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.

Rapid decline of resting heart rate trajectories from childhood to young adulthood is paradoxically associated with increased cardiac mass.

BACKGROUND: Little is known about the varied resting heart rate (RHR) trajectory patterns from childhood to young adulthood and their clinical significance. We aim to identify RHR trajectories from childhood to young adulthood, and to determine their relationship with left ventricular mass (LVM) index. METHODS: RHR was measured up to 15 times over a 21-year period in 759 participants from childhood to young adulthood. LVM was measured using echocardiography and was normalised to body surface area to obtain LVM index in 546 participants. RESULTS: Using latent class models, three trajectory groups in RHR from childhood to young adulthood were identified, including high-decreasing group (HDG), moderate-decreasing group (MDG), and low-decreasing group (LDG). We found that trajectory of RHR was a significant predictor of LVM index with faster decrease of RHR associated with higher levels of total peripheral resistance (P for trend <0.001) and LVM index (P for trend <0.001). Compared to the LDG, individuals in the HDG showed higher LVM index (ß = 6.08, p < 0.001). In addition, the interactions between race and RHR trajectories for LVM index was significant (p < 0.05). CONCLUSION: Our findings show an association between RHR trajectories from childhood to young adulthood with cardiac mass, suggesting that monitoring RHR may help identify subpopulation at high cardiovascular risk.

Effects of Race, Cardiac Mass, and Cardiac Load on Myocardial Function Trajectories from Childhood to Young Adulthood: The Augusta Heart Study.

Background The overall goal of this longitudinal study was to determine if the Black population has decreased myocardial function, which has the potential to lead to the early development of congestive heart failure, compared with the White population. Methods and Results A total of 673 subjects were evaluated over a period of 30 years including similar percentages of Black and White participants. Left ventricular systolic function was probed using the midwall fractional shortening (MFS). A longitudinal analysis of the MFS using a mixed effect growth curve model was performed. Black participants had greater body mass index, higher blood pressure readings, and greater left ventricular mass compared with White participants (all P<0.01). Black participants had a 0.54% decrease of MFS compared with White participants. As age increased by 1 year, MFS increased by 0.05%. As left ventricular mass increased by 1 g, MFS decreased by 0.01%. As circumferential end systolic stress increased by 1 unit, MFS decreased by 0.04%. The MFS trajectories for race differed from early age to young adulthood. Conclusions Changes in myocardial function mirror the race-dependent variations in blood pressure, afterload, and cardiac mass, suggesting that myocardial function depression occurs early in childhood in populations at high cardiovascular risk such as Black participants.

Ethnic and sex differences in the longitudinal association between heart rate variability and blood pressure.

PURPOSE: Elevated blood pressure is a risk factor for increased cardiovascular morbidity and mortality. Decreased vagally-mediated heart rate variability has previously been prospectively linked with increased blood pressure; however, to date, no such prospective data exist regarding this relationship among Blacks. MATERIALS AND METHODS: We examined this association in 387 normotensive young adults (mean age, 23 years, 52% female, 54% Black) who participated in two laboratory evaluations spanning approximately six years. Blood pressure was measured at both timepoints with a non-invasive oscillometric device and heart rate variability was assessed via bio-impedance. RESULTS: In the total sample, heart rate variability significantly predicted systolic (p = .022) and diastolic (p < .001) blood pressure increases six years into the future. However, this pattern varied as a function of ethnicity and sex with the effect of heart rate variability on Time 2 systolic blood pressure only significant among White males (p = .007). Heart rate variability was also predictive of Time 2 diastolic blood pressure in White males (p = .038) as well as among both White (p = .032) and Black (p = .015) females, but was not related to blood pressure among Black males. CONCLUSION: We report for the first time significant ethnic and sex differences in the prospective relationship between heart rate variability and blood pressure change. These findings may give clues as to the underlying mechanisms that are involved in the well-known health disparities in blood pressure and hypertension-related cardiovascular diseases.

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.

Adenosine Kinase Inhibition Augments Conducted Vasodilation and Prevents Left Ventricle Diastolic Dysfunction in Heart Failure With Preserved Ejection Fraction.

BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) is often manifested as impaired cardiovascular reserve. We sought to determine if conducted vasodilation, which coordinates microvascular resistance longitudinally to match tissue metabolic demand, becomes compromised in HFpEF. We hypothesized that the metabolic vasodilator adenosine facilitates and that inhibition of ADK (adenosine kinase) augments conducted vasodilation for a more efficient myocardial perfusion and improved left ventricle (LV) diastolic function in HFpEF. METHODS AND RESULTS: We assessed conducted vasodilation in obese ZSF1 rats that develop LV diastolic dysfunction and is used to model human HFpEF. Additionally, conducted vasodilation was measured in arterioles isolated from the right atrial appendages of patients with HFpEF. We found a markedly reduced conducted vasodilation both in obese ZSF1 rats and in patients with HFpEF. Impaired conducted vasodilation was accompanied by increased vascular ADK expression. Isolated rat and human arterioles incubated with adenosine (10 nmol/L) or ADK inhibitor ABT-702 (0.1 µmol/L) both displayed augmented conducted vasodilation. Treatment of obese ZSF1 rats with ABT-702 (1.5 mg/kg, IP for 8 weeks) prevented LV diastolic dysfunction, and in a crossover design augmented conducted vasodilation and improved LV diastolic function. ABT-702 treated obese ZSF1 rats exhibited reduced expression of myocardial carbonic anhydrase 9 and collagen, surrogate markers of myocardial hypoxia. CONCLUSIONS: Upregulation of vascular ADK mitigates adenosine-facilitated conducted vasodilation in obese ZSF1 rats and in patients with HFpEF. We propose that pharmacological inhibition of ADK could be beneficial for therapeutic augmentation of conducted vasodilation, thereby improving tissue perfusion and LV diastolic function in HFpEF.

Comparison of Coronary Atherosclerotic Plaque Burden and Composition of Culprit Lesions Between Cigarette Smokers and Non-Smokers by In Vivo Virtual Histology Intravascular Ultrasound.

Cigarette smoking is a major risk factor in the progression of atherosclerosis and has been shown to cause endothelial dysfunction, inflammation, and modification of lipid profile. However, its role in the pathogenesis of vulnerable coronary plaque remains unknown. We investigated the relationship between cigarette smoking and the development of vulnerable coronary artery plaque using virtual histology intravascular ultrasound (VH-IVUS). Data from consecutive patients who underwent VH-IVUS assessment of native coronary artery stenosis during clinically indicated cardiac catheterization at our institution over a 2-year period were analyzed. Baseline demographic and study characteristics were collected on all patients. Coronary plaque compositions of the culprit lesion were compared on bivariate and multivariate analysis. We analyzed data on 160 patients with a mean age of 60 ± 11 years. Sixty-nine percent of these patients were admitted for acute coronary syndrome, 31% were smokers, and the mean plaque burden was 66%. On average, 58% of these plaques were fibrous, 19% were fibro-fatty, 18.3% had a necrotic core, and 5.4% were composed of dense calcium. Cigarette smokers had a higher burden of necrotic core (20.7% vs 17.2%; P=.04). On multivariate analysis, cigarette smoking was independently associated with a 4.54% increase in the burden of necrotic core (P=.01). Older age (>80 years) was also a predictor of higher necrotic core burden (P=.02). In conclusion, cigarette smoking is associated with a higher burden of necrotic core in coronary atherosclerotic plaques. This may represent one of the mechanisms for increased cardiovascular events.

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.

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.

Stress reduces diastolic function in youth.

OBJECTIVE: Research regarding the influence of mental stress (MS) on heart function focused primarily on heart contractility. We hypothesized that MS results in attenuated diastolic function (DF) as early as in adolescence and this effect may differ by race and sex. METHODS: 161 normotensive adolescents (81 blacks and 80 females) performed resting (control) and MS (experimental) conditions on separate visits. Visits lasted for 3 hours (1-hour rest, video game challenge and recovery for experimental visit. Mitral inflow early (E) to late (A) filling velocities (E/A) ratio; mitral valve annular early velocity (E') and E/E' ratio were recorded every 30 minutes to evaluate DF. RESULTS: BP and HR increased during experimental visit (all p values < .01). E/A ratio progressively increased during control visit (mean [SE], from 1.93 ± 0.42 to 2.01 ± 0.47) but decreased during the stress phase of experimental visit (from 1.91 ± 0.44 to 1.87 ± 0.50, p interaction < .001). In white males, E' increased from rest to stress phase (from 10.3 ± 2.55 to 10.7 ± 2.28 cm/s), whereas E' decreased in white females (from 11.0 ± 2.62 to 10.6 ± 2.53 cm/s), black males (from 10.5 ± 2.31 to 9.9 ± 2.19 cm/s), and black females (from 10.6 ± 2.22 to 10.3 ± 1.86 cm/s, p interaction < .04). During stress, higher A was associated with higher E/E' ratio. CONCLUSIONS: Recurrent episodes of mental stress may increase the risk of poor DF, and these adverse effects may be stronger in females and black males.

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.

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.

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.

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.

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.