Objective: The maternal vasculature undergoes significant adaptations during pregnancy to meet the increased metabolic demands of the developing fetus. These adaptations include increased cardiac output and blood volume, as well as reduced systemic vascular resistance to support the fetoplacental unit. In Hypertensive disorders of pregnancy (HDP) there is an impaired cardiovascular adaptation to pregnancy with effects extending beyond the duration of the pregnancy. In the present study we aimed to characterize long-term cardiovascular status of women who suffered from HDP. Design and method: Fifty-eight women who attended at least one post-partum visit in our HDP Clinic (IRCCS Policlinico Sant’Orsola-Malpighi, Bologna, Italy) and a follow-up visit after at least 5 years from delivery were enrolled in the study. Exclusion criteria included multiple pregnancy, fetal genetic or congenital abnormalities, maternal history of organ transplantation or chronic kidney disease (CKD), and absence of a post-partum echocardiographic evaluation. In the follow-up visit participants underwent a complete cardiovascular assessment including echocardiography and multiparametric vascular function assessment. Results: Two major cardiovascular events occurred, one stroke and one myocardial infarction, both in women with index-pregnancy complicated by preeclampsia (PE). While not statistically significant, women with HDP-non-PE and PE displayed a trend towards an increased risk of developing composite cardiovascular outcome, and women with PE tended to experience it sooner (Figure 1). Nearly half of the women with a history of HDP, whether PE or HDP-non-PE, developed chronic hypertension. Some women also developed hyperuricemia, CKD, and type 2 diabetes at follow-up, most of them with a previous history of PE. Structural and functional cardiac changes were observed in a few cases, especially among women with PE, and vascular dysfunction was more common in women with a history of HDP compared to those with normotensive pregnancies (Figure 2). Conclusions: Results of the present study adds on literature on long-term cardiovascular impact of HDP and further emphasize the importance of a timely follow-up of women who suffered from HDP and particularly PE.

Background: Serum uric acid (SUA) is a known biomarker of severity in acute heart failure (AHF), reflecting the intricate interplay between cardiovascular and metabolic dysfunction. Since SUA can increase in response to worsening kidney function, and subjects with AHF often have cardiorenal syndrome or are on diuretic therapy, we tested whether the ratio of SUA to eGFR might provide prognostic value in elderly hospitalized for AHF. Methods: The BOTERO-AHF Study (BOlogna study of Therapies, Epidemiology and Radiodiagnostic Outcomes in Acute Heart Failure patients) included 293 patients admitted for AHF who were consecutively enrolled from January 2020 onwards. We compared the baseline characteristics of participants who had a composite outcome (CO) ( n = 203) of death or re-hospitalization for AHF within 12 months from discharge to those without CO ( n = 90), and we assessed the prognostic impact of SUA/eGFR for 12-months CO. Results: SUA/eGFR was significantly higher in participants who experienced a CO within 12 months from discharge for AHF, compared to those who did not experience any CO (17.8 (16.6) vs. 13.7 (12.1) mg/dl/ml/ min*100, p = 0.008). SUA/eGFR, and not SUA alone, was associated with an increase in the rate of CO (unadjusted HR 1.011, CI 95% 1.004 -1.019, p = 0.003). This association lost significance in participants under treatment with xanthine oxidase inhibitors but remained significant after adjustment for multiple confounders. Conclusion: The SUA/ eGFR ratio provides prognostic value in elderly patients hospitalized for AHF. Future studies may clarify if SUA/eGFR and XOI may represent novel diagnostic and therapeutic approaches for subgroups of patients with AHF.

