Starting dose and dose adjustment of non-vitamin K antagonist oral anticoagulation agents in a nationwide cohort of patients with atrial fibrillation.

This study aims to provide real-world data about starting-dose of NOACs and dose-adjustment in patients with atrial fibrillation (AF). In fact, even if new oral anticoagulation agents (NOACs) have a predictable effect without need for regular monitoring, dose-adjustments should be performed according to the summary of product information and international guidelines. We employed the Italian Medicines Agency monitoring registries comprising data on a nationwide cohort of patients with AF treated with NOACs from 2013 to 2018. Logistic regression analysis was used to evaluate the determinants of dosage choice. During the reference period, treatment was commenced for 866,539 patients. Forty-five percent of the first prescriptions were dispensed at a reduced dose (dabigatran 60.3%, edoxaban 45.2%, apixaban 40.9%, rivaroxaban 37.4%). The prescription of reduced dose was associated with older age, renal disease, bleeding risk and the concomitant use of drugs predisposing to bleeding, but not with CHA2DS2-VASc and HAS-BLED. A relative reduction of the proportion of patients treated with low dosages was evident overtime for dabigatran and rivaroxaban; whereas prescription of low dose apixaban and edoxaban increased progressively among elderly patients. Evidence based on real-world data shows a high frequency of low dose prescriptions of NOACs in AF patients. Except for older age, renal disease, bleeding risk and the concomitant use of drugs predisposing to bleeding, other factors that may determine the choice of reduced dose could not be ascertained. There may be potential under-treatment of AF patients, but further evaluation is warranted.

Non-vitamin K antagonist oral anticoagulation agents in patients with atrial fibrillation: Insights from Italian monitoring registries.

BACKGROUND: Atrial fibrillation (AF) is the most common cardiac arrhythmia associated with an increased risk of stroke and thromboembolism. Anticoagulation with Vitamin K antagonists (VKAs) or with novel oral anti-coagulants (NOACs) represents the cornerstone of the pharmacological treatment to reduce the risk of thromboembolism. This study aims to provide real-world data from a whole large European country about NOAC use in "non-valvular atrial fibrillation" (NVAF). METHODS: We analysed the Italian Medicines Agency (AIFA) monitoring registries collecting data of a nationwide cohort of patients with "NVAF" treated with NOACs. Using logistic regression analysis, baseline characteristics and treatment discontinuation information were compared among initiators of the 4 NOACs. RESULTS: In the reference period, the NOAC database collected data for 683,172 patients. The median age was 78 years with 19.5% aged 85 or older. Overall, the treatments were in accordance with guidelines. About 1/3 of patients switched from a prior VKA treatment; in the 72.3% of cases, these patients had a labile International Normalized Ratio (INR) at first prescription. The most prescribed NOAC was rivaroxaban, followed by apixaban, dabigatran and edoxaban. CONCLUSIONS: This study is the largest European real-world study ever published on NOACs. It includes all Italian patients treated with NOACs since 2013 accounting for about 1/3 of subjects with AF. The enrolled population consisted of very elderly patients, at high risk of ischemic adverse events. The AIFA registries are consolidated tools that guarantee the appropriateness of prescription and provide important information for the governance of National Health System by collecting real-world data.

Perioperative dental screening and treatment in patients undergoing cardiothoracic surgery and interventional cardiovascular procedures. A consensus report based on RAND/UCLA methodology.

AIM: To reach a consensus on a consistent strategy to adopt when screening patients for dental/periodontal infections and on the feasibility of providing dental treatment before cardiothoracic surgery, cardiovascular surgery or other cardiovascular invasive procedures. METHODOLOGY: A panel of experts from six Italian scientific societies was created. The deliberations of the panel were based on the RAND method. From an initial systematic literature review, it became clear that a consensually validated protocol for the reproducible dental screening of patients awaiting cardiac interventions was considered mandatory by professionals with expertise in the dental, cardiologic and cardiac surgery areas. However, a systematic review also concluded that the treatment options to be provided, their prognosis and timing in relation to the physical condition of patients, had never been defined. Following the systematic review, several fundamental questions were generated. The panel was divided into two working groups each of which produced documents that addressed the topic and which were subsequently used to generate a questionnaire. Each member of the panel completed the questionnaire independently, and then, a panel discussion was held to reach a consensus on how best to manage patients with dental/periodontal infections who were awaiting invasive cardiac procedures. RESULTS: A high level of agreement was reached regarding all the items on the questionnaire, and each of the clinical questions formulated were answered. Three tables were created which can be used to generate a useful tool to provide standardized dental/periodontal screening of patients undergoing elective cardiovascular interventions and to summarize both the possible oral and cardiovascular conditions of the patient and the timing available for the procedures considered. CONCLUSIONS: Upon publication of this consensus document, the dissemination of the information to a wide dental and cardiac audience should commence. The authors hope that this consensus will become a model for the development of a dedicated protocol, ideally usable by heart and dental teams in the pre-interventional preparation phase.

