Useful indices of thrombogenesis in the exclusion of intra-cardiac thrombus.

BACKGROUND: Cardioversion in patients with atrial fibrillation (AF) can cause cardioembolic stroke, and effective clinical management is necessary to reduce morbidity and mortality. Currently, transesophageal echocardiography (TEE) is the accepted standard to diagnose cardiogenic thromboemboli; however, a negative TEE does not eliminate the possibility of left atrial thrombus. The objective of this study was to evaluate the diagnostic value of supplementing the TEE with additional noninvasive markers to ensure thrombus absence. METHODS: A prospective study was conducted on 59 patients who underwent TEE for suspected intra-cardiac thrombi. The TEE indications included acute ischemic stroke (45.7%) and AF or flutter (59.3%). D-dimer level and white blood cell counts were assessed. RESULTS: A negative D-dimer level (<200 ng/mL) excluded the presence of intra-cardiac thrombi. Groups with either negative (n = 14) or positive (n = 45) D-dimer levels had comparable clinical characteristics. Comparing positive D-dimer-level patients with thrombus (n = 7) and without thrombus (n = 33), patients with thrombus had reduced left atrial appendage (LAA) velocity (P = .0024), reduced left ventricular ejection fraction (LVEF) (P = .0263), increased neutrophil percent (P = .0261), decreased lymphocyte percent (P = .0216), and increased monocyte counts (P = .0220). The area under the receiver operating characteristic (ROC) curve for thrombus diagnostics was larger for combinations of clinical and biochemical data than for each parameter individually. CONCLUSIONS: Supplementing the gold standard TEE with the analysis of LAA velocity, noninvasive LVEF, D-dimer, and hemostatic markers provided additional useful diagnostic information. Larger studies are needed to further validate the efficacy of supplementing the TEE to better assess patients for intra-cardiac thrombi.

Can α-lipoic acid mitigate progression of aging-related decline caused by oxidative stress?

Aging is progressively deteriorating physiological function that leads to increasing risks of illness and death. Increases in life expectancy and the aging of a large segment of the population have made age-related disability and morbidity increasingly important issues. Supplements such as α-lipoic acid may have antiaging effects by positively affecting oxidative stress, cognitive function, and cardiovascular function.

Value of D-Dimer in Risk Stratification for Thromboembolism in Patients With Atrial Fibrillation and Low CHA2DS2-VASc Score.

Atrial fibrillation (AF) can cause thrombi formation and subsequent emboli deposition in systemic arteries, leading to various organ ischemia and infarction. Anticoagulation therapy can reduce the risk of thrombus formation and embolization, and is initiated based on a patient's risk score, which is frequently estimated with the CHA2DS2-VASc score. We present a case of thromboembolism (TE) where a low CHA2DS2-VASc score suggested a low-moderate risk of systemic embolization, but an elevated plasma D-dimer value prompted further investigation which revealed an intracardiac thrombus with renal embolism. The patient is a 63-year-old male with past medical history of hypertension and AF treated with ablation 2 years prior presenting with sharp right flank pain of 5-hour duration. Primary workup and imaging were unrevealing at the time, and a low CHA2DS2-VASc score was suggestive of aspirin therapy. However, an elevated D-dimer of 289 ng/mL and a transient increase in creatinine pointed to possible etiology of embolic origin. The diagnosis was confirmed with computed tomography (CT) with contrast and transesophageal echocardiogram, revealing renal infarcts and the source of the emboli, respectively. The patient was treated with heparin and transitioned to apixaban prior to discharge with full resolution of symptoms. Through this case, we wish to show D-dimer's predictive value of TE, as well as its potential benefit in risk assessment in patients with AF.

Diastolic filling parameters derived from myocardial perfusion imaging can predict left ventricular end-diastolic pressure at subsequent cardiac catheterization.

