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Background : Chronic obstructive pulmonary disease (COPD) is associated with subclinical atherosclerosis and endothelial dysfunction, which can be assessed non-invasively through flow-mediated dilation (FMD). In this study, we evaluated the potential impact of inhaled corticosteroid (ICS) therapy on FMD of COPD patients undergoing pulmonary rehabilitation (PR). Methods : Medical records of COPD patients undergoing FMD assessment upon admission to our Pulmonary Rehabilitation Unit were reviewed in this retrospective post hoc analysis. Results : A total of 46 patients with COPD (median age 71.5 years, 28.3% postmenopausal females) were included in the final analysis. Among these, 27 participants were currently receiving ICS therapy, while 19 were not. At baseline, the two groups showed no difference in the main clinical and functional variables. Similarly, no significant difference was observed in vascular reactivity parameters, with a median FMD of 3.12% (IQR: 2.23-4.45) in ICS users and 3.39% (IQR: 2.45-4.08) in ICS nonusers ( p = 0.544). After PR, a significant improvement in the main rehabilitation and patient-reported outcomes was observed in all groups, with a significant improvement in FMD documented in both patients treated with steroids (from 3.12%; IQR: 2.23-4.45 to 4.77%; IQR: 3.25-5.63, p = 0.022) and in those who were not (from 3.39%; IQR: 2.45-4.08 to 5.04%; IQR: 3.98-6.06, p = 0.005). FMD changes were of comparable magnitude among groups. Conclusions : Our preliminary findings do not indicate a significant impact of medications containing ICS on the endothelial function of COPD patients, suggesting that the potential beneficial effect of PR on this surrogate marker of cardiovascular risk is independent of inhaled therapy.

Background: Aortitis is a rare inflammation of the aorta. It can be classified as infective, non-infective, or idiopathic. Infective aortitis can debut as an acute aortic syndrome that needs urgent or emergent treatment. Historically, these kinds of patients have been preferably treated by open surgery, with subsequent lack of information about the endovascular repair. The aim of the present study is to report the results of our experience with the urgent or emergent endovascular repair of infective aortitis with acute presentation. Methods: All consecutive urgent or emergent endovascular repairs, performed between January 2019 and January 2024 for the treatment of infective aortitis, were included. The inclusion criteria were clinical, laboratory, and radiological findings recognized as aortitis risk factors. Patients with graft or endograft infection, aortic fistulae, and mycotic aneurysm were excluded. Primary endpoints were technical success and 30-day and follow-up survival. Early and late major adverse events, any changes in lesion morphology over time, and need for re-intervention were also assessed. Results: A total of 15 patients (14 males and 1 female) with a mean age of 74.2 ± 8.3 were included. All the subjects were treated by endovascular means in an urgent or emergent setting because of a rapidly growing aneurysm, symptomatic lesion, or contained or free aortic rupture. The diagnosis of infective aortitis was confirmed postoperatively by positive blood cultures in all the patients. A rapidly growing or symptomatic lesion was noted in all 15 subjects. Among these there were six (40%) contained and two (13%) free aneurysm ruptures. The endovascular techniques performed were as follows: four thoracic-EVAR (TEVAR), three off-the-shelf branched-EVAR (BEVAR), one Chimney-EVAR (Ch-EVAR), six EVAR with bifurcated graft, and one EVAR with straight tube graft. Technical success was achieved in 100% of the patients. Two patients (13%) died within 30 days after the index procedure. No case of early aortic-related mortality was registered. During a mean follow-up of 31.6 ± 23.1 months (range 1-71), no further death or major adverse event was registered among the remaining 13 alive patients. Re-interventions were performed in three cases (20%). Aneurysm's shrinkage > 5 mm or stability was noted in 10 of the 13 patients who survived the early period after repair. Conclusions: Despite the relative reluctance to use an endograft in an infected area, in our experience the endovascular approach resulted to be feasible, safe, and effective in the treatment of infective aortitis with acute presentation, with acceptable peri-operative and mid-term follow-up outcomes. Further studies are needed to confirm our results.

