Is outdoor recreational activity an independent predictor of cardiovascular disease mortality - NHANES III?

BACKGROUND AND AIMS: To investigate if frequency of outdoor recreational activity (ORA) predicts cardiovascular disease (CVD) mortality, independent of serum 25(OH)D concentration. METHODS AND RESULTS: Baseline data on ORA and serum 25(OH)D, collected from 11,746 participants aged 30-90 years in the Third National Health and Nutrition Examination Survey during 1988-1994, were linked to the National Death Index for assessment of CVD deaths from baseline through December 2006. CVD mortality as a primary cause of death was assessed during a mean follow up of 12.9 (SD, 4.2) years. There were 1519 CVD deaths during follow up. A strong positive association was observed between frequency of ORA in the last month and serum 25(OH)D (p < 0.001). Compared to participants who did no ORA in the last month, the hazard ratio (HR) of CVD mortality was 0.72 (95% confidence interval 0.58-0.90) for those doing ORA 1-4 times, 0.64 (0.47-0.89) for 5-12 times, 0.70 (0.56-0.89) for 13-30 times and 0.63 (0.47-0.84) for ≥30 times (p-trend < 0.001), in a Cox proportional hazards regression model which included 25(OH)D and CVD risk factors. Serum 25(OH)D was inversely associated with CVD mortality (p-trend, 0.01) in this same model. CONCLUSIONS: An inverse association between ORA and CVD mortality was observed independent of 25(OH)D. The underlying mechanism for this association may not involve 25(OH)D hence, further studies are warranted to confirm and investigate the underlying mechanism.

Research efforts to control highly pathogenic arenaviruses: a summary of the progress and gaps.

Significant progress has been made in the past 10 years in unraveling the molecular biology of highly pathogenic arenaviruses that are endemic in several West African countries (Lassa fever virus) and in some regions of South America (Argentine and Bolivian hemorrhagic fever viruses). While this has resulted in proof-of-concept studies of novel vaccine candidates in non-human primates and in the discovery of several novel antiviral small molecule drug candidates, none of them has been tested in the clinic to date. The recent Ebola outbreak in West Africa has demonstrated very clearly that there is an urgent need to develop the prophylactic and therapeutic armamentarium against viral hemorrhagic fever viruses as part of a global preparedness for future epidemics. As it pertains to this goal, the present article summarizes the current knowledge of highly pathogenic arenaviruses and identifies opportunities for translational research.

Biphasic and monophasic transthoracic defibrillation in pigs with acute left ventricular dysfunction.

OBJECTIVE: Our purpose was to compare biphasic versus monophasic shock success for VF termination in a porcine model of acute left ventricular (LV) dysfunction. BACKGROUND: For the termination of ventricular fibrillation (VF), transthoracic biphasic waveform shocks achieve higher success rates than monophasic shocks. However, the effectiveness of biphasic versus monophasic defibrillation in a setting of left ventricular dysfunction has not been reported. METHODS: In 23 open-chest adult swine (15-25 kg), LV dysfunction [> or =25% decline in cardiac output (CO)] was induced by continuous inhalation of halothane (1-1.75%). Each pig randomly received transthoracic biphasic and monophasic shocks at three energy levels (30, 50 and 100 J) in two conditions: baseline and LV dysfunction. Halothane effect on left ventricular size and contraction was measured by echocardiography in three additional swine. RESULTS: With halothane, pigs demonstrated a decline in CO (baseline 4.16+/-0.19, halothane 2.72+/-0.19 l/min, P<0.01), mean arterial pressure (baseline 107.2+/-3.5, halothane 80.1+/-3.4 mmHg, P<0.01) and increased left ventricular end-diastolic pressure (baseline 6.4+/-0.9, halothane 12.7+/-0.8 mmHg, P<0.01). LV diameters increased and fractional shortening fell. During baseline, biphasic shocks achieved significantly greater success (termination of VF) compared to monophasic waveforms (100 J: biphasic 83.3+/-9.5 versus monophasic 38.9+/-9.5%, P<0.01; 50 J: biphasic 67.1+/-8.8 versus monophasic 11.8+/-5.7%, P<0.01; 30 J: biphasic: 31.9+/-6.4 versus monophasic 0+/-0%, P<0.01). The superiority of the biphasic waveform to terminate VF was retained during LV dysfunction at all energy levels (100 J: biphasic 78.3+/-7.3 versus monophasic 37.5+/-8.1%, P<0.01; 50 J: biphasic 65.5+/-11.5 versus monophasic 11.7+/-5.9%, P<0.01; 30 J: biphasic: 40.6+/-8.0 versus monophasic 3.1+/-3.1%, P<0.01). Within both waveforms, there were no significant differences in percent shock success at any energy level comparing baseline with LV dysfunction. CONCLUSION: In this porcine model of acute LV dysfunction, biphasic waveform shocks were not only superior to monophasic waveform shocks for termination of VF during baseline, but retained superiority to monophasic waveform shocks when LV dysfunction was present.