Background and aimsFast-track care have been proved to reduce the short-term risk of stroke after transient ischemic attack (TIA). We aimed to investigate stroke risk and to characterize short- and long-term stroke predictors in a large cohort of TIA patients undergoing fast-track management.MethodsProspective study, enrolling consecutive TIA patients admitted to a Northern Italy emergency department from August 2010 to December 2017. All patients underwent fast-track care within 24 h of admission. The primary outcome was defined as the first stroke recurrence at 90 days, 12 and 60 months after TIA. Stroke incidence with 95% confidence interval (CI) at each timepoint was calculated using Poisson regression. Predictors of stroke recurrence were evaluated with Cox regression analysis. The number needed to treat (NNT) of fast-track care in preventing 90-day stroke recurrence in respect to the estimates based on baseline ABCD2 score was also calculated.ResultsWe enrolled 1,035 patients (54.2% males). Stroke incidence was low throughout the follow-up with rates of 2.2% [95% CI 1.4–3.3%] at 90 days, 2.9% [95% CI 1.9–4.2%] at 12 months and 7.1% [95% CI 5.4–9.0%] at 60 months. Multiple TIA, speech disturbances and presence of ischemic lesion at neuroimaging predicted stroke recurrence at each timepoint. Male sex and increasing age predicted 90-day and 60-month stroke risk, respectively. Hypertension was associated with higher 12-month and 60-month stroke risk. No specific TIA etiology predicted higher stroke risk throughout the follow-up. The NNT for fast-track care in preventing 90-day stroke was 14.5 [95% CI 11.3–20.4] in the overall cohort and 6.8 [95% CI 4.6–13.5] in patients with baseline ABCD2 of 6 to 7.ConclusionOur findings support the effectiveness of fast-track care in preventing both short- and long-term stroke recurrence after TIA. Particular effort should be made to identify and monitor patients with baseline predictors of higher stroke risk, which may vary according to follow-up duration.

The prevalence of hypertensive disorders of pregnancy (HDP) steadily increased in past years partly because of advanced maternal age and partly because of ever-wider access to assisted reproduction techniques in women with pre-existing complex medical conditions [ [1] Umesawa M. Kobashi G. Epidemiology of hypertensive disorders in pregnancy: prevalence, risk factors, predictors and prognosis. Hypertens Res. 2017; 40: 213-220 Crossref PubMed Scopus (277) Google Scholar ]. Preeclampsia (PE), the most severe type of hypertensive disorder of pregnancy (HDP), is the leading cause of maternal and perinatal morbidity and mortality. PE is a pregnancy-associated syndrome involving multiple organs with long-term health implications for both mothers and their offspring [ [2] Bokslag A. van Weissenbruch M. Mol B.W. de Groot C.J. Preeclampsia; short and long-term consequences for mother and neonate. Early Hum Dev. 2016; 102: 47-50 Crossref PubMed Scopus (254) Google Scholar ]. PE increases the risk for future cardiovascular and renal diseases and, in turn, women already affected by these diseases before conception are at increased risk of developing PE [ [3] Paauw N.D. Luijken K. Franx A. Verhaar M.C. Lely A.T. Long-term renal and cardiovascular risk after preeclampsia: towards screening and prevention. Clin Sci (Lond). 2016; 130: 239-246 Crossref PubMed Scopus (63) Google Scholar ]. For these reasons PE is not considered anymore a solely pregnancy disease, representing a topic of sub-specialization for internists, particularly those specialized in hypertension [ [4] Tranquilli A.L. Landi B. Giannubilo S.R. Sibai B.M. Preeclampsia: no longer solely a pregnancy disease. Pregnancy Hypertens. 2012; 2: 350-357 Crossref PubMed Scopus (44) Google Scholar ]. Although the sub-specialization of obstetric medicine has been recently recognized as a useful intersection between the disciplines of Internal Medicine and Obstetrics, the role of internists in the multidisciplinary team involved in the care of women at high-risk of developing PE has not yet been established [ [5] Pourrat O. Obstetric medicine: a key role for the internist. Eur J Intern Med. 2005; 16: 220 Abstract Full Text Full Text PDF PubMed Scopus (5) Google Scholar ]. Here we describe the results of our study aimed at assessing the associations between prenatal care by internists specialized in hypertension and pregnancy outcomes of a high-risk population.

