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Aims: Since the introduction of direct oral anticoagulant (DOAC) for atrial fibrillation (AF) therapy, inappropriate and/or underdosing of these drugs has been a major clinical challenge. We evaluated the characteristics of patients with AF treated with inappropriate and low-dose DOACs., Methods and Results: Patients with AF treated with inappropriate and low-dose DOACs from October 2021 to December 2021 were evaluated from the French National Prospective Registry (PAFF). We evaluated 1890 patients with AF receiving DOACs (apixaban 55%, dabigatran 7%, and rivaroxaban 38%). Inappropriate dosing was noted in 18% of the population. Patients with appropriate dosing had less comorbidities: younger age (75 ± 10 vs. 82 ± 8 years old, P < 0.0001), reduced chronic renal failure (26 vs. 61%, P < 0.0001), and lower CHA2DS2VASc and HASBLED scores (3 ± 2 vs. 4 ± 3, P < 0.0001; 2 ±1 vs. 2 ± 2, P < 0.0001), respectively. In multivariate analysis, older age (P < 0.0001) and a higher CHA2DS2VASc score (P = 0.0056) were independently associated with inappropriate DOAC dosing. Among 472 patients (27%) treated with low-dose rivaroxaban or apixaban, 46% were inappropriately underdosed. Patients inappropriately underdosed were younger (82.3 ± 8.4 vs. 85.9 ± 5.9 years, P < 0.0001) with less chronic renal disease (47 vs. 98%, P < 0.0001). However, these patients had higher rates of prior haemorrhagic events (18 vs. 10%, P = 0.01), clopidogrel use (11 vs. 3%, P = 0.0002), and apixaban prescription (74 vs. 50%, P < 0.0001)., Conclusion: Within this large registry, DOACs were associated with inappropriate dosing in 18% of cases. Independent predictors of inappropriate dosing were high CHA2DS2VASc scores and older age. Moreover, 46% of patients treated with low-dose DOACs were inappropriately underdosed and more frequently in patients treated with apixaban., Competing Interests: Conflict of interest: N.L. received consulting fees from Bayer and BMS-Pfizer., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Unlabelled: Between 1980 and 1995, we observed twenty-five patients (22 males, 3 females) at the mean age of 50.6 +/- 13 years, without previous myocardial infarction who presented exercise induced ST elevation on a bicycle stress test., Methods: Significant ST elevation was defined as a > or = 1 mm change present in > or = 1 lead measured 0.08 sec after the J point and in 3 consecutive beats. All patients have undergone coronary angiography in the days following the exercise test., Results: Most of patients (56%) presented a history of typical angina that was either purely exertional (8 pts) or also occurred at rest (6 pts). Others (36%) had non typical angina or no angina (8%); 78% of pts were smokers. Sixteen patients (group I) had ST elevation during exercise (exercise duration: 7.6 +/- 4 min; peak heart rate: 135.5 +/- 29 batt/min; ST = 3.5 +/- 1.5 mm) and nine (group II) during the recovery phase (exercise duration 16.3 +/- 1.6 min; p < 0.05; peak heart rate 168 +/- 22 batt/min; p < 0.05; ST: 5.8 +/- 3 mm; p < 0.05). In group I, 1 patient had no vessel disease, 12 had one vessel disease, 3 had multivessel disease with 6 cases of hypersevere coronary stenose (> 90%). In group II, 4 patients had normal coronary arteries, there was one vessel coronary artery disease in 4 patients and multivessel in one subject, without hypersevere coronary stenosis. Correlation between anatomic location of stenosis and electrocardiographic ST elevation was excellent, particularly in case of single vessel disease (100%). All patients underwent one or more new exercise tests after therapeutic intervention (surgery n = 3; angioplasty n = 7; medical treatment n = 15), only 2 patients had persistent exercise induced ST elevation. During follow-up (5 +/- 3 years), 3 patients died (2 cardiac deaths) and 3 had recurrent angina controlled by new treatment., Conclusion: Exercise-induced ST elevation is a rare phenomenon in patients without prior myocardial infarction. When occurring purely during exercise, coronary lesions are frequent and often servere, in the other hand ST elevation of the recovery phase is frequently associate with normal arteries or less severe lesions. In most cases, revascularisation or medical therapy can abolish clinical and electrocardiographic abnormalities.

Iatrogenic third degree atrioventricular block due to alpha interferon is rare. The authors present a case which occurred with low dosage, regressed when treatment was withdrawn and reappeared when treatment was reintroduced. The physiopathological mechanism of disease of the conduction pathways and its general cardiotoxicity is not yet understood. The secondary effects of this increasingly widely used anti-tumoral and anti-infectious drug should be recognised in order to prevent them. Initial cardiological investigation and follow-up are indicated to ensure this prevention.