Does electrode polarity alter the energy requirements for transthoracic biphasic waveform defibrillation? Experimental studies.

BACKGROUND: Electrode polarity may alter the success of biphasic shocks from implantable systems. Whether the electrode polarity influences the success of transthoracic biphasic defibrillation is unknown. We determined the effect of electrode polarity on biphasic transthoracic defibrillation in a porcine model. METHOD: In ten anesthetized adult pigs, 16-28 kg, electrode pads were placed in two different orientations on the chest wall; apex-right parasternal and sternal-vertebral column. Ventricular fibrillation (VF) was electrically induced and allowed to persist for 30 s. Truncated exponential biphasic shocks (5/3 ms) were delivered at 20, 30, 50, 70 and 100 J. Four shocks at each energy level were delivered to construct energy vs. % success curves for VF termination. Electrode polarity for the first pulse was varied so that the first pulse cathode was either the apex (for apex-parasternal) or sternum (for sternum-vertebral column), or the reverse. The second pulse polarity was always the opposite of the first. RESULTS: VF termination success rose from 0 to 86% as energy increased from 20 to 100 J. Varying the electrode polarity did not alter success rates at any energy level with either electrode pad placement. CONCLUSION: In this porcine model of transthoracic defibrillation, varying the biphasic shock electrode polarity did not alter transthoracic defibrillation success. Positional labeling of transthoracic biphasic defibrillation electrode pads may be unnecessary.

Pediatric transthoracic defibrillation: biphasic versus monophasic waveforms in an experimental model.

OBJECTIVES: The purpose of this study was to determine and compare the efficacy of biphasic and monophasic waveforms in a porcine model of pediatric defibrillation. BACKGROUND: The efficacy and safety of biphasic waveforms in children has not been established. METHODS: We initially studied 27 piglets: 12 weighed 3-6 kg ('infants'), and 15 weighed 7-12 kg ('children'). Ventricular fibrillation (VF) was induced by rapid right ventricular pacing and maintained for 15 s. Transthoracic shocks of 7-100 J energy were given using monophasic (5 ms truncated exponential) and biphasic (5 ms positive, 5 ms negative pulse, truncated exponential) waveforms. A second study of four 'infant' and four 'child' piglets utilized the same protocol but with a 10 ms instead of 5 ms monophasic truncated exponential shock waveform compared with the 10 ms biphasic waveform. RESULTS: For both biphasic and monophasic waveforms, shock success rate (termination of VF) rose steadily as energy was increased. In the first study in the 'infant' 3-6 kg group, the 10 ms biphasic waveforms were superior to 5 ms monophasic waveforms at 10, 20, and 30 J energies, and in the 'child' 7-12 kg group at 20 and 30 J energies (P<0.05). High success rates (>80%) were achieved by 20 J (4 J/kg) biphasic waveform shocks in the 'infant' piglets and 30 J (3 J/kg) biphasic waveform shocks in the 'child' piglets. In the second study using a 10 ms monophasic waveform, we found similar results. Pulseless electrical activity occurred in two animals following biphasic shocks and in two animals following monophasic shocks. CONCLUSIONS: Biphasic waveforms proved superior to monophasic waveforms in both infant and child models. High success rates were achieved with low-energy biphasic shocks. Biphasic waveform defibrillation is a promising advance in pediatric resuscitation.

Nitric oxide synthase inhibitors decrease coronary sinus-free radical concentration and ameliorate myocardial stunning in an ischemia-reperfusion model.