Objective:Preeclampsia is one of the most severe diseases among the hypertensive disorders of pregnancy (HDP) and the leading cause of maternal and fetal morbidity and mortality. It is of crucial importance to early identify women at a high risk for preeclampsia to implement appropriate preventive strategies. In our study, we aimed to test the hypothesis that serum uric acid to creatinine ratio (SUA/sCr) is related to the development of preeclampsia and maternal and neonatal complications.Methods:We searched for uric acid and creatine values in the medical records of 269 women who consecutively attended our HDP Clinic from December 2018 to December 2022. We compared the baseline characteristics of participants with normotensive pregnancy (n = 57), to those with HDP without preeclampsia (HDP-non-PE) (n = 100) and those with preeclampsia (n = 112), and we performed adjusted logistic regression analysis to test the associations between SUA/sCr and the development of preeclampsia and maternal and neonatal complications.Results:SUA/sCr was consistently higher in women with preeclampsia in all trimesters of pregnancy. Higher SUA/sCr at the third trimester was associated with an increased odd of developing preeclampsia [odds ratio (OR) 1.29, confidence interval (CI) 1.15-1.50, P = 0.001], preterm birth (OR 1.23, CI 1.05-1.45, P = 0.011), and composite neonatal outcome (OR 1.33, CI 1.12-1.59, P = 0.001), after adjustment for age, BMI before pregnancy, nulliparity, antihypertensive therapy, and acetylsalicylic acid therapy during pregnancy.Conclusions:Having higher SUA/sCr during pregnancy is associated with the development of PE and adverse pregnancy outcomes. Controlled prospective studies are warranted to clarify the predictive power of this novel marker during pregnancy.

Our aim was to evaluate if a nutritional intervention with a dietary supplement (Diuripres®) containing magnesium, standardized extract of orthosiphon, hawthorn, and hibiscus could positively affect blood pressure (BP), vascular health, and metabolic parameters in 60 individuals with high‐normal BP or stage I hypertension. Participants followed a low‐fat low‐sodium Mediterranean diet for 4 weeks before being randomly allocated to 8‐week treatment with two pills each day of either Diuripres® or placebo. Diuripres® significantly decreased systolic BP compared to placebo after 4 weeks (3.1 ± 0.8 mmHg; p < 0.05) and more consistently after 8 weeks (3.4 ± 0.9 mmHg; p < 0.05). At 8‐week follow‐up, after correction for multiple testing, dietary supplementation with Diuripres® was associated with significant improvements in diastolic BP (−3.1 ± 0.6 mmHg; p < 0.05), aortic BP (−4.3 ± 0.4 mmHg; p < 0.05), and high‐sensitivity C‐reactive protein (hs‐CRP; 0.04 ± 0.01 mg/dL; p < 0.05) in comparison with baseline. The reductions in diastolic BP (−‐3.8 ± 0.7 mmHg; p < 0.05), aortic BP (−5.2 ± 1.0 mmHg; p < 0.05), and hs‐CRP (−0.03 ± 0.01 mg/dL; p < 0.05) were also significant compared to placebo. Therefore, our study shows that dietary supplementation with Diuripres® may be useful in individuals with high‐normal BP or stage I hypertension.