The aim of rehabilitation is to improve exercise capacity and, thereby, the autonomy of patients with cardiac failure. For many years, these patients were considered inapt to perform physical exercise and they are in the same situation at the dawn of the year 2000 as patients with myocardial infarction forty years ago. The symptoms of cardiac failure (dyspnoea of effort and muscular fatigue) are not only the consequence of pulmonary hypertension and decreased muscular perfusion. Prolonged interruption of exercise and long stays in bed or in a chair lead to anatomical and functional amyotrophy, which, in turns, incites to further inactivity. Deconditioned respiratory muscles cannot tolerate the increased load of hyperventilation. Neurohormonal changes cause vasoconstriction which reduces muscular perfusion. Physical training can significantly improve these abnormalities, though it does not seem to have a measurable effect on cardiac function; based on segmental work which enables performance of substantial efforts with a minimum of haemodynamic changes, it provides a 20 to 30% gain in capacity, mainly increasing the duration of submaximal exercise rather than maximum performance. Muscular fatigue is the symptom which is the most improved. Unfortunately the organisation, which is more difficult than in the post-infarction period, and the generalisation of the practice of long-term, well adapted physical training remains marginal although hundreds of thousands of patients could benefit; more than the inertia of the official instances concerning anything related to cardiac rehabilitation, it is the lack of interest shown by cardiologists and the absence of flexible structures within the health care organisation for elderly people which are responsible.

The growing numbers of elderly and cardiac patients are the consequence of progress in the prevention of the complications of coronary artery and valvular heart disease by surgery and revascularisation and improved treatment of hypertension which delays target organ complications by at least fifteen years. The elderly are particularly exposed to surgical risk: nearly half the patients with ischaemic heart disease die of cancer; a high proportion of elderly people require orthopaedic surgery either as an emergency (fractured femur) or as a standard procedure (knee surgery); nearly a quarter of patients requiring peripheral vascular surgery have coronary artery disease which may be silent. A preoperative consultation with the anaesthetist has been made compulsory, except in emergencies, giving time for preoperative investigations. The decrees of the Court of Cassation have also affected the traditional relationship of trust between patients and their doctors, leading to an increase in the cost of preoperative investigations without an accurate assessment of their benefits with regards to postoperative complications and the cost that they entail. Contrary to present tendencies reflected in the literature, the screening of risks should be simplified: clinical history and examination and resting ECG, often completed by stress testing, are sufficient in the large majority of cases. More importance should be attributed to the functional status than to the lesions. When the cardiac disease is asymptomatic, the chances are that it will remain so during and after surgery.... The main difficulty is not in identifying high risk patients: it is preventing cardiovascular events when surgery is unavoidable. The experience and collaboration between the quartet of anaesthetist, surgeon, cardiologist and general practitioner, are much more useful than the very incomplete bibliographical data concerning this side of the problem.

Effort tolerance is reduced after correction of Tetralogy of Fallot. This prospective study investigated the cardiorespiratory response and the chronotropic function (mean follow-up 11.1 years) of 70 patients (43 boys and 27 girls) with an average age of 14.9 +/- 7.2 years (group 1) compared with 65 normal, sedentary subjects paired red for age and gender (group 2). All underwent exercise testing (Bruce protocol) with measurement of respiratory gases. Quantification of pulmonary regurgitation was performed by Doppler echocardiography. The chronotropic response to exercise was assessed by calculating the mean of slopes established by chronotropic metabolic relationship of Wilkoff. The cardiorespiratory response to exercise was abnormal in group 1: the duration of exercise (11.3 vs 13.6 min; p = 0.005), peak VO2 (35.5 vs 46 ml/min/kg; p < 0.001) and anareobic threshold (8.3 vs 9.2 min; p = 0.001) were decreased. Maximal heart rate (172 vs 190bpm; p < 0.001) and the mean of the metabolic-chronotropic slopes (0.68 vs 0.83; p < 0.001) were decreased in the patient group, showing abnormal chronotropic response to exercise. The latter seemed to be related to the severity of pulmonary regurgitation. The duration of exercise (10.6 vs 11.5 min; p = 0.001), peak VO2 (33 vs 37 ml/min/kg; p < 0.001), maximal heart rate (161 vs 177 bpm; p = 0.002) and the mean of the slopes of the metabolic-chronotropic relationship (0.59 vs 0.72; p < 0.001) were decreased in patients with moderate to severe pulmonary regurgitation. This study shows that significant pulmonary regurgitation is responsible for a poor cardiorespiratory response to exercise and for an abnormal chronotropic response which seems to be multifactorial but probably related to an adaptation favouring left ventricular filling during exercise.