OBJECTIVES: Our objective was to determine the effect of a nitric oxide synthase inhibitor, NG-nitro-L-arginine (L-NNA) on free radical generation and myocardial contractility after ischemia-reperfusion. BACKGROUND: Cardiotoxic free radicals are generated by ischemia-reperfusion sequences. Nitric oxide reacts with superoxide radical to form peroxynitrite, which generates additional free radicals. Our hypothesis was that by inhibiting NO production, free radical formation will be diminished, which should be cardioprotective. METHODS: We studied 32 dogs. Coronary occlusion-reperfusion (20 min each) sequences were created by intracoronary balloon angioplasty inflation-deflation. Using electron paramagnetic resonance, we monitored the coronary sinus concentration of ascorbate free radical (Asc*-), a measure of total oxidative flux. The L-NNA (4.8 mg/kg total) was infused intravenously during occlusion-reperfusion; control dogs received saline. Immunohistochemical staining demonstrated the peroxynitration product nitrotyrosine. RESULTS: In the control dogs Asc*- rose from 3.2 +/- SD 0.5 nmol/l to 4.8 +/- 1.1 nmol/l with reperfusion, a 50% rise. With L-NNA the Asc*- rose from 3.2 +/- 0.9 nmol/l to 4.0 +/- 1.2 nmol/l, a 25% rise (p < 0.01, L-NNA vs. control). Echocardiographic left ventricular fractional area shortening (FAS) in the control dogs declined from 38 +/- 19% (baseline) to 26 +/- 14% (ischemia), and to 22 +/- 11% with reperfusion (p < 0.01 vs. baseline). With L-NNA, FAS declined from 36 +/- 13% (baseline) to 27 +/- 12% (ischemia) but then rose to 33 +/- 14 with reperfusion (p = NS vs. baseline). Nitrotyrosine was present in the myocardium subjected to ischemia-reperfusion, but almost absent in dogs receiving L-NNA. Myocardial perfusion was not altered by L-NNA. CONCLUSIONS: The NO synthase inhibitors decrease coronary sinus free radical concentration and ameliorate myocardial stunning after ischemia-reperfusion.

Intracardiac echocardiography identifies pericardial fluid and can monitor the success of pericardiocentesis: experimental studies.

Pericardial tamponade is a complication of cardiac catheterization. Our purpose was to evaluate the ability of intracardiac echocardiography (ICE) to identify pericardial fluid and the success of pericardiocentesis in an experimental model. Seven dogs were studied with the use of a 10F, 10-MHz ICE catheter in the left ventricle. Normal saline was injected into the pericardial space while heart rate and arterial pressure were continuously monitored. The ability of ICE to identify the presence of pericardial fluid and the maximum pericardial separation and to monitor fluid accumulation and withdrawal was evaluated. Thirteen sequences of saline injection/withdrawal were studied. ICE correctly identified the presence or absence of pericardial fluid in all 13 injection/withdrawal sequences. The average sonolucent space separating epicardium from pericardium was 12 +/- 7 mm, generated from 148 +/- 65 mL of saline and producing a 35 +/- 23 mm Hg decrease in systolic blood pressure. ICE readily identified the accumulation and removal of pericardial fluid in this experimental model and should be an excellent tool to monitor pericardiocentesis in the catheterization laboratory.

Coronary risk area measurement by intracardiac echocardiography and ultrasound contrast.

The perfusion bed of an occluded coronary artery-the coronary risk area-determines infarct size. Our objective was to evaluate the combined techniques of intracardiac echocardiography (ICE) and ultrasound contrast echocardiography for real-time estimation of the coronary risk area in an experimental model. We studied 13 pigs and 2 dogs. The left anterior descending coronary was occluded by inflating coronary balloons. An ultrasound contrast agent was injected either through the dilation catheter (distal to the inflated balloon) directly into the occluded artery to opacify the "positive" risk area or into the aortic root during coronary balloon inflation to determine the nonopacified "negative" risk area. Evans blue dye was injected into the occluded artery to stain the risk area, allowing an independent measurement. The mean left anterior descending negative risk area was 26% +/- 10% of the left ventricular myocardial area, the mean positive risk area was 24% +/- 10%, and the Evans blue-stained risk area was 25% +/- 9%. By Bland-Altman analysis, the positive Optison-Evans blue mean +/- SD difference was 1.42% +/- 6.42%; the negative Optison-Evans blue mean +/- SD difference was 1.02% +/- 7.56%. Coronary risk area can be determined with intracardiac echocardiography and ultrasound contrast.

Familial excess longevity in Utah genealogies.

We evaluated the influence of family history on longevity by examining longevity in a cohort of 78,994 individuals drawn from the Utah Population Database (UPDB) who were born between 1870 and 1907, and lived to at least age 65. We examined Mendelian genetic and social modes of transmission of excess longevity (the difference between observed and expected longevity) by varying weighted kinship contributions over different classes of relatives. The genetic component of the variation in excess longevity measured as heritability, h2, was approximately 0.15 (95% confidence interval [CI] 0.12-0.18). Among siblings of probands who reached the 97th percentile of excess longevity (+ 14.8 years, currently age 95 for men and 97 for women), the relative risk of recurrence (lambdas) was 2.30 (95% CI 2.08-2.56). In sibships whose relatives were in the top 15% of the distribution for familial excess longevity, the value of lambdas increased substantially, indicating that considering the longevity of distant relatives may be helpful in the selection of families in which to identify genes influencing aging and longevity.

