Amit J. Shah

Improvements in early mortality and coagulopathy are sustained better in patients with blunt trauma after institution of a massive transfusion protocol in a civilian level I trauma center.

INTRODUCTION Transfusion practices across the country are changing with aggressive use of plasma (fresh-frozen plasma [FFP]) and platelets during massive transfusion with current military recommendations to use component therapy at a 1:1:1 ratio of packed red blood cells to FFP to platelets. METHODS A massive transfusion protocol (MTP) was designed to achieve a packed red blood cell:FFP:platelet ratio of 1:1:1 We prospectively gathered demographic, transfusion, and patient outcome data during the first year of the MTP and compared this with a similar cohort of injured patients (pre-MTP) receiving > or = 10 red blood cell (RBC) in the first 24 hours of hospitalization before instituting the MTP. RESULTS One hundred sixteen MTP activations occurred. Twelve non-trauma patients and 31 who did not receive 10 RBC (15 deaths, 16 early bleeding controls) were excluded. Seventy-three MTP patients were compared with 84 patients with pre-MTP who had similar demographics and injury severity score (29 vs. 29, p = 0.99). MTP patients received an average of 23.7 RBC and 15.6 FFP transfusions compared with 22.8 RBC (p = 0.67) and 7.6 FFP (p < 0.001) transfusions in pre-MTP patients. Early crystalloid usage dropped from 9.4 L (pre-MTP) to 6.9 L (MTP) (p = 0.006). Overall patient mortality was markedly improved at 24 hours, from 36% in the pre-MTP group to 17% in the MTP group (p = 0.008) and at 30 days (34% mortality MTP group vs. 55% mortality in pre-MTP group, p = 0.04). Blunt trauma survival improvements were more marked and more sustained than victims of penetrating trauma. Early deaths from coagulopathic bleeding occurred in 4 of 13 patients in the MTP group vs. 21 of 31 patients in the pre-MTP group (p = 0.023). CONCLUSIONS In the civilian setting, aggressive use of FFP and platelets drastically reduces 24-hour mortality and early coagulopathy in patients with trauma. Reduction in 30 day mortality was only seen after blunt trauma in this small subset.

Post-traumatic stress disorder and incidence of coronary heart disease: a twin study.

OBJECTIVES The aim of this study was to determine whether post-traumatic stress disorder (PTSD) is associated with coronary heart disease (CHD) using a prospective twin study design and objective measures of CHD. BACKGROUND It has long been hypothesized that PTSD increases the risk of CHD, but empirical evidence using objective measures is limited. METHODS We conducted a prospective study of middle-aged male twins from the Vietnam Era Twin Registry. Among twin pairs without self-reported CHD at baseline, we selected pairs discordant for a lifetime history of PTSD, pairs discordant for a lifetime history of major depression, and pairs without either condition. All underwent a clinic visit after a median follow-up of 13 years. Outcomes included clinical events (myocardial infarction, other hospitalizations for CHD and coronary revascularization) and quantitative measures of myocardial perfusion by [(13)N] ammonia positron emission tomography, including a stress total severity score and coronary flow reserve. RESULTS A total of 562 twins (281 pairs) with a mean age of 42.6 years at baseline were included in this study. The incidence of CHD was more than double in twins with PTSD (22.6%) than in those without PTSD (8.9%; p < 0.001). The association remained robust after adjusting for lifestyle factors, other risk factors for CHD, and major depression (odds ratio: 2.2; 95% confidence interval: 1.2 to 4.1). Stress total severity score was significantly higher (+95%, p = 0.001) and coronary flow reserve was lower (-0.21, p = 0.02) in twins with PTSD than in those without PTSD, denoting worse myocardial perfusion. Associations were only mildly attenuated in 117 twin pairs discordant for PTSD. CONCLUSIONS Among Vietnam-era veterans, PTSD is a risk factor for CHD.

