A Structured Literature Review and International Consensus Validation of FORTA Labels of Oral Anticoagulants for Long-Term Treatment of Atrial Fibrillation in Older Patients (OAC-FORTA 2019).

INTRODUCTION: Evidence regarding safety and efficacy of oral anticoagulants for the treatment of atrial fibrillation (AFib) in older adults has been assessed regarding the age appropriateness of oral anticoagulants (OAC) according to the FORTA (Fit fOR The Aged) classification (OAC-FORTA). Three years after its first version (OAC-FORTA 2016), an update was initiated to create OAC-FORTA 2019. METHODS: A structured review of randomized controlled clinical trials and summaries of individual product characteristics was performed to detect newly emerged evidence on oral anticoagulants in older patients with AFib. This review was used by an interdisciplinary panel of European experts (N = 10) in a Delphi process to label OACs according to FORTA. RESULTS: A total of 202 records were identified and 11 studies finally included. We found four new trials providing relevant data on efficacy and safety of warfarin, apixaban, dabigatran or rivaroxaban in older patients with AFib. In the majority of studies comparing the non-vitamin-K oral anticoagulants (NOACs) with warfarin, NOACs were superior to warfarin regarding at least one relevant clinical endpoint. The mean consensus coefficient significantly increased from 0.867 (OAC-FORTA 2016) to 0.931 (p < 0.05) and the proposed FORTA classes were confirmed in all cases during the first round (consensus coefficient > 0.8). Warfarin, dabigatran, edoxaban and rivaroxaban were assigned to the FORTA B label, acenocoumarol, fluindione and phenprocoumon were labeled FORTA C and only apixaban was rated as FORTA A. CONCLUSION: OAC-FORTA 2019 confirms that AFib can be successfully treated with positively labeled antithrombotics at advanced age.

Appropriateness of Oral Anticoagulants for the Long-Term Treatment of Atrial Fibrillation in Older People: Results of an Evidence-Based Review and International Consensus Validation Process (OAC-FORTA 2016).

BACKGROUND: Age appropriateness of anticoagulants for stroke prevention in atrial fibrillation is uncertain. OBJECTIVE: To review oral anticoagulants for the treatment of atrial fibrillation in older (age >65 years) people and to classify appropriate and inappropriate drugs based on efficacy, safety and tolerability using the Fit-fOR-The-Aged (FORTA) classification. METHODS: We performed a structured comprehensive review of controlled clinical trials and summaries of individual product characteristics to assess study and total patient numbers, quality of major outcome data and data of geriatric relevance. The resulting evidence was discussed in a round table with an interdisciplinary panel of ten European experts. Decisions on age appropriateness were made using a Delphi process. RESULTS: For the eight drugs included, 380 citations were identified. The primary outcome results were reported in 32 clinical trials with explicit and relevant data on older people. Though over 24,000 patients aged >75/80 years were studied for warfarin, data on geriatric syndromes were rare (two studies reporting on frailty/falls/mental status) and missing for all other compounds. Apixaban was rated FORTA-A (highly beneficial). Other non-vitamin K antagonist oral anticoagulants (including low/high-intensity dabigatran and high-intensity edoxaban) and warfarin were assigned to FORTA-B (beneficial). Phenprocoumon, acenocoumarol and fluindione were rated FORTA-C (questionable), mainly reflecting the absence of data. CONCLUSIONS: All non-vitamin K antagonist oral anticoagulants and warfarin were classified as beneficial or very beneficial in older persons (FORTA-A or -B), underlining the overall positive assessment of the risk/benefit ratio for these drugs. For other vitamin-K antagonists regionally used in Europe, the lack of evidence should challenge current practice.

Anemia and iron deficiency in heart failure.

Heart failure is a common problem and a major cause of mortality, morbidity and impaired quality of life. Anemia is a frequent comorbidity in heart failure and further worsens prognosis and disability. Regardless of anemia status, iron deficiency is a common and usually unidentified problem in patients with heart failure. This article reviews the mechanisms, impact on outcomes and treatment of anemia and iron deficiency in patients with heart failure.

Acute coronary syndrome of paradoxical origin.

We describe a rare case of acute myocardial infarction secondary to paradoxical embolism complicating acute pulmonary embolism. A 44-year-old woman presented to the emergency department with chest pain. The physical examination was unremarkable except for oxygen saturation of 75%, and the electrocardiogram showed ST-segment elevation in the inferior leads. Urgent coronary angiography showed a distal occlusion of the right coronary artery and multiple thrombi were aspirated. Despite relief of chest pain and electrocardiogram normalization, her oxygen saturation remained low (90%) with high-flow oxygen by mask. The transthoracic echocardiogram showed a mass in the left atrium and dilatation of the right chambers, while the transesophageal echocardiogram showed a thrombus attached to the interatrial septum in the region of the foramen ovale. Color flow imaging was consistent with a patent foramen ovale. Thoracic computed tomography angiography documented thrombi in both branches of the pulmonary trunk. After five days on anticoagulation, the patient underwent surgical foramen ovale closure.

