).

[The importance of defining methodology for post-marketing observational studies on cardiovascular therapies]. / L'importanza della metodologia negli studi post-marketing delle terapie cardiovascolari.

In recent years, a growing number of observational studies in cardiology have been carried out following the criticism that rigid design of randomized clinical trials produces information that is not applicable to the general patient. This approach is very common in several branches of medicine, first of all oncology, but has often been considered marginal in cardiology. The recent introduction of new oral anticoagulants (NOACs) on the market, however, has seen a proliferation of "real-life" studies, drawing the attention of cardiologists to the advantages and limitations of post-marketing studies. NOACs have been approved for use on the basis of large randomized clinical trials that have clearly documented their efficacy and safety. Since they have become available, the analysis of phase IV data has been considered crucial and therefore a great amount of information on the use of NOACs in daily practice has become available. It should be considered, however, that the possibility exists that results obtained from "real-world" studies, which do not apply rigid scientific criteria, may lead to incorrect conclusions. Accordingly, it is mandatory to fully define the operational standards of observational studies. All the protagonists of post-marketing analysis (physicians, epidemiologists, pharmacologists, statisticians) should handle the data strictly in order to ensure their reliability and comparability with other studies. To this end, it is crucial that researchers follow rigorous operational protocols for phase IV studies. Briefly, any "real-life" study should be prospective and adhere to what is prespecified by the research protocol - which must illustrate the background and rationale of the study, define its primary endpoint, and detail the methods, i.e. study design, population and variables.

Two cases of acute chest discomfort and the Central Italy earthquake.

We present the cases of two postmenopausal women presenting to our emergency department with acute chest discomfort soon after the Central Italy earthquake. Different diagnoses were made in the two patients. The role of the earthquake as a stressful event triggering diverse chest pain syndromes is discussed.

Ivabradine in Patients with ST-Elevation Myocardial Infarction Complicated by Cardiogenic Shock: A Preliminary Randomized Prospective Study.

BACKGROUND AND OBJECTIVE: An elevated heart rate (HR) is an independent risk factor for mortality and morbidity in patients with acute heart failure (HF). The purpose of this study was to evaluate the impact of ivabradine, a selective HR-lowering agent, in patients with cardiogenic shock (CS) complicating ST-elevation acute myocardial infarction (AMI). METHODS: Patients with post-AMI CS were randomized to standard treatment (SDT, 28 patients) or to standard treatment plus ivabradine (I + SDT, 30 patients). In the presence of orotracheal intubation (OTI), ivabradine was administered by nasogastric intubation. HR, BP, New York Heart Association (NYHA) class, NT-proBNP, left ventricular ejection fraction (LVEF) and diastolic function (LVDF) were monitored at specific times after the onset of AMI. The primary (surrogate) end-point was the in-hospital halving of plasma NT-proBNP levels. The secondary end-points were cardiovascular death, hospital re-admission for worsening HF, and clinical and haemodynamic improvement. RESULTS: Treatment groups were statistically similar with regard to age, gender distribution, cardiovascular risk factors, number of diseased vessels and overall treated lesions, AMI site and occurrence of OTI. In-hospital mortality was double in the SDT group in comparison with the I + SDT group (14.3 vs. 6.7 %), but the difference was not statistically significant. HR, BP, NT-proBNP and LVEF favorably changed in both groups, but the change was more relevant in the I + SDT group. LVDF significantly changed only in the I + SDT group (p < 0.01). Patients in the I + SDT group did not experience adverse effects. CONCLUSION: Ivabradine in CS complicating AMI is safe, is associated with a short-term favourable outcome and can be effectively administered by nasogastric intubation.

Myocardial cytoprotection by trimetazidine against anthracycline-induced cardiotoxicity in anticancer chemotherapy.

The ability of trimetazidine (2,3,4, trimethoxybenzylpiperazine dihydrochloride, TMZ) to protect the myocardium against anthracycline (ANT)-induced cardiotoxicity during chemotherapy has been evaluated in female patients with breast cancer. A clinical trial was conducted in 61 patients subdivided into three groups: group 1 (n = 15, G1 ) treated with standard ANT protocol and cardioprotection by dexrazoxane (DEX) plus TMZ (60 mg, daily dose); group 2 (n = 22, G2) treated with ANT and cardioprotection by TMZ only; and group 3 (n = 24, G3) scheduled to receive ANT therapy and DEX. All the patients submitted to an echocardiographic evaluation of diastolic function (E wave velocity, A wave velocity, isovolumetric relaxation time [IVRT], deceleration time [DT]) at enrollment (T0), at T1 time, at T2 time, and at T3 time. After a 12-month follow-up period, the patients showed a good conservation of diastolic function both in G1 and G2 groups. No statistically significant difference was observed in E wave and A wave velocity and E/A ratio after ANT treatment. TMZ produced a cardioprotective effect, comparable to DEX protection, against subacute and chronic subclinical cardiotoxicity with no significant changes in diastolic function after 1 year of follow-up.

