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Background: Sacubitril/valsartan, the first agent to be approved in a new class of drugs called angiotensin receptor neprilysin inhibitors (ARNIs), has been shown to reduce cardiovascular mortality and morbidity compared to enalapril in outpatient subjects with chronic heart failure (HF) and reduced left ventricular ejection fraction (HFrEF). However, there is little real-world evidence about the efficacy of ARNIs in elderly hypertensive patients with HFrEF and comorbidities. Methods: In this prospective open-label study, 108 subjects, 54 of them (mean age 78.6 ± 8.2 years, 75.0 % male), with HFrEF (29.8 ± 4.3 %) and New York Heart Association (NYHA) class II-III symptoms were assigned to receive ARNIs twice daily, according to the recommended dosage of 24/26, 49/51, 97/103 mg. Patients were gender- and age-matched with a control arm of patients with HFrEF receiving the optimal standard therapy for HF. The clinic blood pressure (BP), N-terminal pro-B-type natriuretic peptide (NT-proBNP), estimated glomerular filtration rate (eGFR), blood glucose and glycated hemoglobin (HbA1c), uric acid (UA), left ventricular ejection fraction (LVEF) and NYHA class were evaluated at a mean follow-up of 12 months. During the follow-up, the clinical outcomes, including mortality and re-hospitalization for HF, were collected. Results: NYHA class significantly improved in the ARNI arm compared to the control (24.9 vs. 6.4 %, shifting from class III to II, and 55.4 vs. 25.2 %, from class II to I, p

Background The optimal long-term strategy for preventing recurrent venous thromboembolism (VTE) in patients with deep-vein thrombosis (DVT) is uncertain. Methods In 620 consecutive outpatients with a first proximal DVT who had completed at least three months of anticoagulation (unprovoked in 483, associated with minor risk factors in 137), the ultrasound presence of residual vein thrombosis (RVT) was assessed and defined as an incompressibility of at least 4 mm. In 517 patients without RVT and with negative D-dimer, anticoagulation was stopped and D-dimer was repeated after one and three months. Anticoagulation was resumed in 63 of the 72 patients in whom D-dimer reverted to positivity. Results During a mean follow-up of three years, recurrent VTE developed in 40 (7.7%) of the 517 patients, leading to an annual rate of 3.6% (95% CI, 2.6 to 4.9): 4.1% (95% CI, 2.9 to 5.7) in individuals with unprovoked DVT, and 2.2% (95% CI, 1.1 to 4.5) in those with DVT associated with minor risk factors. Of the 233 males with unprovoked DVT, 17 (7.3%) developed events in the first year of follow-up. Major bleeding complications occurred in 8 patients while on anticoagulation, leading to an annual rate of 1.2% (95% CI, 0.6 to 2.4). Conclusions Discontinuing anticoagulation in patients with a first episode of proximal DVT based on the assessment of RVT and serial D-dimer leads to an overall annual rate of recurrent VTE lower than 5.0%, which is the rate deemed as acceptable by the Subcommittee on Control of Anticoagulation of the ISTH. However, in males with unprovoked DVT there is room for further improving the long-term strategy of VTE prevention. ( ClinicalTrials.gov number, NCT01285661 ).

Although the role of homocysteinemia (Hcy) as a coronary risk factor (RF) has been scaled down, hyper-Hcy and carotid vascular damage (CVD) are still considered as RFs for cerebrovascular events. In 276 grade-1 hypertensives (160 men and 116 women aged 59.6 ± 15.0 years) without known cardiovascular disease and having hyper-Hcy (≥15 μM/L), subclinical CVD was evaluated by ultrasonographic carotid-wall intima media thickness (IMT). Hcy was divided into quartiles and C667→T polymorphism codifying for methylenetetrahydrofolate reductase (MTHFR) was determined. According to the genotype, subjects were divided into CC (wild), CT (heterozygote) and TT (homozygous mutation). Differences between continuous variables were evaluated by analysis of variance, while gender specific odds ratio (OR) and 95 % confidence intervals (CI) of CVD (IMT0.9 mm or plaque) were calculated by multivariate logistic regression analysis. Blood pressure (BP) values were not different across the quartiles of Hcy. In 46.4 % of cases, sub-clinical CVD was found, with a prevalence increasingly distributed in the quartiles of Hcy (31.9, 42, 52.2, 59.4 %, p0.001). Prevalence of TT allele of the MTHFR genotype was also significantly distributed in the quartiles of Hcy (13.6, 12.3, 23.5 and 50.6 %, p0.0001), whereas no relationship was found between genotype and CVD. The last quartile of Hcy predicted CVD (OR 1.32, CI 1.12-2.2, p = 0.02) independent of age (OR 1.23, CI 1.002-1.56, p = 0.0001), systolic BP (OR 1.52, CI 1.24-2.10), diabetes (OR 2.11, CI 1:32-2.88, p = 0.01) and smoking (OR 1.45, CI 1.14-1.98, p = 0.04). Adding gender did not modify the model. In hypertensives, Hcy values36.5 μM/L independently predict CVD and in those who are also diabetic and smokers, Hcy assessment without MTHFR genotype should be recommended to obtain a better stratification of global cerebrovascular risk.