Exercise capacity in cardiac transplanted patients has been reported to remain decreased in some studies; however, functional results after transplantation may vary, ranging from modest to spectacular improvement. The aim of the study was to quantify exercise capacity in a large series of transplanted patients and to search for factor predictive of a good functional result. Eighty-five patients (mean 52.1 +/- 11.8 years) underwent exercise testing with respiratory gas exchange measurements 1 to 100 months after transplantation. Mean performance was 112.4 +/- 33 W with a peak VO2 of 21.1 +/- 6 ml.min-1.kg-1. Heart rate was 103 +/- 14 at rest, reaching 142 +/- 22 beats.min-1 at the end of exercising. In univariate analysis, maximal or submaximal aerobic capacity parameters were strongly correlated with chronotropic reserve (r = 0.63; P < 0.001) without correlation with cold ischaemic time, number of rejection episodes or right bundle branch block. In multiple regression analysis, chronotropic reserve, time from transplantation, age of donor and age of patient were proved to be the variables best correlated with peak VO2. Our study confirms the persistence of a large decrease in aerobic functional capacity despite cardiac transplantation; limited exercise capacity does not improve over time, and is limited not only by the patient's age but by that of the donor, and especially by chronotropic reserve.

The use of sublingual nitroglycerin in the stress test is a precious tool in everyday clinical cardiology. It has several indications in this context: 1) Confirmation of the diagnosis of myocardial ischaemia by eliminating a large number of false-positives with no marked variation of ST depression and performance after sublingual nitroglycerin in contrast with patients presenting authentic myocardial ischaemia on effort. 2) Teaching of the preventive and opportunistic use of nitroglycerin before intense effort and before physical training which, in the long-term, is one of the most effective treatments of exertional angina pectoris. 3) Demonstration of potentiation of the effect of certain antianginal drugs such as beta-blockers. 4) In therapeutic trials, the stress test performed with sublingual nitroglycerin is used as a reference and to select patients capable of a fairly marked progression, so that they can be included in a protocol. It has the advantage of demonstrating a functionally measurable improvement of the stress test with an appropriate drug. 5) Progression with sublingual nitroglycerin during the stress test is related to regression of ischaemia i.e. restoration of functional viability of hibernating or shocked ischaemic segments of myocardium. It is probably the only realistic way to predict possible improvement after revascularization compared to other tests, which may be over-sensitive, as they detect zones with little capacity of regaining a viability which really contributes to cardiac output on exertion.

We report the case of a woman who, at the age of 27, developed a cerebral arterial occlusion. The laboratory investigations showed an anti-human beta2-glycoprotein I antibody, but no other biological sign of antiphospholipid antibody syndrome or autoimmune disorders. The patient otherwise presented with diabetes and moderate obesity. The species specificity of anti-beta2-glycoprotein I antibodies probably explains the discrepancy between false negative results for antiphospholipid antibodies assayed by clotting and ELISA studies and positivity for anti-human beta2-glycoprotein I. Further studies will be important to evaluate the frequency of such antibodies, as well as their value as a risk factor for venous and arterial thrombosis, and their signification within the antiphospholipid antibody syndrome.

The authors report the case of a 10 year old child who presented with an uncomplicated deep venous thrombosis associated with an antiphospholipid syndrome. The diagnosis was established by the finding of spontaneous prolongation of the activated cephalin time, the finding of a lupus-like antibody and an anti-cardiolipin antibody. The clinical outcome was good with oral anticoagulants but a recurrence was observed when they were stopped. The authors discuss the question of the duration of preventive therapy.

This study addresses the diagnostic value of two new criteria of exercise stress testing for primary coronary artery disease and restenosis after angioplasty: the slope of the linear relation between ST segment changes and heart rate during exercise; the exercise-recovery loop (clockwise direction in normal subjects and anticlockwise direction in coronary patients). These two criteria were compared with the standard diagnostic criteria (horizontal or descending ST segment depression greater than 1 mm or ascending ST segment depression greater than 2 mm) in 125 patients with suspected coronary artery disease who underwent computerised exercise stress testing and coronary angiography (30 single, 31 double and 30 triple vessel disease; 34 without significant stenosis) and in 24 patients with single vessel disease who underwent successful angioplasty and who performed exercise stress testing before, immediately after and 6 months after angioplasty before routine control coronary angiography. The sensitivity (Se), specificity (Sp), positive predictive value (PPV) of the exercise-recovery loop for the diagnosis of coronary disease were 81 %, 82 %, 89 %, respectively, versus 69 %, 71 % and 88 % for the standard criteria. The detection of restenosis by these criteria also appeared to be better (71 %, 91% and 91 % versus 46 %, 63 % and 60 %, respectively). However, for the classical threshold value of 2.4 mv/beat/min, the ST/HR criteria seemed to be less useful (Se : 80 %, Sp : 26 %).