Posttraumatic stress disorder and impaired autonomic modulation in male twins

BACKGROUND Posttraumatic stress disorder (PTSD) has been linked to increased morbidity. An inflexibility of the autonomic nervous system might be the underlying mechanism. We aimed to assess whether PTSD and combat trauma exposure are associated with lower heart rate variability (HRV), a measure of autonomic function and a predictor of death. METHODS We measured HRV by power spectral analysis on 24-hour ambulatory electrocardiogram in 459 middle-aged veteran male twins. Combat trauma was assessed with the combat exposure scale, and current and remitted PTSD was assessed with the Structured Clinical Interview for Psychiatry Disorders. Mixed-effects regression models were used to test associations of PTSD and HRV between and within twin pairs. RESULTS Of all twins, 211 had combat exposure, 31 had current PTSD, and 43 had remitted PTSD. Current PTSD was inversely associated with very-low-frequency and low-frequency HRV both in individual twins and within 20 pairs discordant for current PTSD. Twins with current PTSD had a 49% lower low-frequency HRV than their brothers without PTSD (p<.001). Remitted PTSD was not associated with HRV. Results were robust to adjustment for depression and other risk factors. Combat exposure was inversely associated with most HRV frequencies, but this association mostly diminished after adjustment for current PTSD. CONCLUSION In middle-aged veteran men, combat exposure and current PTSD are associated with measures of autonomic inflexibility previously shown to have prognostic significance. The negative health impact of combat exposure on autonomic function is mediated largely through PTSD and might reverse with remission of PTSD.

Depression and History of Attempted Suicide as Risk Factors for Heart Disease Mortality in Young Individuals

CONTEXT Although depression is associated with increased cardiovascular morbidity and mortality, there is virtually no information on whether it also increases the risk in young populations. OBJECTIVES We sought to determine the association of unipolar and bipolar depression and a history of attempted suicide with mortality due to ischemic heart disease (IHD) and cardiovascular disease (CVD) in young US adults and to examine potential sex differences. DESIGN Longitudinal epidemiologic study. SETTING Nationally representative sample of US adults. PARTICIPANTS A total of 7641 US adults aged 17 to 39 years from the 1988-1994 Third National Health and Nutrition Examination Survey. MAIN OUTCOME MEASURES Cardiovascular disease and IHD mortality. Unipolar/bipolar depression and a history of attempted suicide were assessed via the Diagnostic Interview Schedule. RESULTS After a median follow-up of 14.9 years, a total of 51 subjects (0.67%) died of CVD causes and 28 (0.37%) died of IHD. Depression (538 individuals [7.04%]) and history of attempted suicide (419 [5.48%]) were each associated with an increased risk of IHD death, with adjusted hazard ratios of 3.70 (95% CI, 1.32-10.35) for depression and 7.12 (2.67-18.98) for a history of attempted suicide. Women with depression or a history of attempted suicide had a 3-fold adjusted risk of CVD (adjusted hazard ratio, 3.20 [95% CI, 1.12-9.17]) and a 14-fold adjusted risk of IHD (14.57 [2.65-80.10]). Corresponding figures for men were 2.37 (0.85-6.58) and 3.52 (1.05-11.76). CONCLUSION In adults younger than 40 years, depression and history of attempted suicide are significant independent predictors of premature CVD and IHD mortality in both sexes.

Sex differences in mental stress-induced myocardial ischemia in young survivors of an acute myocardial infarction.

Objectives Emotional stress may disproportionally affect young women with ischemic heart disease. We sought to examine whether mental stress–induced myocardial ischemia (MSIMI), but not exercise-induced ischemia, is more common in young women with previous myocardial infarction (MI) than in men. Methods We studied 98 post-MI patients (49 women and 49 men) aged 38 to 60 years. Women and men were matched for age, MI type, and months since MI. Patients underwent technetium-99m sestamibi perfusion imaging at rest, after mental stress, and after exercise/pharmacological stress. Perfusion defect scores were obtained with observer-independent software. A summed difference score (SDS), the difference between stress and rest scores, was used to quantify ischemia under both stress conditions. Results Women 50 years or younger, but not older women, showed a more adverse psychosocial profile than did age-matched men but did not differ for conventional risk factors and tended to have less angiographic coronary artery disease. Compared with age-matched men, women 50 years or younger exhibited a higher SDS with mental stress (3.1 versus 1.5, p = .029) and had twice the rate of MSIMI (SDS ≥3; 52% versus 25%), whereas ischemia with physical stress did not differ (36% versus 25%). In older patients, there were no sex differences in MSIMI. The higher prevalence of MSIMI in young women persisted when adjusting for sociodemographic and life-style factors, coronary artery disease severity, and depression. Conclusions MSIMI post-MI is more common in women 50 years or younger compared with age-matched men. These sex differences are not observed in post-MI patients who are older than 50 years.