The impact of residual pulmonary obstruction on the outcome of patients with pulmonary embolism is uncertain.We recruited 647 consecutive symptomatic patients with a first episode of pulmonary embolism, with or without concomitant deep venous thrombosis. They received conventional anticoagulation, were assessed for residual pulmonary obstruction through perfusion lung scanning after 6 months and then were followed up for up to 3 years. Recurrent venous thromboembolism and chronic thromboembolic pulmonary hypertension were assessed according to widely accepted criteria.Residual pulmonary obstruction was detected in 324 patients (50.1%, 95% CI 46.2–54.0%). Patients with residual pulmonary obstruction were more likely to be older and to have an unprovoked episode. After a 3-year follow-up, recurrent venous thromboembolism and/or chronic thromboembolic pulmonary hypertension developed in 34 out of the 324 patients (10.5%) with residual pulmonary obstruction and in 15 out of the 323 patients (4.6%) without residual pulmonary obstruction, leading to an adjusted hazard ratio of 2.26 (95% CI 1.23–4.16).Residual pulmonary obstruction, as detected with perfusion lung scanning at 6 months after a first episode of pulmonary embolism, is an independent predictor of recurrent venous thromboembolism and/or chronic thromboembolic pulmonary hypertension.

Arterial hypertension (HT) is age dependent and, with the prolongation of life expectancy, affects more and more elderly people. In the elderly, HT is a risk factor for organ damage and cardiovascular (CV) events. Both pharmacologic and nonpharmacologic reduction of blood pressure (BP) is associated with a corresponding decrease in systolic-diastolic or isolated systolic HT. Clinical trials have shown that BP lowering is associated with a decrease in stroke and other CV events. Therefore, BP reductionper seappears more important than a particular class of antihypertensive drugs. The benefit of antihypertensive treatment has been confirmed up to the age of 80 years, remaining unclear in the octogenarians. The benefit in lowering diastolic BP between 80 and 90 mmHg is well established, while that of lowering systolic BP below 140 mmHg requires further confirmations.

BACKGROUND The optimal duration of oral anticoagulant therapy in patients with deep venous thrombosis (DVT) of the lower extremities remains uncertain. OBJECTIVE To assess whether tailoring the duration of anticoagulation on the basis of the persistence of residual thrombi on ultrasonography reduces the rate of recurrent venous thromboembolism (VTE) compared with the administration of conventional fixed-duration treatment in adults with proximal DVT. DESIGN Parallel, randomized trial from 1999 to 2006. Trained physicians who assessed outcomes were blinded to patient assignment status, but patients and providers were not. SETTING 9 university or hospital centers in Italy. PATIENTS 538 consecutive outpatients with a first episode of acute proximal DVT at completion of an uneventful 3-month period of anticoagulation. INTERVENTION Patients were randomly assigned (stratified by center and secondary vs. unprovoked DVT by using a computer-generated list that was accessible only to a trial nurse) to fixed-duration anticoagulation (no further anticoagulation for secondary thrombosis and an extra 3 months for unprovoked thrombosis) or flexible-duration, ultrasonography-guided anticoagulation (no further anticoagulation in patients with recanalized veins and continued anticoagulation in all other patients for up to 9 months for secondary DVT and up to 21 months for unprovoked thrombosis). For the primary outcome assessment, 530 patients completed the trial. MEASUREMENTS The rate of confirmed recurrent VTE during 33 months of follow-up. RESULTS Overall, 46 (17.2%) of 268 patients allocated to fixed-duration anticoagulation and 32 (11.9%) of 270 patients allocated to flexible-duration anticoagulation developed recurrent VTE (adjusted hazard ratio [HR], 0.64 [95% CI, 0.39 to 0.99]). For patients with unprovoked DVT, the adjusted HR was 0.61 (CI, 0.36 to 1.02) and 0.81 (CI, 0.32 to 2.06) for those with secondary DVT. Major bleeding occurred in 2 (0.7%) patients in the fixed-duration group and 4 (1.5%) patients in the flexible-duration group (P = 0.67). LIMITATIONS The trial lacked a double-blind design. The sample size was not powered to detect differences in bleeding between groups and to detect effectiveness of the intervention in the subgroups of patients with unprovoked and secondary DVT. Patients with previous thromboembolism, permanent risk factors for thrombosis, and thrombophilic abnormalities other than factor V Leiden and prothrombin mutation were excluded. CONCLUSION Tailoring the duration of anticoagulation on the basis of ultrasonography findings reduces the rate of recurrent VTE in adults with proximal DVT. PRIMARY FUNDING SOURCE None.