Perioperative dental screening and treatment in patients undergoing cardio-thoracic surgery and interventional cardiovascular procedures. A consensus report based on RAND/UCLA methodology.

AIM: To reach a consensus on a consistent strategy to adopt when screening patients for dental/periodontal infections, and on the feasibility of providing dental treatment before cardiothoracic surgery, cardiovascular surgery or other cardiovascular invasive procedures. METHODOLOGY: A panel of experts from six Italian scientific societies was created. The deliberations of the panel were based on the RAND method. From an initial systematic literature review, it became clear that a consensually validated protocol for the reproducible dental screening of patients awaiting cardiac interventions was considered mandatory by professionals with expertise in the dental, cardiologic and cardiac surgery areas. However, systematic review also concluded that the treatment options to be provided, their prognosis and timing in relation to the physical condition of patients had never been defined. Following the systematic review several fundamental questions were generated. The panel was divided into two working groups each of which produced documents that addressed the topic and which were subsequently used to generate a questionnaire. Each member of the panel completed the questionnaire independently and then a panel discussion was held to reach a consensus on how best to manage patients with dental/periodontal infections who were awaiting invasive cardiac procedures. RESULTS: A high level of agreement was reached regarding all the items on the questionnaire, and each of the clinical questions formulated were answered. Three tables were created which can be used to generate a useful tool to provide standardized dental/periodontal screening of patients undergoing elective cardiovascular interventions, and to summarize both the possible oral and cardiovascular conditions of the patient and the timing available for the procedures considered. CONCLUSIONS: Upon publication of this consensus document, the dissemination of the information to a wide dental and cardiac audience should commence. The authors hope that this consensus can become a model for the development of a dedicated protocol, ideally usable by heart and dental teams in the pre-interventional preparation phase.

Circulating cardiovascular biomarkers in recurrent atrial fibrillation: data from the GISSI-atrial fibrillation trial.

OBJECTIVE: we evaluated the prognostic role of circulating cardiovascular biomarkers in patients with a history of recent atrial fibrillation (AF). BACKGROUND: predicting long-term maintenance of sinus rhythm in patients with AF is difficult. METHODS: plasma concentrations of three specific cardiac markers [high-sensitivity troponin T (hsTnT), N-terminal probrain natriuretic peptide (NT-proBNP) and mid-regional proatrial natriuretic peptide (MR-proANP)] and three stable fragments of vasoactive peptides [mid-regional proadrenomedullin (MR-proADM), copeptin (CT-proAVP) and CT-proendothelin-1 (CT-proET-1)] were measured at baseline and after 6 and 12 months in 382 patients enrolled in the GISSI-AF study, a prospective randomized trial to determine the effect of valsartan to reduce the recurrence of AF. The association between these markers, clinical characteristics and recurrence of AF was tested by univariate and multivariate Cox models. RESULTS: mean patient age was 68 ± 9 years (37.2% females). A total of 84.8% of patients had a history of hypertension. In total, 59.7% qualified for history of AF because of successful cardioversion, 11.8% because of two or more episodes of AF in the 6 months preceding randomization and 28.5% because of both. Patients in AF at 6 or 12 months (203 (53.1%) with first recurrence) had significantly higher concentrations of most biomarkers. Despite low baseline levels, higher concentrations of hsTnT {adjusted hazard ratio (HR) [95% confidence intervals (CIs) for 1 SD increment] (1.15 [1.04-1.28], P = 0.007), MR-proANP (1.15 [1.01-1.30], P = 0.04), NT-proBNP (1.24 [1.11-1.39], P = 0.0001) and CT-proET-1 (1.16 [1.01-1.33], P = 0.03) independently predicted higher risk of a first recurrence of AF. Changes over time of MR-proANP tended to predict subsequent recurrence (adjusted HR [95%CI]) (1.53 [0.98-2.37], P = 0.06). CONCLUSION: circulating markers of cardiomyocyte injury/strain and endothelin are related to recurrence of AF in patients in sinus rhythm with a history of recent AF.

