BackgroundAtrial fibrillation is associated with higher mortality. Identification of causes of death and contemporary risk factors for all‐cause mortality may guide interventions.Methods and ResultsIn the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) study, patients with nonvalvular atrial fibrillation were randomized to rivaroxaban or dose‐adjusted warfarin. Cox proportional hazards regression with backward elimination identified factors at randomization that were independently associated with all‐cause mortality in the 14 171 participants in the intention‐to‐treat population. The median age was 73 years, and the mean CHADS 2 score was 3.5. Over 1.9 years of median follow‐up, 1214 (8.6%) patients died. Kaplan–Meier mortality rates were 4.2% at 1 year and 8.9% at 2 years. The majority of classified deaths (1081) were cardiovascular (72%), whereas only 6% were nonhemorrhagic stroke or systemic embolism. No significant difference in all‐cause mortality was observed between the rivaroxaban and warfarin arms (P=0.15). Heart failure (hazard ratio 1.51, 95% CI 1.33–1.70, P<0.0001) and age ≥75 years (hazard ratio 1.69, 95% CI 1.51–1.90, P<0.0001) were associated with higher all‐cause mortality. Multiple additional characteristics were independently associated with higher mortality, with decreasing creatinine clearance, chronic obstructive pulmonary disease, male sex, peripheral vascular disease, and diabetes being among the most strongly associated (model C‐index 0.677).ConclusionsIn a large population of patients anticoagulated for nonvalvular atrial fibrillation, ≈7 in 10 deaths were cardiovascular, whereas <1 in 10 deaths were caused by nonhemorrhagic stroke or systemic embolism. Optimal prevention and treatment of heart failure, renal impairment, chronic obstructive pulmonary disease, and diabetes may improve survival.Clinical Trial Registration URL: https://www.clinicaltrials.gov/. Unique identifier: NCT00403767.

Marabotti C, Scalzini A, Cialoni D, Passera M, L'Abbate A, Bedini R. Cardiac changes induced by immersion and breath-hold diving in humans. J Appl Physiol 106: 293-297, 2009. First published May 8, 2008 doi:10.1152/japplphysiol.00126.2008.-To evaluate the separate cardiovascular response to body immersion and increased environmental pressure during diving, 12 healthy male subjects (mean age 35.2 Ϯ 6.5 yr) underwent two-dimensional Doppler echocardiography in five different conditions: out of water (basal); head-out immersion while breathing (condition A); fully immersed at the surface while breathing (condition B) and breath holding (condition C); and breath-hold diving at 5-m depth (condition D). Heart rate, left ventricular volumes, stroke volume, and cardiac output were obtained by underwater echocardiography. Early (E) and late (A) transmitral flow velocities, their ratio (E/A), and deceleration time of E (DTE) were also obtained from pulsed-wave Doppler, as left ventricular diastolic function indexes. The experimental protocol induced significant reductions in left ventricular volumes, left ventricular stroke volume (P Ͻ 0.05), cardiac output (P Ͻ 0.001), and heart rate (P Ͻ 0.05). A significant increase in E peak (P Ͻ 0.01) and E/A (P Ͻ 0.01) and a significant reduction of DTE (P Ͻ 0.01) were also observed. Changes occurring during diving (condition D) accounted for most of the changes observed in the experimental series. In particular, cardiac output at condition D was significantly lower compared with each of the other experimental conditions, E/A was significantly higher during condition D than in conditions A and C. Finally, DTE was significantly shorter at condition D than in basal and condition C. This study confirms a reduction of cardiac output in diving humans. Since most of the changes were observed during diving, the increased environmental pressure seems responsible for this hemodynamic rearrangement. Left ventricular diastolic function changes suggest a constrictive effect on the heart, possibly accounting for cardiac output reduction. diving response; hemodynamics PREVIOUS STUDIES ON NATURAL divers (mainly marine mammals) showed that breath-hold diving is associated with energy-saving cardiovascular changes, i.e., a marked reduction in cardiac output [due to the reduction of both stroke volume and heart rate (HR)] and the redistribution of blood flow away from skin and myoglobin-rich muscles in favor of brain and heart (7,28,30). For years, however, technical difficulties have prevented a comprehensive assessment of cardiovascular changes during breath-hold diving in humans. Most of the knowledge on human diving physiology has been obtained from the study of head-out immersed subjects (9, 27), or extrapolated from the results obtained in breath-holding subjects, either with or without face immersion (2, 8, 10). The recent wide diffusion of recreational and competitive breath-hold diving (with a progressive increase of attained depths) highlighted the presence of serious divingrelated patholo...

To investigate the seasonal influences on various arterial blood pressure measurements, 22 subjects in the high normal to mild hypertensive range were examined twice following the same protocol. In one group (13 subjects), measurements were first done in warm conditions and repeated 5-7 months later in cold conditions; in the second group (nine subjects) a reverse sequence was followed. Blood pressure was measured under casual conditions during a hand grip exercise test, mental arithmetic test, and submaximal multistage bicycle exercise test; during the following 24 hours, blood pressure was measured serially with a noninvasive ambulatory blood pressure recorder. Daily outdoor maximum and indoor laboratory temperatures were also obtained. In the cold season, significantly higher values (on the average by 5 -10 mm Hg, /7<0.01) were obtained in both groups for mean diastolic daytime blood pressure. For other measurements, a trend toward higher values in the cold season was observed in both groups, although statistical significance was not obtained in all instances. For nighttime measurements, irrespective of the seasonal sequence, lower values were observed in the second session. Significant correlations were found between the differences in the average daytime ambulatory blood pressures and the corresponding changes of daily maximum outdoor temperatures after 5-7 months. These observations indicate that arterial blood pressure may be strongly influenced by environmental temperature. This phenomenon should be taken into account both in the evaluation of the individual hypertensive patients and in the design and analysis of studies on arterial hypertension, especially when ambulatory blood pressure techniques are employed. {Hypertension 1989; 14:22-27) T hat hypertensive patients often need less pharmacological treatment in summer than in winter is a common experience in clinical practice. In fact, a definite seasonal influence on arterial blood pressure (with values during the winter higher by 2-10 mm Hg than in the summer) has been demonstrated by various studies based on single or repeated measurements that were obtained by a standard sphygmomanometer and by a recent study in children whose blood pressure measurements were taken with an automatic recorder.

In arterial hypertension, MBF during pacing tachycardia and after dipyridamole is impaired. Successful therapy with verapamil increases MBF response to these stimuli, independent of changes in perfusion pressure and left ventricular mass. These results suggest that verapamil directly improves coronary microcirculatory function in hypertension. Enalapril does not significantly change MBF but reduces the inhomogeneity of regional flow distribution.

This study documents that shallow-depth SCUBA diving induces LV enlargement and diastolic dysfunction. Direct underwater evaluation by Doppler echocardiography could be an appropriate tool for unmasking subjects at risk for underwater-related accidents.