Objective: Preeclampsia (PE) is the leading cause of maternal and fetal morbidity and mortality. PE presents with new-onset hypertension after 20 weeks of gestation that can progress rapidly leading to serious complications for both the mother and the fetus. Thus, it is of crucial importance early identifying women at high-risk for PE as early as during the first trimester of pregnancy, to implement the appropriate management and therapeutic strategies. In our study we aimed to assess the associations between serum uric acid to creatinine ratio (SUA/Cr), the development of PE and PE-related maternal and neonatal complications. Design and method: We searched for uric acid and creatine values in the medical records of 269 pregnant women who attended our Hypertensive Disorders in Pregnancy Clinic from December 2015 to December 2021. Two-hundreds and twelve women developed hypertensive disorders of pregnancy (HDP) and 57 had normotensive pregnancies. Of the 201 women with HDP, 112 were diagnosed with PE. After comparing baseline characteristics of the enrolled women, we performed logistic regression analysis models to assess the associations between SUA/Cr, development of PE, and PE-related maternal and neonatal complications. Results: Women who developed PE were more frequently nulliparous and had a higher rate of preterm delivery and maternal and neonatal complications, compared to women with HDP and healthy controls. Serum SUA/Cr was consistently higher in women with PE in all trimesters of pregnancy. Serum uric acid and creatinine alone were higher only during the third trimester in women with PE compared to women with HDP and healthy controls. Third trimester SUA/Cr was associated with an increased risk of developing PE (OR 1.29, CI 1.15 - 1.50, p = 0.001), of preterm birth (OR 1.23, CI 1.05 - 1.45, p = 0.011), and of a composite neonatal outcome (OR 1.33, CI 1.12 - 1.59, p = 0.001), after adjustment for age, BMI before pregnancy, nulliparity, hypertensive therapy, and acetylsalicylic acid therapy during pregnancy. Conclusions: In our study, women who develop PE had elevated SUA/Cr throughout all the trimesters. SUA/Cr at the third trimester of pregnancy was associated with an increased risk of PE development and neonatal complications.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are effective and safe lipid-lowering treatments (LLT). The primary endpoint of the study was to assess the prevalence of patients eligible for treatment with PCSK9 inhibitors in a real-life clinical setting in Italy before and after the recent enlargement of reimbursement criteria. For this study, we consecutively considered the clinical record forms of 6231 outpatients consecutively admitted at the Lipid Clinic of the University Hospital of Bologna (Italy). Patients were stratified according to whether they were allowed or not allowed to access to treatment with PCSK9 inhibitors based on national prescription criteria and reimbursement rules issued by the Italian Medicines Agency (AIFA). According to the indications of the European Medicines Agency (EMA), 986 patients were candidates to treatment with PCSK9 inhibitors. However, following the prescription criteria issued by AIFA, only 180 patients were allowed to access to PCSK9 inhibitors before reimbursement criteria enlargement while 322 (+14.4%) with the current ones. Based on our observations, low-cost tailored therapeutic interventions for individual patients can significantly reduce the number of patients potentially needing treatment with PCSK9 inhibitors among those who are not allowed to access to the treatment. The application of enlarged reimbursement criteria for PCSK9 inhibitors could mildly improve possibility to adequately manage high-risk hypercholesterolemic subjects in the setting of an outpatient lipid clinic.

AIMS:We investigated sex and racial inequalities in clinical trials testing serum uric acid (SUA) lowering drugs and analyzed the temporal trends of participation among the pre-specified demographic groups. Data were collected from publications of clinical trials testing SUA-lowering drugs. Linear regression analysis was performed to assess the relation between drug approval year and proportion of women and minorities enrolled in clinical studies. DATA SYNTHESIS:The mean percentage enrollment of women in clinical trials significantly decreased over the time (r = -0.43, P-value = 0.02). Moreover, there was a statistically significant difference in mean percentage enrollment of women among trials testing different SUA-lowering drugs, with the highest representation in rasburicase (71.1%) and the lowest representation of women in dotinurad (0.8%). Over the time, also the mean percentage enrollment of racial minorities decreased, passing from 8.7% to 2.2% in a 10-year period. Women were proportionally underrepresented compared with their share of the population with asymptomatic hyperuricemia, overall (participation-to-prevalence ratio (PPR) = 0.34), in trials testing xanthine oxiase inhibitors (PPR = 0.38) and uricosurics (PPR = 0.29), and in trials with febuxostat, allopurinol, pegloticase, halofenate/arhalofenate, verinurad, lesinurad and dotinurad. Women were proportionally underreppresented also compared with their share of the population with gout, overall (PPR = 0.69) and in trials testing XOIs (PPR = 0.69), uricosurics (PPR = 0.68), and all SUA-lowering drugs excepted for rasburicase, pegloticase and topiroxostat. CONCLUSIONS:Our analysis shows that women and racial and ethnical minorities are underrepresented in controlled clinical trials testing SUA-lowering drugs, with similar pattern across drug classes.

