Improvement in Vascular Endothelial Function following Transcatheter Aortic Valve Implantation.

Background and objectives: Endothelial dysfunction is associated with exercise intolerance and adverse cardiovascular events. Transcatheter aortic valve implantation (TAVI) is applied to treat elderly patients with severe aortic stenosis, but less is known about the impact of TAVI on endothelial dysfunction, which can be assessed by measuring flow-mediated vasodilation (FMD). In this parameter, a low value indicates impaired endothelial function. Materials and Methods: Vascular endothelial function was evaluated by FMD of the brachial artery just before and one week after TAVI. Factors associated with the normalization of FMD and their prognostic impact were investigated. Results: Fifty-one patients who underwent TAVI procedure (median 86 years old, 12 men) were included. FMD improved significantly from baseline to one week following TAVI (from 5.3% [3.7%, 6.7%] to 6.3% [4.7%, 8.1%], p < 0.001). Among 33 patients with baseline low FMD (≤6.0%), FMD normalized up to >6.0% following TAVI in 15 patients. Baseline higher cardiac index was independently associated with normalization of FMD following TAVI (odds ratio 11.8, 95% confidence interval 1.12-124; p < 0.04). Conclusions: Endothelial dysfunction improved following TAVI in many patients with severe aortic stenosis. The implication of this finding is the next concern.

High Cardiac Troponin I Is Associated With Transesophageal Echocardiographic Risk of Thromboembolism and Ischemic Stroke Events in Non-Valvular Atrial Fibrillation Patients.

BACKGROUND: Abnormalities in the left atrium (LA) detected on transesophageal echocardiography (TEE) are reliable predictors of thromboembolism in patients with atrial fibrillation (AF). Cardiac troponin I, a marker of subclinical myocardial damage, may also be a predictor of thromboembolic events in patients with AF. The relationship between cardiac troponin I and thromboembolic risk on TEE, however, remains unclear.Methods and Results:TEE and laboratory data, including high sensitivity cardiac troponin I (hs-cTnI) and CHA2DS2-VASc score, were analyzed in 199 patients with non-valvular AF (NVAF). Patients were stratified into those with or without LA abnormality, defined as LA appendage flow velocity <20 cm/s or dense spontaneous echo contrast. On multiple logistic analysis of the clinical variables, hs-cTnI was associated with LA abnormality (95% CI: 1.0003-1.020, P=0.034). The area under the curve for LA abnormality increased on addition of hs-cTnI to CHA2DS2-VASc score. The incidence rate of ischemic stroke was higher in the high hs-cTnI group than in the low-hs-cTnI group (log-rank test, P<0.05). CONCLUSIONS: Elevated hs-cTnI was independently associated with LA abnormality in NVAF patients. hs-cTnI level may be a useful biomarker for risk stratification of thromboembolism in NVAF patients.

Transesophageal echocardiographic thromboembolic risk is associated with smoking status in patients with atrial fibrillation.

BACKGROUND: Smoking is a risk factor for cardiovascular diseases, but it is unclear whether smoking status, including environmental tobacco smoke, increases stroke risk in patients with atrial fibrillation (AF). Abnormalities of the left atrium (LA) and aortic atherosclerosis, as detected by transesophageal echocardiography (TEE), are risk factors for stroke and thromboembolism in AF patients. We investigated the impact of smoking status on thromboembolic risk by TEE in patients with nonvalvular AF. METHODS: In 122 patients with AF (mean age, 63 years; chronic AF 50%) who underwent TEE before catheter ablation of AF or for detection of the potential cardioembolic source, urinary concentrations of cotinine and clinical variables including smoking status and the CHA2DS2-VASc score were determined. RESULTS: Severe aortic atherosclerosis and increased aortic wall thickness were more frequently detected by TEE in current smokers than in non-smokers (p<0.05), though these findings did not significantly differ between non-smokers and environmental smokers. Patients in AF rhythm during TEE, who were environmental smokers and at relatively low risk, as stratified by their CHA2DS2-VASc score (≤ 2), showed lower LA appendage flow velocity than those without environmental smoking (47±22 vs. 34±13 cm/sec, p<0.05). CONCLUSIONS: TEE findings indicated that smoking status could be associated with thromboembolic risk in patients with AF.

Successful Withdrawal from Dobutamine by Canagliflozin in a Diabetic Patient with Stage D Heart Failure.