Sex and Age Differences in the Association of Depression With Obstructive Coronary Artery Disease and Adverse Cardiovascular Events

Background Young women with coronary heart disease have high rates of depression and a higher risk of adverse events than men of similar age. Whether depression has a higher prognostic value in this group than in men and older women is not known. Our objective was to assess whether depression in young women is associated with higher risk of coronary artery disease (CAD) and adverse outcomes compared with similarly aged men and older women. Methods and Results We examined 3237 patients undergoing coronary angiography for evaluation of CAD and followed them for 2.9 years (median). Depressive symptoms were assessed with the Patient Health Questionnaire (PHQ)‐9, and CAD burden was dichotomized based on its presence or absence. After multivariable adjustment for CAD risk factors, depressive symptoms predicted CAD presence in women aged ≤55 years (odds ratio=1.07 95% confidence interval [CI] 1.02 to 1.13 per 1 point increase in PHQ‐9 score), but not in men aged ≤55 years or women aged >55 years. Depressive symptoms also predicted increased risk of death in women aged ≤55 years (adjusted hazard ratio=1.07, 95% CI 1.02 to 1.14, per 1 point increase in PHQ‐9 score), but not in men aged ≤55 years and women aged >55 years, with P=0.02 for the depression‐sex interaction and P=0.02 for depression‐sex‐age interaction. Conclusions Among patients with suspected or established CAD, depressive symptoms are associated with increased risk of death, particularly in young women. This group may be especially vulnerable to the adverse cardiovascular effects of depression.

Is heart rate variability related to memory performance in middle-aged men?

Objective: Heart rate variability (HRV), a measure of autonomic function, has been associated with cognitive function, but studies are conflicting. Previous studies have also not controlled for familial and genetic influences. Methods: We performed power spectral analysis on 24-hour ambulatory ECGs in 416 middle-aged male twins from the Vietnam Era Twin Registry. Memory and learning were measured by verbal and visual Selective Reminding Tests (SRTs). Mixed-effect regression models were used to calculate associations between and within twin pairs, while adjusting for covariates. Results: The mean age (standard deviation) was 55 (2.9) years. A statistically significant positive association was found between measures of HRV and verbal, but not visual, SRT scores. The most statistically significant unadjusted association was found between very low frequency HRV and verbal total recall SRT, such that each logarithm of increase in very low frequency was associated with an increased verbal SRT score of 4.85 points (p =.002). The association persisted despite the adjustment for demographic and cardiovascular risk factors, and after accounting for familial and genetic factors by comparing twins within pairs. A significant interaction was found between posttraumatic stress disorder (PTSD) and HRV, such that total power and ultra low frequency were associated with SRT in twins (n = 362) without PTSD, but not in those with PTSD. Conclusions: Lower frequency spectra of HRV are associated with verbal, but not visual, learning and memory, particularly in subjects without PTSD. This association may indicate that autonomic c decline.ECG = electrocardiogram; HRV = heart rate variability; SD = standard deviation; SRT = selective reminding test