Effectiveness of two-year clopidogrel + aspirin in abolishing the risk of very late thrombosis after drug-eluting stent implantation (from the TYCOON [two-year ClOpidOgrel need] study).

It remains unclear whether dual antiplatelet therapy >12 months might carry a better prognosis after percutaneous coronary intervention (PCI) with drug-eluting stents (DESs). To address the hypothesis that in the real world the risk of very late thrombosis after PCI with DESs can be decreased by an extended use of clopidogrel, we set up the Two-Year ClOpidOgrel Need (TYCOON) registry and prospectively investigated the impact on very late thrombosis of 12- versus 24-month dual antiplatelet regimens in an unselected population. The registry enrolled 897 consecutive patients who underwent PCI with stenting from January 1, 2003, to December 31, 2004, and had dual antiplatelet therapy. All patients had a 4-year clinical follow-up. In the 447 patients with DES implantation, the dual antiplatelet regimen after PCI was given for 12 months in the 173 patients treated in 2003 (12-month group) and for 24 months in the 274 patients treated in 2004 (24-month group). Comparison between groups did not reveal any significant difference in baseline clinical characteristics, angiographic and procedural features, and major adverse cardiac events. During follow-up, there were 5 cases of stent thrombosis after PCI in the 12-month DES group and 1 case in the 24-month DES group (p = 0.02). Specifically, there were 2 cases of subacute thrombosis (1 in each group), no case of late thrombosis, and 4 cases of very late thrombosis occurring at 13, 15, 17, and 23 months after DES implantation in the 12-month group only. In conclusion, a 2-year dual antiplatelet regimen with aspirin and clopidogrel can prevent the occurrence of very late stent thrombosis after PCI with DESs.

Clinical results of two year dual antiplatelet therapy after primary percutaneous coronary intervention with paclitaxel-eluting stents: a single centre study.

AIMS: The long-term outcome of extended dual antiplatelet therapy after percutaneous coronary intervention (PCI) is unexplored. The purpose of the study was to evaluate the 2 year safety and efficacy of continuous dual antiplatelet treatment in patients undergoing primary PCI with paclitaxel-eluting stent (PES) for acute ST segment elevation myocardial infarction (STEMI). METHODS AND RESULTS: A series of 145 consecutive patients with STEMI underwent primary PCI with PES. All patients received intracoronary high dose bolus and 24 hours i.v. infusion of tirofiban and were then treated with dual anti-aggregation up to 2 years. The incidence of major adverse cardiac events (MACE) was evaluated at 1 month, 1 year, and 2 years during the follow-up period. Overall, the rate of cumulative MACE detected at follow-up was 2.7%, with a 1.4% incidence of mortality and a 0.7% need for target vessel revascularisation. No major bleeding occurred during follow-up (95% C.I. 0-2.6%). Safety analysis revealed that minor bleeding occurred in 5 patients (3.4%) at the time of PCI, and that thrombocytopenia developed in 3 patients (2.1%) with the extended clopidogrel course. During the 2 year follow-up, in-stent thrombosis was seen in only 1 patient who stopped drug treatment against medical advice, but did not occur in patients who remained on dual antiplatelet therapy. CONCLUSIONS: This study shows in a 'real world' scenario that sustained dual antiplatelet therapy following primary PCI with PES in patients with STEMI is associated with very good 2 year clinical results.

Ambulatory pulse pressure, left ventricular hypertrophy and function in arterial hypertension.

BACKGROUND: A wide pulse pressure (PP) can provide important risk assessment information about myocardial infarction, carotid artery atherosclerosis, and global cardiovascular risk. Ambulatory pulse pressure (APP) does not have a well-known prognostic value in hypertensive patients. METHODS: To evaluate the relationship among high APP, atrial volumes, and cardiac function, an observational study was performed on 108 untreated non-elderly hypertensive patients (mean age 54.23 +/- 7.12). Twenty-four-hour ambulatory blood pressure monitoring, Doppler and echocardiographic measurements of systolic, diastolic function, left and right atrial volumes, left ventricular mass index and dimensions, were performed in subjects with both clinic and APP > 60 mmHg (APP1 Group). A control group of hypertensive selected subjects with both clinic and APP < 60 mmHg was chosen (APP 2 Group). RESULTS: The APP1 group showed left atrial volume enlargement, high left ventricular mass index, and impaired diastolic function. A positive correlation was found in the APP1 group results among left ventricular end diastolic diameter (r = 0.39, P < 0.01), left atrial volume (0.38, P < 0.05), and left ventricular mass index (r = 0.33, P < 0.05); clinic PP showed a statistically significant correlation with left atrial volume, left ventricular end diastolic diameter, and left ventricular mass index only in the APP1 group. CONCLUSIONS: These results suggest that elevated APP can be considered an effective predictor of cardiovascular risk in hypertensive subjects. In these patients echocardiographic evaluation of left ventricular function and morphology can increase the prognostic value of PP.