Patients with stage D heart failure (HF) frequently become dependent on high doses of diuretics and inotropic agents. Recently, a sodium-glucose cotransporter 2 inhibitor (SGLT2i), an oral antidiabetic agent, has been demonstrated to have favorable effects in preventing HF. However, it remains unknown whether SGLT2i is reliable for patients with decompensated HF. We experienced a case of a patient with stage D HF for whom attempting intravenous dobutamine withdrawal was difficult even after the administration of all conventional pharmacological treatment. Administration of canagliflozin produced an additive diuretic action and correction of volume overload in combination with azosemide and tolvaptan, and resulted in successful withdrawal of dobutamine. Thus, SGLT2i might be promising for the treatment of patients with congestive HF who are refractory to conventional diuretic treatment.

Restrictive Lung Function Is Related to Sympathetic Hyperactivity in Patients With Heart Failure.

BACKGROUND: Sympathoexcitation and impaired lung function are common in patients with severe heart failure (HF). However, the association between impaired lung function and sympathoexcitation remains unknown. METHODS AND RESULTS: Muscle sympathetic nerve activity (MSNA) and clinical variables were determined in 83 HF patients with left ventricular ejection fraction (LVEF) <0.45. Restrictive and obstructive changes on spirometry were defined as reduced forced vital capacity (FVC) of <80% of predicted and a ratio of forced expiratory volume in the first second to FVC of <70%, respectively. Restrictive and obstructive changes were identified in 17 and 21 patients, respectively. MSNA was higher in patients with restrictive changes than in those without restrictive changes (84 vs 66 bursts per 100 beats; P < .01), but was similar in those with and without obstructive changes. Univariate analyses showed that FVC, estimated glomerular filtration rate (eGFR), specific activity scale, B-type natriuretic peptide level, LVEF, age, and use of aldosterone receptor blockers were significant predictors of MSNA burst incidence. Multivariate analysis revealed that FVC, LVEF, and eGFR were independent factors for increased burst incidence. Changes in FVC during follow-up negatively correlated with changes in burst rate (n = 11; P < .01). CONCLUSION: Restrictive lung function was associated with increased sympathetic nerve activity independently from HF severity.

Sympathetic Nerve Activity Efferent Drive and Beta-Blocker Treatment　- Effect of Interaction in Systolic Heart Failure.

BACKGROUND: Although both ß-blocker dose (BBD) and sympathetic activity efferent drive are associated with prognosis in chronic heart failure (HF), little is known about the prognostic value of the interaction between them. METHODS AND RESULTS: Potential prognostic variables including resting muscle sympathetic nerve activity (MSNA) were investigated in 133 patients with HF (ejection fraction [EF] <0.45). BBD was normalized to therapeutically equivalent doses of carvedilol. Primary cardiovascular endpoints included cardiovascular death and HF hospitalization. Predictors for outcomes were assessed on univariate, multivariate, and Kaplan-Meier analysis. EF was followed for 9 months after MSNA measurement in 102 patients. During the 1,419±824-day follow-up period, 24 patients died (sudden death, n=10; progressive HF, n=14). On multivariate Cox proportional hazard analysis, higher MSNA (P=0.037; HR, 2.01) and lower BBD (<5.0 mg/day; P=0.041; HR, 1.94) were independent predictors of cardiovascular events. Patients were divided into higher MSNA (≥64 bursts/100 beats) and lower MSNA groups. Although lower BBD remained an independent predictor in patients with higher MSNA, BBD was not statistically significant in patients with lower MSNA on univariate analysis. Additionally, there was a lower EF change in patients with lower BBD and higher MSNA. CONCLUSIONS: Higher BBD might be necessary to avoid cardiovascular events in HF patients with central sympathetic overactivation. (Circ J 2016; 80: 2149-2154).

Transcatheter aortic valve implantation in an elderly man with severe aortic stenosis and high surgical risk.

An 85-year-old man with severe aortic stenosis (transaortic peak velocity 4.4 m/s, mean gradient 46 mmHg and valve area 0.71 cm(2)) was admitted to our hospital due to mild exertional dyspnea (NYHA class II). He had received low-dose prednisolone (5 mg/day) plus tacrolimus hydrate (1.5 mg/day) for rheumatic arthritis and interstitial pneumonia. Although aortic valve replacement was indicated, he was considered at high risk to undergo open heart surgery because of reduced pulmonary function (FEV1.0%, 77.2%) and long-term treatment with immunosuppressive drugs. After a multidisciplinary heart team conference, the decision was made to perform transfemoral transcatheter aortic valve implantation (TAVI) using a SAPIEN XT 26 mm valve. TAVI was completed in 105 minutes without any complications. After the procedure, his symptom was improved and his activity of daily life was maintained, and he was ambulatory the next day. Aortic stenosis by degenerative calcification is becoming increasingly common as the Japanese population ages. TAVI has been used to treat patients with concomitant diseases and at high risk of open heart surgery. We herein report a case with rheumatic arthritis and interstitial pneumonia that underwent successful TAVI.