AIM:To evaluated echocardiographic aspects in women with history of preeclampsia or preeclampsia-related complications in their previous pregnancies. MATERIALS AND METHODS:Consecutive women receiving echocardiography during daily clinical echolab activity were studied using complete echocardiographic examination data and anamnestic data collection of hypertension, diabetes, dyslipidemia, and rheumatic diseases. Studied women should have at least one pregnancy in more than the 10 past years, and were subdivided into two groups according to the history of complicated or physiological pregnancy. Complicated pregnancies were defined by preeclampsia or preeclampsia-related complication, such as preterm delivery or small-for-gestational age newborn. Echocardiographic parameters and prevalence of hypertension, diabetes, dyslipidemia, and rheumatic disease were compared between the two groups of studied women. RESULTS:From March 2016 to May 2020, 545 women were studied, of whom 218 had a history of complicated pregnancy (mean age 60.81 ± 11.109 years vs. 62.78 ± 9.758 years of not complicated pregnancy; P = 0.03). Compared with physiological pregnancy women, complicated pregnancy ones were shorter (159.97 ± 6.608 vs. 161.42 ± 6.427 cm; P = 0.012) with lower body surface area (1.678 ± 0.1937 vs. 1.715 ± 0.1662 m2; P = 0.02), had higher prevalence of diabetes (6.9 vs. 3.1%; P = 0.04; odds ratio = 2.34; CI 1.0323--5.3148) and rheumatic diseases (33 vs. 22.3%; P = 0.006; odds ratio = 1.72; CI 1.1688--2.5191), and showed a slight, not significant higher prevalence of hypertension. As for echocardiographic parameters, they showed significantly higher values of end-diastolic left ventricular posterior wall (LPWd) (P = 0.034), a trend toward a more concentric geometry, and a worse longitudinal systolic left and right ventricle performance, represented by lower tissue Doppler systolic waves (septal: 7.41 ± 1.255 vs. 7.69 ± 1.376 cm/s; P = 0.018; and tricuspidalic: 12.64 ± 2.377 vs. 13.32 ± 2.548 cm/s; P = 0.003). CONCLUSION:Patients with previous preeclampsia present an increased risk of hypertension, diabetes, and rheumatic diseases, suggesting that these women could share a specific predisposition to a high-risk profile. Furthermore, they show a higher prevalence of classically considered echocardiographic hypertensive-derived cardiac damage, suggesting structural and functional left ventricular modifications as subclinical aspects of long-term worse cardiovascular prognosis for these women.

Left atrial enlargement (LAe) is a subclinical marker of hypertensive-mediated organ damage, which is important to identify in cardiovascular risk stratification. Recently, LA indexing for height was suggested as a more accurate marker of defining LAe. Our aim was to test the difference in LAe prevalence using body surface area (BSA) and height 2 definitions in an essential hypertensive population. A total of 441 essential hypertensive patients underwent complete clinical and echocardiographic evaluation. Left atrial volume (LAV), left ventricular morphology, and systolic-diastolic function were evaluated. LAe was twice as prevalent when defined using height 2 (LAe h2 ) indexation rather than BSA (LAe BSA ) (51% vs. 23%, p < 0.001). LAe h2 , but not LAe BSA , was more prevalent in females ( p < 0.001). Males and females also differed in left ventricular hypertrophy ( p = 0.046) and left ventricular diastolic dysfunction (LVDD) indexes (septal Em/Etdi: p = 0.009; lateral Em/Etdi: p = 0.003; mean Em/Etdi: p < 0.002). All patients presenting LAe BSA also met the criteria for LAe h2 . According to the presence/absence of LAe, we created three groups (Norm = BSA−/h 2 -; DilH = BSA−/h 2 +; DilHB = BSA+/h 2 +). The female sex prevalence in the DilH group was higher than that in the other two groups (Norm: p < 0.001; DilHB: p = 0.036). LVH and mean and septal Em/Etdi increased from the Norm to the DilH group and from the DilH to the DilHB group ( p < 0.05 for all comparisons). These results show that LAe h2 identified twice as many patients as comparing LAe to LAe BSA , but that both LAe h2 and LAe BSA definitions were associated with LVH and LVDD. In female patients, the LAe h2 definition and its sex-specific threshold seem to be more sensitive than LAe BSA in identifying chamber enlargement.