UNLABELLED: Morbidity and mortality increase when diastolic dysfunction accompanies coronary artery disease (CAD). An elevated stress (201)Tl lung-to-heart ratio (LHR) is a traditional marker of elevated left ventricular end-diastolic pressure (LVEDP), which adds prognostic value in CAD. Since the introduction of (99m)Tc-labeled agents, this valuable marker has been lost. Hence, there is only a limited ability to assess diastolic dysfunction by myocardial perfusion imaging (MPI). METHODS: Fifty-two consecutive patients with an ejection fraction of >or=45% underwent MPI and cardiac catheterization within 15 d. Peak filling rate (PFR), time to PFR (TPFR), and filling rate during the first third of diastole (1/3FR) were obtained from MPI with SPECT software. Resting (201)Tl LHR was calculated manually, and LVEDP was obtained at catheterization. RESULTS: PFR, TPFR, and 1/3FR correlated significantly with LVEDP (r= -0.53, 0.45, and -0.45, respectively; P=0.00005, 0.0009, and 0.0009, respectively), whereas resting (201)Tl LHR did not (r=0.10, P=0.49). Receiver-operating-characteristic curve analysis of PFR, TPFR, and 1/3FR for detecting LVEDPs of >or=18 mm Hg showed areas under the curve of 0.83, 0.75, and 0.80, respectively. The combination of PFR and 1/3FR showed a negative predictive value of 84%, a positive predictive value of 86%, and a specificity of 94%. CONCLUSION: Diastolic filling variables obtained with the SPECT software showed a significant correlation with LVEDP. PFR, TPFR, and 1/3FR were superior to resting (201)Tl LHR and showed good sensitivity, specificity, and predictive power for detecting LVEDPs of >or=18 mm Hg. Hence, combining data on the presence of perfusion defects with data on diastolic impairments can be achieved by adding these variables to MPI results.

Angina, an unusual and late complication of the Cabrol procedure: a case report and review of the literature.

Several techniques exist for surgical reimplantation of the coronary arteries to a composite aortic graft for repair of the ascending aorta. The Cabrol graft is an attachment of a Dacron tube between the coronary arteries and the composite aortic graft in aortic root replacement. Very late presentation of myocardial ischemia related to the Cabrol conduit graft is exceedingly rare. We report a rare and late development of angina due to a dysfunctional Cabrol conduit, which was successfully cured with coronary bypass grafting. Knowledge of this technique is vital for the accurate interpretation of coronary angiograms and CT scan findings and crucial for the treatment planning in patients who have had previous implantation of the Cabrol graft.

Encircling reperfusion pattern on the stress-minus-delay bull's-eye map improves sensitivity of myocardial perfusion scans.

BACKGROUND: Myocardial perfusion imaging is subject to considerable noise due to re-registration and attenuation artifact. METHODS: On a retrospective review, we identified 51 studies that showed encircling reperfusion pattern on a stress-minus-delay bull's-eye map with concurrent cardiac catheterization within 4 months. Encircling reperfusion was defined as a band of reversibility > or =2.5 standard deviations above that of the gender-matched and age-matched normal studies. This had to surround the delay defect for at least two-thirds of its circumference on the stress-minus-delay bull's-eye map. Three expert readers, blinded to cardiac catheterization results, individually interpreted myocardial perfusion imaging without and with a stress-minus-delay bull's-eye map. A certainty index of 1-100 (100 being the highest certainty for the presence of perfusion defects) was recorded for image interpretation. RESULTS: The intra-class correlation coefficient between readers indicated a strong agreement. Using encircling reperfusion pattern on a stress-minus-delay bull's-eye map, the mean increase in certainty index scores was 8.0+/-7.30 (P<0.0001). This increase in certainty index scores was associated with a significant increase in sensitivity from 67 to 83% (P=0.01) without any significant decrease in specificity (P=0.16). CONCLUSIONS: The pattern of encircling reperfusion on the stress-minus-delay bull's-eye map can improve the interpreter's confidence and sensitivity without significantly compromising specificity for identifying true myocardial perfusion defects.

Latex D-dimer signal in in situ femoral vein thrombus in swine and effect of minidose exogenous tissue plasminogen activator bolus.