Impact of persistent smoking on long-term outcomes in patients with nonvalvular atrial fibrillation.

BACKGROUND: Although smoking is a risk factor for cardiovascular diseases, little is known about the impact of smoking on long-term outcomes in patients with atrial fibrillation (AF). METHODS: In 426 consecutive patients with nonvalvular AF (mean age, 66 years; 307 men; mean follow-up, 5.8±3.2 years), clinical variables including smoking status, CHADS2, and CHA2DS2-VASc score, incidences of cardiovascular events (stroke, myocardial infarction, or admission for heart failure), bleeding, and mortality were determined. RESULTS: Incidences of intracranial bleeding (0.7% vs 0.1%/year, p<0.01), all-cause mortality (4.9% vs 2.6%/year, p<0.01), and death from stroke (0.8% vs 0.2%/year, p<0.05) were higher in patients with history of smoking than in those without it. Incidence of intracranial bleeding was significantly higher in persistent smokers than in non-persistent smokers (1.2% vs 0.2%/year, p<0.01). History of smoking predicted all-cause mortality [hazard ratio (HR), 2.7; 95% confidence interval (CI), 1.7-4.5; p<0.01] and death from stroke (HR 4.7; 95% CI 1.0-22.3; p<0.05) independent of age, antithrombotic treatment, CHADS2, and CHA2DS2-VASc score. Persistent smoking predicted intracranial bleeding (HR 4.4; 95% CI 1.1-17.6; p<0.05) independent of age and antithrombotic treatment. CONCLUSIONS: Smoking status, independent of age, antithrombotic treatment, and clinical risk factors, predicted long-term adverse outcomes including bleeding events in patients with nonvalvular AF. There might be an obvious impact of persistent smoking on intracranial bleeding.

Hyperuricemia and transesophageal echocardiographic thromboembolic risk in patients with atrial fibrillation at clinically low-intermediate risk.

BACKGROUND: There is no clear consensus on thromboprophylaxis in patients with nonvalvular atrial fibrillation (AF) at low-intermediate thromboembolic risk. Although hyperuricemia is a risk factor for cardiovascular diseases, the relationship between serum uric acid (UA) levels and thromboembolic risk has not been fully elucidated in patients with AF. METHODS AND RESULTS: Serum UA levels and the score for congestive heart failure, hypertension, age, diabetes mellitus, prior stroke/transient ischemic attack, vascular disease and sex (ie, CHA2DS2-VASc score) were determined in 470 patients with nonvalvular AF who underwent transesophageal echocardiography (TEE) to evaluate their risk of thromboembolism. Serum UA levels were similar between the low-intermediate risk (CHA2DS2-VASc score=0 or 1) and high-risk (≥2) groups, although serum D-dimer levels were lower in the low-intermediate risk than in the high-risk group. Among patients at low-intermediate risk, serum UA levels were higher in those with TEE thromboembolic risk (TEE risk: low left atrial appendage flow, spontaneous echo contrast, thrombi, or aortic atherosclerosis) than in those without TEE risk. On multivariate analysis, the serum UA level was an independent predictor of TEE risk in AF patients at low-intermediate risk (odds ratio, 1.45; 95% confidence interval 1.09-2.00; P=0.016). CONCLUSIONS: The serum UA level was associated with thromboembolic risk on TEE in patients with nonvalvular AF at low-intermediate risk stratified by clinical risk factors.

[Clinical risk stratification schemes to predict thromboembolism in patients with atrial fibrillation].

Stroke is a serious complication associated with atrial fibrillation, but the risk can vary with clinical characteristics of individual patients. CHADS2 score is the most commonly used stratification scheme because of its simplicity. However, the predictive value for ischemic stroke has been limited in patients at "low and intermediate risk". CHA2DS2-VASc score, which extends CHADS2 scheme by considering additional stroke risk factors, has been recommended to identify "truly low risk" patients who may not need any antithrombotic treatment. This new scheme could improve decision-making for thromboprophylaxis in patients with atrial fibrillation.