Effect of Electrocardiographic P-Wave Axis on Mortality

Although P-wave axis is routinely reported on the printouts of most contemporary electrocardiograms, the prognostic significance of its abnormality has not been systematically evaluated. We examined the association between abnormal P-wave axis and cardiovascular and all-cause mortality in 7,501 participants (53% women, mean age 59 years) from the United States Third National Health and Nutrition Examination Survey. P-wave axis of 0° to 75° was considered normal. Participants were linked to the National Death Index to identify the underlying cause of death listed on the death certificates using the International Classification of Disease. During a median follow-up of 13.8 years, a total of 2,541 deaths occurred; of which 1,077 were due to a cardiovascular cause. Abnormal P-wave axis was associated with 55% increased risk of all-cause mortality (hazard ratio [HR] 1.55, 95% confidence interval [CI] 1.43 to 1.69, p <0.01) and 41% increased risk of cardiovascular mortality (HR 1.41, 95% CI 1.24 to 1.62, p <0.01). After adjustment for age, gender, race/ethnicity, diabetes, systolic blood pressure, body mass index, smoking status, total/high-density lipoprotein cholesterol ratio, previous cardiovascular disease, chronic obstructive pulmonary disease, bronchial asthma, heart rate, and use of antiarrhythmic or atrioventricular nodal blocking drugs, the risk of mortality remained significantly high (HR 1.24 95% CI 1.13 to 1.36, p <0.01 for all-cause mortality and HR 1.19 95% CI 1.03 to 1.38, p = 0.02 for cardiovascular mortality) and was consistent across several subgroups of the participants. In conclusion, abnormal P-wave axis is associated with an increased risk of death, findings that call for attention to this routinely reported finding on contemporary electrocardiographic machines.

Laser lead extraction to facilitate cardiac implantable electronic device upgrade and revision in the presence of central venous obstruction

Aims The number of procedures involving upgrade or revision of cardiac implantable electronic devices (CIEDs) is increasing and the risks of adding additional leads are significant. Central venous occlusion in patients with pre-existing devices is often asymptomatic and optimal management of such patients in need of device revision/upgrade is not clear. We sought to assess our use of laser lead extraction in overcoming venous obstruction. Methods and results Patients in need of device upgrade/revision underwent pre-procedure venography to assess venous patency. In patients with venous occlusion or stenosis severe enough to preclude passage of a hydrophilic guide wire, laser lead extraction with retention of the outer sheath in the vasculature was performed with the aim of maintaining a patent channel through which new leads could be implanted. Data were recorded on a dedicated database and patient outcomes were assessed. Between July 2004 and April 2012, laser lead extractions were performed in 71 patients scheduled for device upgrade/revision who had occluded or functionally obstructed venous anatomy. New leads were successfully implanted across the obstruction in 67 (94%) cases. There were two major complications (infection) and four minor complications with no peri-procedural mortality. Device follow-up was satisfactory in 65 (92%) cases with mean follow-up up to 26 ± 19 months. Conclusion Laser lead extraction is a safe and effective option when managing patients with central venous obstruction in need of CIED revision or upgrade.

Sex Differences in Mental Stress‐Induced Myocardial Ischemia in Patients With Coronary Heart Disease

Background Emerging data suggest that young women with coronary heart disease (CHD) are disproportionally vulnerable to the adverse cardiovascular effects of psychological stress. We hypothesized that younger, but not older, women with stable CHD are more likely than their male peers to develop mental stress‐induced myocardial ischemia (MSIMI). Methods and Results We studied 686 patients (191 women) with stable coronary heart disease (CHD). Patients underwent 99mTc‐sestamibi myocardial perfusion imaging at rest and with both mental (speech task) and conventional (exercise/pharmacological) stress testing. We compared quantitative (by automated software) and visual parameters of inducible ischemia between women and men and assessed age as an effect modifier. Women had a more‐adverse psychosocial profile than men whereas there were few differences in medical history and CHD risk factors. Both quantitative and visual indicators of ischemia with mental stress were disproportionally larger in younger women. For each 10 years of decreasing age, the total reversibility severity score with mental stress was 9.6 incremental points higher (interaction, P<0.001) and the incidence of MSIMI was 82.6% higher (interaction, P=0.004) in women than in men. Incidence of MSIMI in women ≤50 years was almost 4‐fold higher than in men of similar age and older patients. These results persisted when adjusting for sociodemographic and medical risk factors, psychosocial factors, and medications. There were no significant sex differences in inducible ischemia with conventional stress. Conclusions Young women with stable CHD are susceptible to MSIMI, which could play a role in the prognosis of this group.