Syncope is a common condition encountered in the emergency department (ED), accounting for about 0.6-3% of all ED visits. Despite its high frequency, a widely accepted management strategy for patients with syncope in the ED is still missing. Since syncope can be the presenting condition of many diseases, both severe and benign, most research efforts have focused on strategies to obtain a definitive etiologic diagnosis. Nevertheless, in everyday clinical practice, a definitive diagnosis is rarely reached after the first evaluation. It is thus troublesome to aid clinicians' reasoning by simply focusing on differential diagnoses. With the current review, we would like to propose a management strategy that guides clinicians both in the identification of conditions that warrant immediate treatment and in the management of patients for whom a diagnosis is not immediately reached, differentiating those that can be safely discharged from those that should be admitted to the hospital or monitored before a final decision. We propose the mnemonic acronym RED-SOS: Recognize syncope; Exclude life-threatening conditions; Diagnose; Stratify the risk of adverse events; Observe; decide on the Setting of care. Based on this acronym, in the different sections of the review, we discuss all the elements that clinicians should consider when assessing patients with syncope.

Background: Alpha-1 antitrypsin deficiency (AATD) can result in severe liver and respiratory disorders. The uninhibited elastase activity on the elastic tissue of arterial walls suggests that AATD may also impact vascular health. Thus, we performed a meta-analysis of the studies evaluating cardiovascular risk in individuals with AATD and non-AATD controls., Methods: A systematic literature search was conducted in the main scientific databases according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Differences between cases and controls were expressed as odds ratios (OR) with 95% confidence intervals (95%CI). The protocol was registered on PROSPERO under the identification number CRD42023429756., Results: The analysis of eight studies showed that, with a prevented fraction of disease of 15.0% and a corresponding OR of 0.779 (95%CI: 0.665-0.912; p = 0.002), a total of 24,428 individuals with AATD exhibited a significantly lower risk of ischemic heart disease compared to 534,654 non-AATD controls. Accordingly, given a prevented fraction of disease of 19.5%, a lower risk of acute myocardial infarction was documented when analyzing four studies on 21,741 cases and 513,733 controls (OR: 0.774; 95%CI: 0.599-0.999; p = 0.049). Sensitivity and subgroup analyses substantially confirmed results. Meta-regression models suggested that these findings were not influenced by AATD genotypes or prevalence of chronic obstructive pulmonary disease (COPD) among cases and controls, while higher differences in the prevalence of male sex (Z-score: 3.40; p < 0.001), hypertension (Z-score: 2.31; p = 0.021), and diabetes (Z-score: 4.25; p < 0.001) were associated with a lower effect size., Conclusions: Individuals with AATD may exhibit a reduced risk of ischemic heart disease, even in the presence of mild deficiency of the serine protease inhibitor. Although caution is warranted due to the observational nature of the data, future pharmacological and rehabilitation strategies should also take this controversial relationship into account.

Arterial hypertension (AH) is a major risk factor for the development of heart failure (HF) which represents one of the leading causes of mortality and morbidity worldwide. The chronic hemodynamic overload induced by AH is responsible for different types of functional and morphological adaptation of the cardiovascular system, defined as hypertensive mediated target organ damage (HMOD), whose identification is of fundamental importance for diagnostic and prognostic purposes. Among HMODs, left ventricular hypertrophy (LVH), coronary microvascular dysfunction (CMVD), and subclinical systolic dysfunction have been shown to play a role in the pathogenesis of HF and represent promising therapeutic targets. Furthermore, LVH represents a strong predictor of cardiovascular events in hypertensive patients, influencing per se the development of CMVD and systolic dysfunction. Clinical evidence suggests considering LVH as a diagnostic marker for HF with preserved ejection fraction (HFpEF). Several studies have also shown that microalbuminuria, a parameter of abnormal renal function, is implicated in the development of HFpEF and in predicting the prognosis of patients with HF. The present review highlights recent evidence on the main HMOD, focusing in particular on LVH, CMD, subclinical systolic dysfunction, and microalbuminuria leading to HFpEF.