Effect of adaptive servoventilation on muscle sympathetic nerve activity in patients with chronic heart failure and central sleep apnea.

BACKGROUND: Adaptive servoventilation (ASV) improves cardiac function and sympathetic nerve activity in patients with heart failure (HF). However, the mechanisms underlying these improvements remain obscure. METHODS AND RESULTS: We compared muscle sympathetic nerve activity (MSNA) and cardiorespiratory polygraphy and echocardiography findings at baseline and at 3.5 ± 0.8 months' follow-up in 32 patients with HF (New York Heart Association functional class II or III; ejection fraction <45%) and central sleep apnea (CSA; apnea-hypopnea index [AHI] ≥15/h) who consented (n = 20; ASV group) or declined (n = 12; non-ASV group) to undergo ASV treatment. Compliance with ASV and changes in AHI were determined from data collected by integral counters in devices and from cardiorespiratory polygraphic findings, respectively. Ejection fraction and MSNA significantly changed in the ASV (both P < .001) but not the non-ASV group. Although changes in AHI and MSNA correlated, the average use of ASV did not. In contrast, changes in AHI and the average use of ASV were independent predictors of changes in ejection fraction (both P < .01). CONCLUSIONS: ASV decreases MSNA and improves cardiac function in association with suppression of CSA in patients with HF.

Clinical and transesophageal echocardiographic variables for prediction of thromboembolic events in patients with nonvalvular atrial fibrillation at low-intermediate risk.

BACKGROUND: There is no clear consensus about antithrombotic treatment in atrial fibrillation (AF) patients at low-intermediate thromboembolic risk. Transesophageal echocardiography (TEE) is useful for prediction of thromboembolic events in AF. METHODS AND RESULTS: Of 498 patients with nonvalvular AF, incidence of stroke, cardiac events, and mortality was investigated in 280 patients with CHADS(2) score 0 or 1 (mean age 64 years, mean follow-up 6.4 ± 3.1 years). Left atrial abnormality (low left atrial appendage flow, spontaneous echo contrast, or thrombi), complex aortic plaque (mobile, ulcerated, pedunculate, or thickness ≥ 4mm), or both were defined as TEE risk. The incidences of ischemic stroke, cardiovascular events, and death were higher in patients with TEE risk than in those without the risk (2.0%/year vs. 0.5%/year, p<0.05; 4.7%/year vs. 1.9%/year, p<0.01; and 4.7%/year vs. 2.0%/year, p<0.01, respectively). This was also true for patients with CHADS(2) score of 0 (1.7%/year vs. 0.3%/year, p<0.05; 4.1%/year vs. 1.6%/year, p<0.05; and 3.9%/year vs. 1.4%/year, p<0.01; respectively). On multivariate analysis, TEE risk predicted ischemic stroke, cardiovascular events, and mortality independently of clinical variables or CHADS(2) score. CONCLUSIONS: TEE could be useful for further stratification of patients with nonvalvular AF stratified at low-intermediate risk (CHADS(2) score 0 or 1) and could indicate who should receive anticoagulation treatment.

Transesophageal echocardiographic findings are independent and relevant predictors of ischemic stroke in patients with nonvalvular atrial fibrillation.

BACKGROUND AND PURPOSE: Not only clinical factors, including the CHADS(2) score, but also echocardiographic findings have been reported to be useful for predicting the risk of ischemic stroke in patients with nonvalvular atrial fibrillation (NVAF). However, it remains to be determined which of these factors might be more relevant for evaluation of the risk of stroke in each patient. METHODS: In 490 patients with NVAF who underwent transesophageal echocardiography (TEE), we examined the long-term incidence of ischemic stroke events (mean follow-up time, 5.7±3.3 years). For each patient, the predictive values of gender, the CHADS(2) risk factors (congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, history of cerebral ischemia), the CHADS(2) score, and the findings on echocardiography, including TEE risk markers, were assessed. RESULTS: The ischemic stroke rate was significantly correlated with the CHADS(2) score (p<0.05). According to the results of univariate analyses, age ≥75 years, history of cerebral ischemia, CHADS(2) score ≥2, and presence of TEE risk were significantly correlated with the incidence of ischemic stroke. Cox proportional hazards regression analyses identified age ≥75 years and presence of TEE risk as significant predictors of subsequent ischemic stroke events in patients with NVAF. As compared with that in persons below 75 years of age without TEE risk, the ischemic stroke rate was significantly higher in persons who were ≥75 years of age with TEE risk (4.3 vs. 0.56%/year, adjusted hazard ratio=8.94, p<0.001). CONCLUSIONS: TEE findings might be more relevant predictors of ischemic stroke than the CHADS(2) score in patients with NVAF. The stroke risk was more than 8-fold higher in patients aged ≥75 years with TEE risk.