Objectives To evaluate the frequency, clinical and etiologic features, and short- and long-term outcomes of early recurrent TIA. Methods This prospective observational cohort study enrolled all consecutive patients with TIA referred to our emergency department and diagnosed by a vascular neurologist. Expedited assessment and best secondary prevention were performed within 24 hours. Primary endpoints were stroke and a composite outcome including stroke, acute coronary syndrome, and vascular death at 3, 12, and, for a subset of patients, 60 months; secondary outcomes were TIA relapse, cerebral hemorrhage, new-onset atrial fibrillation, and death resulting from other causes. Concordance between index TIA and subsequent stroke etiologies was also evaluated. Results A total of 1,035 patients (822 with a single TIA, 213 with recurrent TIA = 21%) were enrolled from August 2010 to December 2017. Capsular warning syndrome and large artery atherosclerosis showed the strongest relationship with early recurrent TIA. The risk of stroke was significantly higher in the early recurrent TIA subgroup at each follow-up, and most stroke episodes occurred within 48 hours of index TIA. TIAs with lesion, dysarthria, and leukoaraiosis were the 3- and 12-month independent predictors of stroke incidence after early recurrent TIA subgroup. Index TIA and subsequent stroke etiologies showed substantial concordance. An ABCD3 score >6 predicted a higher risk of stroke recurrence over the entire follow-up. Conclusions Our study evaluated long-term outcome after early recurrent TIA. Our observations support the importance of promptly detecting and treating patients with early recurrent TIAs to reduce the high early and long-term risk of poor clinical outcomes.

Objectives To evaluate the frequency, clinical and etiologic features, and short- and long-term outcomes of early recurrent TIA. Methods This prospective observational cohort study enrolled all consecutive patients with TIA referred to our emergency department and diagnosed by a vascular neurologist. Expedited assessment and best secondary prevention were performed within 24 hours. Primary endpoints were stroke and a composite outcome including stroke, acute coronary syndrome, and vascular death at 3, 12, and, for a subset of patients, 60 months; secondary outcomes were TIA relapse, cerebral hemorrhage, new-onset atrial fibrillation, and death resulting from other causes. Concordance between index TIA and subsequent stroke etiologies was also evaluated. Results A total of 1,035 patients (822 with a single TIA, 213 with recurrent TIA = 21%) were enrolled from August 2010 to December 2017. Capsular warning syndrome and large artery atherosclerosis showed the strongest relationship with early recurrent TIA. The risk of stroke was significantly higher in the early recurrent TIA subgroup at each follow-up, and most stroke episodes occurred within 48 hours of index TIA. TIAs with lesion, dysarthria, and leukoaraiosis were the 3- and 12-month independent predictors of stroke incidence after early recurrent TIA subgroup. Index TIA and subsequent stroke etiologies showed substantial concordance. An ABCD(3)score >6 predicted a higher risk of stroke recurrence over the entire follow-up. Conclusions Our study evaluated long-term outcome after early recurrent TIA. Our observations support the importance of promptly detecting and treating patients with early recurrent TIAs to reduce the high early and long-term risk of poor clinical outcomes.