Background: Diagnosis and treatment of hypertension emergency (HE) and urgency (HU) may vary according to the physicians involved and the setting of the treatment. The aim of this study was to investigate differences in management of HE and HU according to the work setting of the physicians. Methods: The young investigators of the Italian Society of Hypertension developed a 23-item questionnaire spread by email invitation to the members of Italian Scientific societies involved in the field of emergency medicine and hypertension. Results: Six-hundred and sixty-five questionnaires were collected. No differences emerged for the correct definitions of HE and HU or for the investigation of possible drugs that may be responsible for an acute increase in BP. The techniques used to assess BP values (p < 0.004) and the sizes of cuffs available were different according to the setting. Cardiologists more frequently defined epistaxis (55.2% p = 0.012) and conjunctival hemorrhages (70.7%, p < 0.0001) as possible presentation of HE, and rarely considered dyspnea (67.2% p = 0.014) or chest pain (72.4%, p = 0.001). Intensive care (IC) unit doctors were more familiar with lung ultrasound (50% p = 0.004). With regard to therapy, cardiologists reported the lowest prescription of i.v. labetalol (39.6%, p = 0.003) and the highest of s.l. nifedipine (43.1% p < 0.001). After discharge, almost all categories of physicians required home BP assessment or referral to a general practitioner, whereas hypertensive center evaluation or ambulatory BP monitoring were less frequently suggested. Conclusion: Management and treatment of HE and HU may be different according to the doctor’s specialty. Educational initiatives should be done to standardize treatment protocols and to improve medical knowledge.

Aortic stenosis (AS) is a very common valve disease and is associated with high mortality once it becomes symptomatic. Arterial hypertension (HT) has a high prevalence among patients with AS leading to worse left ventricle remodeling and faster degeneration of the valve. HT also interferes with the assessment of the severity of AS, leading to an underestimation of the real degree of stenosis. Treatment of HT in AS has not historically been pursued due to the fear of excess reduction in afterload without a possibility of increasing stroke volume due to the fixed aortic valve, but most recent evidence shows that several drugs are safe and effective in reducing BP in patients with HT and AS. RAAS inhibitors and beta-blockers provide benefit in selected populations based on their profile of pharmacokinetics and pharmacodynamics. Different drugs, on the other hand, have proved to be unsafe, such as calcium channel blockers, or simply not easy enough to handle to be recommended in clinical practice, such as PDE5i, MRA or sodium nitroprusside. The present review highlights all available studies on HT and AS to guide antihypertensive treatment.

The significant reduction in 'ischemic time' through capillary diffusion of primary percutaneous intervention (pPCI) has rendered myocardial-ischemia reperfusion injury (MIRI) prevention a major issue in order to improve the prognosis of ST elevation myocardial infarction (STEMI) patients. In fact, while the ischemic damage increases with the severity and the duration of blood flow reduction, reperfusion injury reaches its maximum with a moderate amount of ischemic injury. MIRI leads to the development of post-STEMI left ventricular remodeling (post-STEMI LVR), thereby increasing the risk of arrhythmias and heart failure. Single pharmacological and mechanical interventions have shown some benefits, but have not satisfactorily reduced mortality. Therefore, a multitarget therapeutic strategy is needed, but no univocal indications have come from the clinical trials performed so far. On the basis of the results of the consistent clinical studies analyzed in this review, we try to design a randomized clinical trial aimed at evaluating the effects of a reasoned multitarget therapeutic strategy on the prevention of post-STEMI LVR. In fact, we believe that the correct timing of pharmacological and mechanical intervention application, according to their specific ability to interfere with survival pathways, may significantly reduce the incidence of post-STEMI LVR and thus improve patient prognosis.