Paternal and maternal components of the predisposition to preeclampsia.

BACKGROUND: There is an inherited maternal predisposition to preeclampsia. Whether there is a paternal component, however, is not known. METHODS: We used records of the Utah Population Database to identify 298 men and 237 women born in Utah between 1947 and 1957 whose mothers had had preeclampsia during their pregnancy. For each man and woman in the study group, we identified two matched, unrelated control subjects who were not the products of pregnancies complicated by preeclampsia. We then identified 947 children of the 298 male study subjects and 830 children of the 237 female study subjects who had been born between 1970 and 1992. These children were matched to offspring of the control subjects (1950 offspring of the male control group and 1658 offspring of the female control group). Factors associated with preeclampsia were identified, and odds ratios were calculated with the use of stepwise logistic-regression analysis. RESULTS: In the group whose mothers had had preeclampsia (the male study group), 2.7 percent of the offspring (26 of 947) were born of pregnancies complicated by preeclampsia, as compared with 1.3 percent of the offspring (26 of 1973) in the male control group. In the female study group, 4.7 percent of the pregnancies (39 of 830) were complicated by preeclampsia, as compared with 1.9 percent (32 of 1658) in the female control group. After adjustment for the offspring's year of birth, maternal parity, and the offspring's gestational age at delivery, the odds ratio for an adult whose mother had had preeclampsia having a child who was the product of a pregnancy complicated by preeclampsia was 2.1 (95 percent confidence interval, 1.0 to 4.3; P=0.04) in the male study group and 3.3 (95 percent confidence interval, 1.5 to 7.5; P=0.004) in the female study group. CONCLUSIONS: Both men and women who were the product of a pregnancy complicated by preeclampsia were significantly more likely than control men and women to have a child who was the product of a pregnancy complicated by preeclampsia.

Cerebral embolism resulting from a transvenous pacemaker catheter inadvertently placed in the left ventricle: a report of two cases confirmed by echocardiography.

BACKGROUND: Transvenous pacemaker catheters may be placed unintentionally into the left ventricle. This can lead to thromboembolic complications. METHODS AND RESULTS: We report two cases where pacemaker catheters placed unintentionally in the left ventricle via a patent foramen ovale resulted in cerebrovascular accidents. The malpositioned pacemaker catheters were demonstrated by transthoracic and transesophageal echocardiography. In both patients, no further embolic events have occurred after treatment, which in one case consisted of pacemaker catheter removal and in the other case, anticoagulation. CONCLUSION: Echocardiography can be useful to confirm inadvertent left ventricular pacemaker placement in patients with pacemakers who have cerebrovascular accidents.

Measures of familial aggregation as predictors of breast-cancer risk.

BACKGROUND: Several measures of familial disease aggregation have been proposed, but only a few of these are designed to be implemented at the individual level. We evaluate two of them in the context of breast-cancer incidence. METHODS: A population-based cohort consisting of 114 429 women born between 1874 and 1931 and at risk for breast cancer after 1965 was identified by linking the Utah Population Data Base and the Utah Cancer Registry. Two competing methods were used to obtain predictors of familial aggregation of risk: the number of first-degree relatives with breast cancer (NIST) and the familial standardised incidence ratio (FSIR), which weights the disease status of relatives based on their degree of relatedness with the proband. Relative risks were estimated using Mantel-Haenszel. Poisson regression and spline regression methods. The age-dependent hazard function was also estimated. RESULTS: Compared to a baseline category containing 91.5% of the subjects, the 0.7% of subjects identified as high risk using the FSIR criterion had a relative risk of about 2.8, while those identified as high risk using the NIST criterion had a relative risk of 2.0. Moderate-risk subjects had a relative risk of about 1.75 using either criterion. FSIR was a significant predictor of risk even for those with no affected first-degree relatives. No decline in the baseline risk was observed at advanced ages. CONCLUSIONS: FSIR appears to be a better predictor of breast-cancer risk than NIST, particularly for high-risk subjects.

Interactions between CPR and defibrillation waveforms: effect on resumption of a perfusing rhythm after defibrillation.