Fibromuscular dysplasia (FMD) represents a group of non-atherosclerotic, non-inflammatory arterial diseases that most commonly involve renal and carotid arteries. Histological classification discriminates three main subtypes (intimal, medial and perimedial), which may be associated in the same patient. Although the etiology of FMD is not well understood, several mechanisms have been proposed, such as genetic predisposition, hormonal factors, paucity of vasa vasorum, repeated microtrauma, inadequate hormonal background, α-antitrypsin deficiency and arterial wall ischemia.1 The molecular biology of FMD is unclear. Pathology seems to be characterized by smooth muscle hyperplasia, elastic fiber destruction, fibrous tissue proliferation and arterial wall disorganization. Angiographic classification includes a multifocal type (with multiple stenoses) and the string-of-beads pattern (related to medial FMD), and tubular and focal types (which are not clearly related to specific histological lesions).

Fibromuscular dysplasia (FMD) reminds of a rare form of secondary arterial hypertension occurring in young people and involving the renal arteries. FMD may also involve vertebral, subclavian, mesenteric, iliac arteries and carotid arteries. FMD of internal carotid arteries is a rare finding that is frequently incidental and asymptomatic. It usually occurs in middle-aged women and is secondary to media-intima fibrodysplasia. The carotid artery may be elongated or kinked and associated cerebral aneurysms have been reported. Symptoms including transient ischaemic attack or stroke are uncommon and are related to decrease of blood flow or embolization by platelet aggregates. At the onset, differential diagnosis with vasculitis must be placed. Computed tomography or magnetic resonance imaging (MRI) angiography demonstrates bilateral high-grade stenosis with the characteristic "string of beads" pattern. Antiplatelet medication is the accepted therapy for asymptomatic lesions. Graduated endoluminal surgical dilation is an outmoded therapy, no longer used in most medical centres. Current percutaneous angioplasty is the preferred treatment for symptomatic carotid FMD, but no randomized controlled trials comparing this methodology with surgery is available. The management of a case of arterial systemic FMD in a 52-year-old women, diagnosed after a hypertensive crysis, is discussed. Imaging methods disclosed stenoses of carotid arteries, of celiac tripod and of superior mesenteric artery. Because of high risk associated to endovascular surgery, medical therapy was started. In the first year of follow-up, no events have been reported.

Background: These days no codified multidisciplinary protocol has been reported to manage all the different patent foramen ovale (PFO)-mediated syndromes. We sought to propose a multidisciplinary program of diagnosis, treatment, and follow-up of all PFO-mediated syndromes based on an in-hospital multidisciplinary task force and to review the activities during the first year. Methods: From September 2004, we organized in our hospital, a 600-bed tertiary hospital, a management program for PFO-mediated syndromes based on a task force composed of cardiologists, neurologists, and internists. Different levels of protocols were created in order to cover diagnosis, treatment, and follow-up of PFO-mediated syndromes. We reviewed the activity of our program in the first year up to September 2005. Results: Thirty-five patients (23 female, mean age 65 ± 24 years) were evaluated for suspected PFO-mediated syndromes: 20 for cryptogenic stroke, 2 for peripheral and coronary embolisms, 3 for platypnea-orthodeoxia, 9 for emicrania with aura, and 1 with hypoxiemia during neurosurgical intervention in the posterior cranial fossa. Diagnosis of PFO was confirmed in 25 patients. According to the multidisciplinary protocols, 15 patients failed to meet the requirements for transcatheter closure and were left in medical therapy whereas 11 patients (7 patients with PFO, 2 with multiperforated ASD, and 2 with a secundum ASD) underwent transcatheter closure. After a mean follow-up of 10.8 ± 4.9 months, no recurrent PFO syndromes were noted in patients treated with devices. Conclusion: The first year of our multidisciplinary program allowed a reasonable and potentially successful approach for correctly identifying patients with PFO-mediated syndromes until randomized studies are completed.