Lower myocardial mechanic-energetic efficiency (MEEi), expressed as stroke volume/heart rate ratio (SV/HR) in mL/s/g of the left ventricular (LV) mass, is associated with the incidence of heart failure in subjects with cardiometabolic disorders. We explored the association of MEEi with LV systolic circumferential and longitudinal myocardial function in 480 subjects with increased body mass index (BMI) without known cardiovascular disease (mean age 47 ± 9 years, 61% women, 63% obese, 74% with hypertension) participating in the fat-associated cardiovascular dysfunction (FATCOR) study. Insulin resistance was assessed by the homeostasis model assessment insulin-resistance index (HOMA-IR). SV was calculated by Doppler echocardiography. The LV systolic circumferential myocardial function was evaluated by midwall fractional shortening (MFS) and longitudinal function by global longitudinal strain (GLS). Patients were grouped into MEEi quartiles. The lowest MEEi quartile (<0.41 mL/s per g) was considered low MEEi. The association of MEEi with MFS and GLS were tested in multivariable linear regression analyses. Patients with low MEEi were more frequently men, with obesity and hypertension, dyslipidemia and higher HOMA-IR index (all p for trend <0.05). In multivariable analyses, lower MEEi was associated with lower LV myocardial function by MFS and GLS independent of higher LV mass and clinical variables, including older age, male sex, presence of hypertension and a higher triglycerides level (all p < 0.05). In conclusion, in subjects with increased BMI without known cardiovascular disease participating in the FATCOR study, reduced MEEi was associated with lower LV myocardial function both in the circumferential and longitudinal direction, independent of cardiometabolic factors.

Background: Cardio-vascular target organ damage predicts the onset of type 2 diabetes mellitus (DM) in hypertensive patients. Whether an increased incidence of DM is also in relation to the severity of coronary atherosclerosis is unknown., Objective: We evaluated the onset of DM in relation to the extent and severity of coronary atherosclerosis, using the SYNTAX (Synergy between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery) score (SS), in patients with stable angina or acute coronary syndromes, referred for coronary angiography (CA)., Methods: Non-diabetic patients that underwent CA for the first time were included, and the SS was computed. Predictors of DM onset in low, medium, and high SSs were investigated., Results: Five hundred and seventy patients were included, and the mean SS was 6.3 ± 7.6. During a median follow-up of 79 months (interquartile range (IQR): 67-94), 74 patients (13%) developed DM. The risk of DM onset was significantly higher in the patients with a medium or high SS (hazard ratio (HR)-95% confidence interval (CI): 16 (4-61), p < 0.0001; and 30 (9-105), p < 0.0001, vs low SS, respectively), even after adjustment for obesity, history of hypertension, impaired fasting glucose, and cardiovascular therapy., Conclusions: The severity and extent of the coronary atherosclerosis, evaluated by the SS, is a strong and independent predictor of the development of DM in patients, referred to CA.

An estimation of myocardial mechano-energetic efficiency (MEE) per unit of left ventricular (LV) mass (MEEi) can significantly predict composite cardiovascular (CV) events in treated hypertensive patients with normal ejection fraction (EF), after adjustment for LV hypertrophy (LVH). We have tested whether MEEi predicts incident heart failure (HF), after adjustment for LVH, in the population-based cohort of a "Strong Heart Study" (SHS) with normal EF. We included 1,912 SHS participants (age 59 ± 8 years; 64% women) with preserved EF (≥50%) and without prevalent CV disease. MEE was estimated as the ratio of stroke work to the "double product" of heart rate times systolic blood pressure. MEEi was calculated as MEE/LV mass, and analyzed in quartiles. During a follow-up study of 9.2 ± 2.3 years, 126 participants developed HF (7%). HF was preceded by acute myocardial infarction (AMI) in 94 participants. A Kaplan-Meier plot, in quartiles of MEEi, demonstrated significant differences, substantially due to the deviation of the lowest quartile ( p < 0.0001). Using AMI as a competing risk event, sequential models of Cox regression for incident HF (including significant confounders), demonstrated that low MEEi predicted incident HF not due to AMI ( p = 0.026), after adjustment for significant effect of age, LVH, prolonged LV relaxation, diabetes, and smoking habits with negligible effects for sex, hypertension, antihypertensive therapy, obesity, and hyperlipemia. Low LV mechano-energetic efficiency per unit of LVM, is a predictor of incident, non-AMI related, HF in subjects with initially normal EF., Competing Interests: The authors declare no conflict of interest.