Density functional theory study of the oxoperoxo vanadium(V) complexes of glycolic acid. Structural correlations with NMR chemical shifts.

The DFT B3LYP/SBKJC method has been used to calculate the gas-phase optimized geometries of the glycolate oxoperoxo vanadium(V) complexes [V(2)O(2)(OO)(2)(gly)(2)](2-), [V(2)O(3)(OO)(gly)(2)](2-) and [VO(OO)(gly)(H(2)O)](-). The (51)V, (17)O, (13)C and (1)H chemical shifts have been calculated for the theoretical geometries in all-electron DFT calculations at the UDFT-IGLO-PW91 level and have been subsequently compared with the experimental chemical shifts in solution. In spite of being applied to the isolated molecules, the calculations allowed satisfactory reproduction of the multinuclear NMR solution chemical shifts of the complexes, suggesting that the theoretical structures are probably close to those in solution. The effects of structural changes on the (51)V and (17)O NMR chemical shifts have been analysed using the referred computational methodologies for one of the glycolate complexes and for several small molecules taken as models. These calculations showed that structural modifications far from the metal nucleus do not significantly affect the metal chemical shift. This finding explains why it is possible to establish reference scales that correlate the type of complex (type of metal centre associated with a certain type of ligand) with its typical region of metal chemical shifts. It has also been found that the V[double bond, length as m-dash]O bond length is the dominant geometrical parameter determining both delta(51)V and the oxo delta(17)O in this kind of complex.

Cardiovascular risk associated with interruption of antiplatelet and oral anticoagulation therapy.

A number of clinical situations are associated with increased risk for atherothrombosis (for example coronary stents) or thromboembolism (such as mechanical heart valves). Large numbers of patients are under regular medication with antiplatelet agents or anticoagulants, which carries an increased hemorrhagic risk in the setting of a surgical procedure. On the other hand, the interruption of antithrombotic drugs restores the risk of the baseline condition and puts the patient in a vulnerable situation. The authors review the recent literature on this topic and propose practical algorithms to help clinical decisions.

NMR and DFT studies of the complexation of W(VI) and Mo(VI) with 3-phospho-D-glyceric and 2-phospho-D-glyceric acids.

Multinuclear ((1)H, (13)C, (17)O, (31)P, (95)Mo, (183)W) magnetic resonance spectroscopy (1D and 2D) has been used to study the complexation of molybdate(VI) and tungstate(VI) with 3-phospho-D-glyceric and 2-phospho-D-glyceric acids. 3-Phospho-D-glyceric acid forms four and five complexes, respectively, with molybdate and tungstate. These have MO(2)(2+) centres, and involve the carboxylate and the adjacent OH groups. Two isomeric 1:2 (metal-ligand) complexes are detected, in addition to one mononuclear species having MO(3) centres and involving the ligand in a tridentate chelation and a dominant 12:4 species with both tungstate(VI) and molybdate(VI). The dominant 12:4 species can be seen as two 1:2 complexes bound together in a ring through two diphosphometalate moieties, derived from heptamolybdate or heptatungstate, respectively, by inclusion of two phosphate groups from the ligands. Tungstate is also able to form an additional 2:1 tridentate species. 2-Phospho-D-glyceric acid does not interact with tungstate but is able to form one phosphomolybdate species with molybdate, which can be regarded as a heptamolybdate derivative. Density functional theory (DFT) calculations were performed for 1:2 complexes, including calculations on the relative energies of the 1:2 complexes detected in related systems, to validate previously proposed structures. The results are compared with those obtained from multinuclear NMR spectroscopy.

Combined myocardial infarction: two case reports.

Combined myocardial infarction is defined as a current of injury on the electrocardiogram in both inferior and anterior leads. From a pathophysiological standpoint, this indicates simultaneous acute transmural ischemia of contralateral vascular territories. The authors present the cases of two patients admitted with this rare type of infarction, followed by a discussion of the relationship between electrocardiographic and angiographic findings and their value for assessing prognosis in this clinical entity.

Oxoperoxo vanadium(V) complexes of L-lactic acid: density functional theory study of structure and NMR chemical shifts.