[Fascicular ventricular tachycardia]. / La tachicardia ventricolare fascicolare.

Fascicular tachycardia is an uncommon idiopathic ventricular tachycardia, originating from the left ventricle; it usually occurs in young male patients, with a high prevalence in south-east Asiatic people. Electrocardiographic aspects of this unique ventricular tachycardia (right bundle branch block morphology and left or right-axis deviation, with a moderate QRS widening) and verapamil sensitivity make it often difficult the differential diagnosis with other forms of supraventricular tachycardia. Reentry is believed to be the operative mechanism of fascicular tachycardia, with the reentrant circuit located in the Purkinje network, in the region of the left posterior or anterior fascicle. The slow conduction zone participating in the reentry circuit, made up of partially depolarized Purkinje fibers, seems to be located in a relatively wide area, from the basal to the apical left interventricular septum. Intravenous verapamil is elective in acute treatment; however oral verapamil shows poor efficacy in preventing tachycardia relapses. Ablative approach is very effective; success is achieved in approximately 90% of patients, with rare complications. Recently diastolic potentials during fascicular tachycardia have been reported and these findings have given rise to new electrophysiological hypotheses and new indications about the successful ablation site.

Hypertension and ischemic heart disease. Role of dipyridamole echocardiography test.

The aim of this study is to try to evaluate the relationship between arterial hypertension and ischemic heart disease (IHD) in the light of the physiopathologic response pattern to the dipyridamole echocardiography test (DET) in hypertensive patients, in pharmacologic washout, without any electrocardiographic ST segment depression during exercise tests or at rest. Sixty patients affected by mild to moderate asymptomatic essential arterial hypertension were studied: the subjects had a sitting diastolic blood pressure > or = 95 < or = 114 mmHg; there were 38 men and 22 women with a mean age of 49.8 +/- 7.6 years (range twenty-nine to sixty-eight). All patients had undergone high-dose DET (0.84 mg/kg in ten minutes). No patients developed side effects or asynergy in cardiac contractility during the test. In the absence of any significant coronary artery obstruction assessed angiographically, 18 patients (30%) showed ST segment depression > 1.0 mV during DET, sometimes with the presence of ventricular and/or supraventricular extrasystoles. In this group of patients the left ventricular mass index (LVMI) and duration of hypertension (in months) were higher as compared with those of the other 42 patients (respectively: 160.2 +/- 5.1 vs 129.2 +/- 9.2 g/m2, P < 0.02; and 30 +/- 4.8 vs 9 +/- 5.4 months, P < 0.007). In conclusion it is reasonable to speculate from these data that the ischemic-like" dipyridamole-induced ST segment depression, like that shown by patients affected by Syndrome X, might involve a worse prognosis in hypertensive patients. This may be because of increased coronary resistance due to structural modification or anatomic background.

Calcium antagonist antihypertensive treatment of non-insulin-dependent diabetics: efficacy and safety of lacidipine versus nifedipine SR.

Arterial hypertension is a chronic condition regarded as one of the main risk factors for development of coronary atherosclerosis. As dyslipidemia and reduced glucose tolerance are also risk factors for coronary disease, it is considered important to use antihypertensive drugs having no negative effects on lipid and glucose metabolism when diabetic patients are treated for hypertension. Lacidipine, a new dihydropyridine-like calcium antagonist, has been shown in in vivo and in vitro preclinical studies to possess potent, long-lasting antihypertensive activity. The present study compared the efficacy and safety of once-daily treatment with lacidipine versus nifedipine SR given twice-daily in non-insulin-dependent diabetic patients. Results have shown a similar efficacy of the two treatments: 6 months later, both drugs had reduced blood pressure values [lacidipine from 184.8/105.2 mm Hg to 144.4/87.1 mm Hg; nifedipine slow-release (SR) from 182.3/106.8 mm Hg to 143.6/89.4 mmHg]. However, lacidipine exhibited a lower incidence of adverse events (particularly ankle edema and tachycardia) than nifedipine SR. Finally, both treatments showed no negative effect on metabolic parameters (total cholesterol, high-density lipoprotein cholesterol, triglycerides, and blood glucose).