Anticoagulation control quality affects the D-dimer levels of atrial fibrillation patients.

BACKGROUND: Anticoagulation control quality affects the incidence of thromboembolic events in atrial fibrillation (AF) patients. However, the effects of anticoagulation control quality on the prothrombotic state of AF patients are unclear. METHODS AND RESULTS: Ninety-five AF patients who had been treated with warfarin were prospectively followed-up for 449 ± 92 days. We analyzed whether time in the therapeutic range (TTR) of the international normalized ratio (INR) of prothrombin time, percentage of INR values in the range (%INR), and coefficient of variation of INR values (CV-INR) were related to D-dimer levels. The mean values of TTR, %INR, and CV-INR were 62%, 59%, and 0.19, respectively, and their median values were 67%, 63%, and 0.19, respectively. TTR was significantly correlated with %INR (R(2) = 0.917, P<0.01), but not with CV-INR (R(2) = 0.050, P = 0.26). The mean and median D-dimer levels were 0.79 and 0.60 µg/ml, respectively. Low TTR, low %INR, and high CV-INR were found to contribute to high D-dimer levels (P = 0.02, 0.03, and 0.02, respectively). CONCLUSIONS: In AF patients treated with warfarin, not only the duration outside the target INR range, but also the fluctuation in INR level may influence the prothrombotic state.

Transient hypercapnic stress causes exaggerated and prolonged elevation of cardiac and renal interstitial norepinephrine levels in conscious hypertensive rats.

The responses of sympathetic nerve activity to transient stress can be exaggerated in salt-sensitive (SS), hypertensive subjects. Cardiac and renal interstitial norepinephrine (iNE) levels during and after transient hypercapnia were investigated in conscious SS rats. Dahl SS and salt-resistant (SR) 6-wk-old rats were fed a high-salt diet, and at 12 wk iNE levels in the heart and kidney were determined using microdialysis with probes inserted in the left ventricular (LV) wall and kidney. A telemetry system determined blood pressure and heart rate (HR) in separate animals. After recovery from the operation, data were collected before, during, and after exposure to normoxic 10% CO(2) for 25 min under unanesthetized conditions. The plasma NE concentrations at baseline did not differ between the two strains. Both cardiac and renal iNE levels were much higher in SS rats than in SR rats at baseline as well as during hypercapnic stress. After stress, the markedly increased iNE levels of SS rats were prolonged in the LV as well as in the kidney. During hypercapnic stress, HR decreased in both SS and SR rats, while sudden increases in HR immediately after the withdrawal from stress were followed by its slower reduction in SS rats compared with SR rats. In conclusion, transient hypercapnic stress causes exaggerated and prolonged elevation of iNE levels in the heart as well as in kidneys of SS animals.

Chronic kidney disease and CHADS(2) score independently predict cardiovascular events and mortality in patients with nonvalvular atrial fibrillation.

Chronic kidney disease is a risk factor for cardiovascular events, but how it relates to the prognosis associated with clinical risk factors for thromboembolism in patients with nonvalvular atrial fibrillation (AF) is not well known. Estimated glomerular filtration rate (eGFR), score for congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, and stroke/transient ischemic attack (CHADS(2)), and clinical outcomes of cardiovascular events were determined in 387 patients with nonvalvular AF (mean age 66 years, 289 men, mean follow-up 5.6 ± 3.2 years). Decreased eGFR (<60 ml/min/1.73 m(2)) combined with CHADS(2) score ≥2 was associated with higher all-cause (12.9% vs 1.4% per year, hazard ratio [HR] 6.9, p <0.001) and cardiovascular (6.5% vs 0.2% per year, HR 29.7, p <0.001) mortalities compared to preserved eGFR (≥60 ml/min/1.73 m(2)) combined with CHADS(2) score <2. This was also true for rates of cardiac events (cardiac death, nonfatal myocardial infarction, or hospitalization for worsening of heart failure, 10.4% vs 1.3% per year, HR 8.9, p <0.001), ischemic stroke (3.6% vs 0.2% per year, HR 11.0, p <0.001), and cardiovascular events (cardiac events and ischemic stroke, 13.6% vs 1.5% per year, HR 8.3, p <0.001). On multivariate analysis, CHADS(2) score ≥2, decreased eGFR, and male gender independently predicted all-cause mortality. In conclusion, combined eGFR and CHADS(2) score could be an independent powerful predictor of cardiovascular events and mortality in patients with nonvalvular AF. Long-term mortality, cardiac events, and stroke risk were >8 times higher when decreased eGFR (<60 ml/min/1.73 m(2)) was present with higher CHADS(2) score (≥2).