Various combinations of density functionals and pseudopotentials with associated valence basis-sets are compared for reproducing the known solid-state structure of [V 2O 2(OO) 2 l-lact 2] (2-) cis . Gas-phase optimizations at the B3LYP/SBKJC level have been found to provide a structure that is close to that seen in the solid state by X-ray diffraction. Although this may result in part from error compensation, this optimized structure allowed satisfactory reproduction of solution multinuclear NMR chemical shifts of the complex in all-electron DFT-IGLO calculations (UDFT-IGLO-PW91 level), suggesting that it is probably close to that found in solution. This combination of approaches has subsequently been used to optimize the structures of the vanadium oxoperoxo complexes [V 2O 3(OO) l-lact 2] (2-) cis , [V 2O 3(OO) l-lact 2] (2-) trans , and [VO(OO)( l-lact)(H 2O)] (-) cis . The (1)H, (13)C, (51)V, and (17)O NMR chemical shifts for these complexes have been calculated and compared with the experimental solution chemical shifts. Excellent agreement is seen with the (13)C chemical shifts, while somewhat inferior agreement is found for (1)H shifts. The (51)V and (17)O chemical shifts of the dioxo vanadium centers are well reproduced, with differences between theoretical and experimental shifts ranging from 22.9 to 35.6 ppm and from 25.1 to 43.7 ppm, respectively. Inferior agreement is found for oxoperoxo vanadium centers, with differences varying from 137.3 to 175.0 ppm for (51)V shifts and from 148.7 to 167.0 ppm for (17)O(oxo) shifts. The larger errors are likely to be due to overestimated peroxo O-O distances. The chosen methodology is able to predict and analyze a number of interesting structural features for vanadium(V) oxoperoxocomplexes of alpha-hydroxycarboxylic acids.

Left ventricular noncompaction: case report and literature review.

Isolated left ventricular noncompaction (ILVNC) is a rare cause of dilated cardiomyopathy. It is morphologically characterized by a spongy left ventricle with prominent myocardial trabeculations. Although not proven, it is nowadays widely accepted that ILVNC results from arrest of the normal myocardial compaction process during early embryonic life. ILVNC can occur in a familial form and certain genes coding proteins linking the extracellular matrix and the cytoskeleton have been related to this disorder. Clinically, the disease courses with heart failure, embolic and arrhythmic events being a common cause of morbidity and mortality. Current diagnostic criteria for ILVNC are based on clinical and echocardiographic data. Therapy is based on current heart failure guidelines, with particular emphasis on anticoagulation and prevention of fatal arrhythmias. The authors describe the case of a 29-year-old man admitted to the Cardiology Department with decompensated heart failure (NYHA IV), a dilated left ventricle with severe systolic dysfunction, an apical thrombus and highly trabeculated walls. Clinical evolution was favorable after standard pharmacologic therapy for heart failure and levosimendan, the patient being discharged in NYHA class I-II. Eighteen months later, despite partial recovery of left ventricular systolic function, the patient suffered sudden death. A review and discussion of the literature presented regarding etiopathogenesis, diagnostic criteria and therapeutic options.

Specialized acute care and heart failure management programs.

When patients with acute heart failure are treated by specialist teams in dedicated units, there are gains in terms of adherence to guidelines, with corresponding clinical and prognostic benefits. Extending this specialized care to heart failure management programs, with multidisciplinary teams headed by doctors but with a strong nursing component and in conjunction with other levels of care, leads to further gains for patients and for the efficiency of the health system as a whole.

Ischemic stroke complicating cardiac catherization: case report.

Ischemic stroke occurs in 0.2-0.4% of patients undergoing left heart catheterization, and is responsible for 5-10% of the mortality associated with the procedure. The main predisposing factors for this complication are female gender, complex atherosclerotic plaques in the ascending aorta, and peripheral arterial disease. The possibility of timely intervention with reperfusion therapy supports close clinical monitoring during the immediate post-catheterization period. The cardiologist should be familiar with the various types of stroke reperfusion therapy and its indications according to the time interval between catheterization and the stroke. The decision should be discussed with neurology and neuroradiology.

How to design a clinical in cardiology. The main issues.

Accumulated clinical experience, arising from consecutive observation of patients, produces biased evaluations of drug efficacy. Only properly designed clinical trials can minimize bias and evaluate drug efficacy. However, clinical experience can be useful in clinical trial planning. The authors review the main aspects of the methodology of clinical trials in cardiology, namely the different phases of clinical research in humans, definition of the population, how to avoid bias, design and randomization options, determination of sample size, outcome types, and precautions to be taken during follow-up.

Multinuclear NMR study of the complexes of 6-phospho-D-gluconic acid with W(VI) and Mo(VI).

Multinuclear ((1)H, (13)C, (17)O, (31)P, (95)Mo, (183)W) magnetic resonance spectroscopy (1D and 2D) has been used to show that 6-phospho-d-gluconic acid forms three complexes with tungsten(VI) and six complexes with molybdenum(VI) in aqueous solution, depending on pH and concentration. Two isomeric 1:2 (metal-ligand) complexes are detected both with tungstate(VI) and molybdate(VI), having MO(2)(2+) centres and involving the carboxylate and the adjacent OH groups in addition to one 2:1 (metal-ligand) complex possessing a M(2)O(5)(2+) centre, with the ligand being coordinated by the carboxylate group and the three consecutive OH groups in positions 2, 3 and 4. Molybdate(VI) forms three additional species, which are not detected with tungstate. One of them is a 2:1 complex with a Mo(2)O(5)(2+) centre, with the ligand being tetradentate via O-3, O-4, O-5 and the phosphate group. The other two are 12:4 species, which can be seen as two 1:2 complexes bound together in a ring through two diphosphomolybdate moieties each derived from heptamolybdate by inclusion of two phosphate groups from the ligands.