[The role of Doppler echocardiography in assessing left ventricular diastolic function. Case histories]. / Ruolo dell'ecocardiografia Doppler nella valutazione della funzione diastolica ventricolare sinistra. Contributo casistico.

The aim of this study was to provide a further contribution to evaluate the alterations induced by age on a number of simple Doppler indexes of left ventricular diastolic function. A population of 48 healthy subjects aged between 15 and 78 years old was examined using pulsed Doppler analysis of the left ventricular refilling flow. Linear regression analysis revealed a significant inverse correlation between age and peak speed during rapid refilling (r = -0.80); between age and the ratio between peak speed during rapid refilling and peak during atrial systole (r = -0.92); between age and deceleration time of peak E wave speed, although on the contrary the peak speed of diastolic refilling flow during the atrial systole (r = 0.81) increased significantly with age. Variance analysis showed that indexes of left ventricular diastolic function and age continued on the contrary to be significant n the population as a whole and in both sexes. From these findings it is clear that in the different age groups (15-29, 30-49, 50-65, and over 65) the peak speed of rapid refilling flow was significantly lower in over-65-year-olds than in elderly, middle-aged and young subjects (55 +/- 0.8, 60 +/- 0.5, 65 +/- 0.7 and 75 +/- 0.6 respectively; p < 0.001). The ratio between the peak speed of rapid refilling and that during the atrial systole was lower in over-65-year-olds compared to elderly subjects, middle-aged subjects or the youngest age group (0.94 +/- 0.09, 1.05 +/- 0.13, 1.96 +/- 0.21 and 2.68 +/- 0.50 respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

[3 cases of gingival hyperplasia during nifedipine therapy]. / Su tre casi di iperplasia gengivale in corso di terapia con Nifedipina.

The authors report the cases of three male patients, aged 36, 54 and 52 years, who developed gingival hypertrophy during treatment with nifedipine at a dose of 40 mg/daily. Hypertrophy was the same as that observed in patients treated with anti-convulsive or cytostatic drugs, and may probably be due to interference with calcium ions and local factors. Full recovery was achieved by suspending nifedipine treatment in all patients.

[The diagnostic value of delta-R and delta-Q as positive criteria of the ergometry test in a group of patients with angina pectoris of effort]. / Valore diagnostico del delta-R e del delta-Q come criteri di positività del test ergometrico in un gruppo di pazienti con angina da sforzo.

ECG-exercise tests were performed in 29 patients affected by effort chest pain. All patients underwent coronary angiography and/or revealed positive results in the cycloergometer effort test. The aim of the study was to evaluate ultrasonic variations in the R and Q waves due to maximal effort, so as to increase the information provided by the effort ECG. In the coronary angiographic test, 21 out of 29 patients revealed significant hemodynamic coronary stenosis; 10 patients were affected by previous myocardial necrosis; 8 patients showed no hemodynamic coronary lesions (OV). In the OV patients a statistically significant increase was observed in the Q wave at maximal effort in comparison with average basal values; on the other hand, there was a decrease, although not significant, in voltage at peak effort in patients with coronary stenosis. R wave amplitude was smaller in comparison to basal values in OV patients, while a significant increase was observed in the 21 patients with coronary lesions.

Captopril at 50 mg as well as at 100 mg once a day reduces blood pressure for up to 24 h: a double-blind randomized crossover study in mild to moderate hypertensives.

The extent and the duration of the antihypertensive effect of captopril, given once a day at a dose of 50 mg, compared with placebo and with the 100 mg once daily dose was studied in 30 mild or moderate uncomplicated essential hypertensives (mean +/- s.e.m. age 52.0 +/- 1.5 years), who responded (mean blood pressure decrease greater than 10%) to a single oral dose (12.5 mg) of captopril. According to a randomized, double-blind, crossover design, they were given 50 mg captopril four times a day, 100 mg captopril four times a day or matched placebo for 1 month. At the end of each treatment period blood pressure and heart rate were measured every 30 min from 3 h before to 2 h after the last dose. Although the heart rate did not change, mean blood pressure after the 50- and 100-mg doses of captopril was consistently significantly (P less than or equal to 0.05) lower than after placebo. The hypotensive effect peaked at the second hour and was still significant 24 h after dosing without any significant differences between the 50- and the 100-mg doses. These findings indicate that captopril, given chronically once a day at a dose of 50 mg to mild to moderate hypertensive responders, exerts its hypotensive effect up to 24 h and that doubling the dose does not increase either the extent or the duration of its action.