STUDY OBJECTIVES: We created in situ femoral vein thrombi in swine to investigate the response of the latex d-dimer signal to acute in situ venous thrombosis, and to determine the minimum dose of exogenous bolus tissue plasminogen activator (t-PA) required to significantly elevate the d-dimer signal. STUDY DESIGN: We studied seven swine (20 to 22 kg) under pentobarbital anesthesia. A 6-cm segment of the proximal femoral vein was surgically exposed and briefly ligated. Thrombin, 250 U, was then injected into the isolated femoral vein segment to create an in situ clot. After clot formation was documented to be complete between the ligatures, they were then released. D-dimer levels were then measured every 15 min for 1 h before and 1 h after clot formation with ligatures released. Time-response curves to establish timing of peak t-PA effect were performed, and then escalating dose-response curves of d-dimer level to minidose t-PA were plotted. RESULTS: After formation of the clot, the release of ligatures resulted in no change in d-dimer levels over 1 h (p = 0.62) in all swine. When a time-response curve to exogenous t-PA bolus in the presence of femoral clot was plotted, there was a maximal increase in d-dimer signal at 30 min after bolus t-PA administration. The subsequent dose-response curves for escalating fivefold boluses of minidose t-PA showed an increase in d-dimer signal at doses of 0.8 mg (p = 0.03) and 4 mg (p = 0.003). CONCLUSION: We conclude the following: (1) in situ femoral vein clot formation does not elevate d-dimer signal for 1 h after ligature release; (2) minidose t-PA boluses of 0.8 mg and 4 mg significantly elevated the latex d-dimer signal above baseline; and (3) there is a potential role of minidose t-PA in enhancing the d-dimer signal in in situ deep venous thrombosis.

Effects of acute volume loading and hemorrhage on intestinal vascular capacitance: a mechanism whereby capacitance modulates cardiac output.

BACKGROUND: Changes in intestinal vascular capacitance during acute volume loading and hemorrhage have not been described. OBJECTIVES: To determine the effects of volume loading and hemorrhage on the intestinal vascular pressure-volume relationship and cardiac output. PATIENTS AND METHODS: In 11 alpha-chloralose-anesthetized dogs, a pneumatic portal venous constrictor and catheter were positioned to increase and measure portal venous pressure (Ppv), respectively. Relative changes in intestinal blood volume (IBV) were determined by blood-pool scintigraphy and expressed as the percentage change from control values (taken as 100%). Ppv-IBV relationships were constructed by graded portal vein constriction. RESULTS: IBV and cardiac output increased by 60 6% and 178 48%, respectively, and Ppv increased from 5.8 0.9 mmHg to 13.2 1.8 mmHg after initial volume loading (40 mL/kg of an isotonic glucose-saline solution over 7 min). IBV gradually decreased and reached near-control values after 75 min. In seven dogs, hemorrhage (sufficient to decrease mean aortic pressure by 56 4%) decreased IBV and cardiac output to 88 4% and 52 3% of control values, respectively, and Ppv decreased to 3.2 0.8 mmHg. CONCLUSIONS: A sigmoid function curve defined the relationship between cardiac output and IBV. Cardiac output remained constant over a wide range (between approximately 95% and 135% of control IBV). Outside this range, insufficient dilation or constriction resulted in a marked increase or decrease in venous pressures and cardiac output. These data indicate that vasculature capacitance modulates cardiac output during acute volume loading and hemorrhage, thereby maintaining cardiac output relatively constant over a wide range of total vascular blood volume.

Brain natriuretic hormone predicts stress-induced alterations in diastolic function.

BACKGROUND: Mental stress (MS) reduces diastolic function (DF) and may lead to congestive heart failure with preserved systolic function. Whether brain natriuretic hormone (brain natriuretic peptide [BNP]) mediates the relationship of MS with DF is unknown. METHODS: One hundred sixty individuals aged 30 to 50 years underwent 2-hour protocol of 40-minute rest, videogame stressor and recovery. Hemodynamics, pro-BNP samples and DF indices were obtained throughout the protocol. Separate regression analyses were conducted using rest and stress E/A, E' and E/E' as dependent variables. Predictor variables were entered into the stepwise regression models in a hierarchical fashion. At the first level, age, sex, race, height, body mass index, pro-BNP and left ventricular mass (LVM) were permitted to enter the models. The second level consisted of systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate (HR). The final level contained cross-product terms of race by SBP, DBP and HR. RESULTS: E/A ratio was lower during stress compared to rest and recovery (P < 0.01). Resting E/A ratio was predicted by a regression model of age (-0.31), pro-BNP (0.16), HR (-0.40) and DBP (-0.23) with an R² = 0.33. Stress E/A ratio was predicted by age (-0.24), pro-BNP (0.08), HR (-0.38) and SBP (-0.21) with total R² = 0.22. Resting E' model consisted of age (-0.22), pro-BNP (0.26), DBP (-0.27) and LVM (-0.15) with an R² = 0.29. Stress E' was predicted by age (-0.18), pro-BNP (0.35) and LVM (-0.18) with an R² = 0.18. Resting E/E' was predicted by race (0.17, B > W) and DBP (0.24) with an R² = 0.10. Stress E/E' consisted of pro-BNP (-0.36), height (-0.26) and HR (-0.21) with an R² = 0.15. CONCLUSIONS: pro-BNP predicts both resting and stress DF, suggesting that lower BNP during MS may be a marker of diastolic dysfunction in apparently healthy individuals.