BACKGROUND: Cardiopulmonary resuscitation (CPR) improves survival from cardiac arrest. The interactions between CPR and the new biphasic (BiP) defibrillation waveforms have not been defined. Our purpose was to compare the effect of CPR versus no CPR during BiP and damped sinusoidal (DS) shocks on the termination of ventricular fibrillation (VF) and the resumption of a perfusing rhythm. METHODS: We studied 20 pigs; VF was induced electrically and allowed to persist for 6 min. During VF episodes each pig received (in random order): (a) 6 min of full CPR (continuous ventilation and closed chest mechanical compression (Thumper, Michigan Instruments)) followed by DS defibrillation at 100 J; (b) no CPR, DS defibrillation; (c) 6 min of full CPR and BiP defibrillation at 100 J; and (d) no CPR, BiP defibrillation. RESULTS: BiP shocks with CPR terminated VF in 83% of attempts versus 45% without CPR (15/18 and 5/11 respectively, P<0.05). DS shocks with CPR were successful in terminating VF in 53% of attempts; DS shocks without CPR were successful in 44% (8/15 and 7/16, respectively, P=NS). No animal achieved a perfusing rhythm after shocks of either waveform if CPR did not precede the shocks during the 6-min VF period, whereas if CPR was administered during VF 46% (11/24) of the combined BiP/DS shocks restored a perfusing rhythm (P<0.01). CONCLUSION: In this experimental long duration VF model, CPR was essential for a perfusing rhythm after termination of VF by shocks with either waveform. CPR facilitated the termination of VF and resumption of a perfusing rhythm after biphasic waveform defibrillation but not after damped sinusoidal waveform defibrillation.

Effect of shaving the chest of hirsute subjects on transthoracic impedance to self-adhesive defibrillation electrode pads.

We determined transthoracic impedance (TTI) before and after shaving in 9 hirsute and 11 nonhirsute subjects. TTI in hirsute subjects was mean +/- SE 162 +/- 11 versus 103 +/- 6 ohms in nonhirsute subjects (p <0.01); TTI decreased to 105 +/- 3 ohms after shaving the hirsute chests (p <0.01).

Quo vadis? How should we train cardiologists at the turn of the century?

BACKGROUND: Cardiovascular medicine is weathering challenges on multiple fronts, and the paradigm of cardiovascular fellowship training has changed as a result. METHODS AND RESULTS: On the basis of a review of the literature and surveys of former trainees, we have evaluated our Cardiovascular Fellowship Program at the University of Iowa. We have identified principles fundamental to the training of fellows. We extend these principles to propose practical ideas for responding to the challenges we face in the rapidly changing landscape of medicine in a new millennium. CONCLUSIONS: We have proposed a few principles and numerous concrete, practical suggestions that will guide our Cardiovascular Fellowship in the future. These ideas may prove useful to other training programs.

Cardiac hypertrophy is not a required compensatory response to short-term pressure overload.

BACKGROUND: Cardiac hypertrophy is considered a necessary compensatory response to sustained elevations of left ventricular (LV) wall stress. METHODS AND RESULTS: To test this, we inhibited calcineurin with cyclosporine (CsA) in the setting of surgically induced pressure overload in mice and examined in vivo parameters of ventricular volume and function using echocardiography. Normalized heart mass increased 45% by 5 weeks after thoracic aortic banding (TAB; heart weight/body weight, 8.3+/-0.9 mg/g [mean+/-SEM] versus 5. 7+/-0.1 mg/g unbanded, P<0.05). Similar increases were documented in the cell-surface area of isolated LV myocytes. In mice subjected to TAB+CsA treatment, we observed complete inhibition of hypertrophy (heart weight/body weight, 5.2+/-0.3 mg/g at 5 weeks) and myocyte surface area (endocardial and epicardial fractions). The mice tolerated abolition of hypertrophy with no signs of cardiovascular compromise, and 5-week mortality was not different from that of banded mice injected with vehicle (TAB+Veh). Despite abolition of hypertrophy by CsA (LV mass by echo, 83+/-5 mg versus 83+/-2 mg unbanded), chamber size (end-diastolic volume, 33+/-6 microL versus 37+/-1 microL unbanded), and systolic ejection performance (ejection fraction, 97+/-2% versus 97+/-1% unbanded) were normal. LV mass differed significantly in TAB+Veh animals (103+/-5 mg, P<0.05), but chamber volume (end-diastolic volume, 44+/-6 microL), ejection fraction (92+/-2%), and transstenotic pressure gradients (70+/-14 mm Hg in TAB+Veh versus 77+/-11 mm Hg in TAB+CsA) were not different. CONCLUSIONS: In this experimental setting, calcineurin blockade with CsA prevented LV hypertrophy due to pressure overload. TAB mice treated with CsA maintain normal LV size and systolic function.