Aim: Sacubitril valsartan (SV) has revolutionized disease history in patients with heart failure and reduced ejection fraction (HFrEF). Our study assessed SV impact on clinical and echocardiographic parameters in HFrEF outpatients previously treated with optimized therapy. Methods: Forty-nine HFrEF outpatients were retrospectively included in the study. We collected data from transthoracic echocardiography and clinical assessment at baseline and after 3 +/- 1 and 12 +/- 1 months of treatment with SV. Results were also stratified by sex to analyse possible sex-based differences in reverse remodelling response to SV. Results: After 3 months of treatment we observed a significative improvement of both systolic and diastolic function with a reduction of left ventricular mass and relative wall thickness (RWT). At 12 months we observed a further improvement of all previous parameters, plus systolic pulmonary artery pressure (PAP) and left atrial (LA) diameter. In women, most of the echocardiographic parameters improved after SV initiation, but did not reach the statistical significance, except for left ventricular ejection fraction (LVEF), PAP and LA diameter. As for clinical parameters, SV improved New York Heart Association (NYHA) Class, systolic blood pressure and loop diuretic dosage with a mild but significative increase in serum creatinine and potassium. Conclusion: Our study showed significative reverse remodelling properties of SV with an improvement of LV volumes, mass and systo-diastolic function. NYHA Class, systolic blood pressure and loop diuretic dosage also improved with only mild increase in serum creatinine and potassium. Women showed a lesser extent of reverse remodelling compared with men. (C) 2020 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Background Chronic obstructive pulmonary disease (COPD) and heart failure (HF) often coexist. Moreover, elderly patients suffering from HF have a higher incidence of COPD, which further complicates their clinical condition. Indacaterol/glycopirronium has shown benefits in the treatment of COPD, with few cardiologic adverse effects. We evaluated the safety and efficacy of this therapy in patients with history of HF. Methods We enrolled 56 patients with a history of HF (New York Heart Association [NYHA] classes II and III) and stable COPD. We evaluated blood samples, clinical assessment, echocardiograms and basal spirometry at baseline and after 6 months of therapy with indacaterol/glycopirronium. In addition, the number of re-hospitalizations during the treatment period was evaluated. Results The treatment was well tolerated. Brain natriuretic peptide (BNP) levels were significantly reduced compared with baseline ( p < 0.001) after 6 months of treatment, and a higher percentage of patients improved their clinical status compared with baseline ( p < 0.001). Minor changes were noted in the hemodynamic and metabolic parameters. Significant improvements in the echocardiographic parameters were noted in HF with reduced ejection fraction (HFrEF) patients. All respiratory parameters (forced expiratory volume in 1 s [FEV1], FEV1/forced vital capacity [FVC] ratio and COPD Assessment Test [CAT] scores) improved significantly ( p < 0.001). No hospitalizations owing to HF or COPD exacerbation occurred. One patient died of respiratory failure. Conclusion Indacaterol/glycopirronium was well-tolerated and effective in the treatment of COPD in this cohort of patients with a history of HF. Further studies are needed to clarify whether this compound can have a direct role in improving overall cardiovascular function.

Hyperuricemia is an emerging risk factor for the development of heart failure (HF) and is associated with a worsen prognosis of the disease. The effect of urate lowering drugs (ULT) and, in particular, the xanthine oxidase inhibitor in patients with HF is controversial. The aim of the study is to compare the effects of treatment with two different xanthine oxidase inhibitors (allopurinol or febuxostat) on cardiovascular mortality in elderly patients with chronic HF in a setting of clinical practice. In this observational trial, 255 elderly patients affected by chronic HF and treated with ULT on top of optimal medical treatment for HF. The sample included only outpatients with mild-to-moderate HF mainly secondary to chronic arterial hypertension or coronary artery disease and not previously hospitalized for HF. Patient treated with febuxostat (N. 120) and allopurinol (N. 135) were balanced for most of the baseline variables. In particular age, NYHA class distribution, drug treatment and renal function were comparable at the baseline and during the observation in both groups (p > 0.05). After a mean follow-up period of 5.1 years, the cumulative cardiovascular survival was 0.96 (95% CI 0.93–0.99) in febuxostat-treated patients and 0.89 (95% CI 0.84–0.93) in those treated with allopurinol. The between group difference, adjusted for the main confounding risk factors, was statistically significant (p = 0.04). Our study results suggest that possibility that febuxostat, a selective XO inhibitor, may favorably affect cardiovascular mortality in comparison with allopurinol in elderly patients with mild-to-moderate HF. This preliminary observation deserves further evaluation in the next future.