Embolic Stroke Diagnosed by Elevated D-Dimer in a Patient With Negative TEE for Cardioembolic Source.

We report a case of cerebrovascular accident with thromboembolic stroke etiology in a patient who had atrial flutter and negative transesophageal echocardiography (TEE) results. The increased D-dimer levels (1877 ng/mL) initiated referral for magnetic resonance imaging and magnetic resonance angiography of the brain that showed classic recanalization of an embolic thrombus in the angular branch of the left middle cerebral distribution. The D-dimer level of this patient was normalized after 3 months of anticoagulation therapy. Although TEE is considered the gold standard for evaluation of cardiac source of embolism, exclusion of intracardiac thrombus with TEE alone does not eliminate the risk of thromboembolic events. This case highlights the utility of D-dimer as a potential adjunct in the decision-making process to guide investigation of thromboembolism, determine subsequent therapy, and hence reduce the risk of embolic stroke recurrence.

The D-dimer assay: a possible tool in the evaluation of atrial thrombosis.

Atrial fibrillation (AF) is a common arrhythmia seen in clinical practice, and affects more than 4% of the population older than 60 years of age. Peripheral thromboembolism contributes significantly to the observed morbidity and mortality. Symptomatic AF, before cardioversion to normal sinus rhythm, requires either exclusion of atrial thrombi using transesophageal echocardiography (TEE) or the conventional use of three weeks of adequate anticoagulation. The exclusion of atrial thrombi by TEE, a nontomographic technique but comparable with conventional treatment of AF in outcomes, has inherent limitations due to the complex three-dimensional multilobed anatomy of the left atrial appendage, where the majority of atrial thrombi arise. Also, the conventional treatment of three weeks of therapeutic anticoagulation before cardioversion reportedly does not always eliminate atrial thrombi. Plasma D-dimer constitutes an antigen-antibody reaction to the dimeric final degradation product of a mature clot. An elevated fibrin D-dimer has a high sensitivity for intravascular thrombosis and, hence, may improve the evaluation of a patient with AF before cardioversion in addition to a TEE. A case is presented in which a positive D-dimer resulted in performing TEE to document atrial thrombosis and the complications of previous bacterial endocarditis. In the present case, this involved aortic root abscess formation and acute aortic regurgitation because of flailing of the noncoronary cusp that resulted in recurrent pulmonary edema.

Pharmacologic stress myocardial perfusion imaging.

Pharmacologic stress agents (dipyridamole, adenosine and dobutamine) allow virtually all patients to be safely assessed for ischemic heart disease. These agents have mild but significant side effects, mandating a thorough knowledge of indications, contraindications, side effects and management before their use. Adjunctive exercise improves image quality in vasodilator pharmacologic myocardial perfusion imaging. Diabetics, especially women, have a much higher cardiac event rate than nondiabetics for an equal amount of ischemia. They also have a higher incidence of asymptomatic ischemia. There is growing support for screening with myocardial perfusion imaging (MPI) for asymptomatic ischemia in diabetics. The ability of MPI to identify hypocontractile but viable myocardium, thus predicting improvement in myocardial function after revascularization, is one of the most powerful uses of the modality. Vasodilator MPI should be used as the initial test in patients with left bundle branch block or paced ventricular rhythm, even if they are able to exercise.

Characteristics of patients with cervical spinal injury requiring permanent pacemaker implantation.

Acute cervical spinal cord injury frequently results in bradydysrhythmia, which may lead to hypotension and asystole. Such symptoms are more common in the first 2 weeks after the injury. Treatment modalities include atropine, epinephrine, aminophylline, and pacemaker insertion. The criteria for pacemaker use in this population are not well defined. We describe characteristics of 3 patients who required permanent, transvenous pacemaker implantation for recurrent symptoms. In 2 of the 3 patients, transcutaneous pacing failed to provide adequate protection. Transcutaneous pacemakers are not reliable, as was the case of these patients, and early consideration for transvenous pacemaker insertion may be indicated, especially in hemodynamically unstable patients. In this report, all 3 patients required permanent pacemaker implantation.