Short term effect of adaptive servo-ventilation on muscle sympathetic nerve activity in patients with heart failure.

Chronic heart failure (HF) is characterized by sympathetic overactivation and periodic breathing. We examined whether adaptive servo-ventilation (ASV) exerts a sympathoinhibitory effect in patients with HF via normalizing respiratory pattern. Muscle sympathetic nerve activity (MSNA), heart rate, blood pressure, respiratory pattern and oxygen saturation were examined in 29 HF patients without obstructive sleep apnea (age, 61±15years; ejection fraction, 0.32±0.09; obstructive apnea index, <5/h) before (10 min), during (30 min) and after (10 min) the application of ASV. Periodic breathing was defined as a repeated oscillation of tidal volume with regularly recurring hyperpnea and hypopnea with a variation in tidal volume of greater than 25%. The severity of respiratory instability was determined using the coefficient of variation of tidal volume (CV-TV). Of 29 patients with HF, 11 had periodic breathing and 18 did not. There was a modest positive correlation between MSNA and CV-TV (n=29, p<0.05). ASV reduced respiratory rate, CV-TV and MSNA only in the group with periodic breathing (p<0.01). Change in MSNA significantly correlated with changes in respiratory rate, CV-TV and presence of periodic breathing. However, multivariate analyses revealed that respiratory rate and CV-TV were independent predictors of change in MSNA. ASV reduces MSNA by slowing respiratory rates and stabilizing respiratory patterns in patients with HF.

Circadian changes in autonomic function in conscious rats with heart failure: effects of amiodarone on sympathetic surge.

Cardiovascular events are characterized by circadian periodicity with a peak prevalence during the awakening period, which suggests a morning surge in sympathetic activity. We developed an experimental system to determine circadian changes in heart rate (HR), blood pressure (BP), locomotor activity (Loc), respiratory rate and autonomic function in conscious, unrestrained rats. The effects of amiodarone on circadian variation of these variables were determined in rats with myocardial infarction and subsequent congestive heart failure (CHF). We continuously recorded BP, HR and Loc for 24h in rats with CHF (n=16) or after a sham operation (Sham; n=7). To determine circadian changes in sympathovagal balance, digitized BP and HR data throughout 24h were analyzed based on maximum entropy. The study was repeated after 3 weeks of oral amiodarone (50mg/kg/day) or saline administration. Baseline HR, mean BP, and Loc were higher in the dark period than in the light period (all p<0.05) in both CHF and Sham rats, which is consistent with the circadian periodicity of nocturnal animals. Low-frequency components of diastolic BP variability (LFdp), an index of sympathetic tone, were significantly higher during the awakening period (16:00-20:00) than during the sleeping period (08:00-14:00), a finding analogous to the sympathetic morning surge in men. Amiodarone suppressed this transient increase in LFdp power during the awakening period. Our experimental system could detect sympathetic surge in conscious rats. Amiodarone suppressed the sympathetic surge, which could explain, at least in part, beneficial effects of amiodarone in patients with CHF.

Relation of the severity of mitral regurgitation to thromboembolic risk in patients with atrial fibrillation.

BACKGROUND: Patients with atrial fibrillation (AF) are at risk for thromboembolism. Although mitral regurgitation (MR) could be protective against left atrial (LA) blood stasis, the relationship between the severity of MR and thromboembolic risk has not been clarified in patients with AF. METHODS: 271 patients with permanent AF underwent transesophageal echocardiography (TEE). The severity of MR was assessed by Doppler echocardiography. LA blood stasis on TEE and plasma D-dimer levels were used to evaluate the thromboembolic risk. RESULTS: Patients with severe MR (n=20) had significantly higher LA appendage peak flow velocity compared to those with no MR (n=114) and those with only mild MR (n=92) (p<0.05). The grade of LA spontaneous echo contrast (SEC) was lower in patients with severe MR compared to those with no, mild or moderate MR (severe MR 0.7±0.7 grade vs moderate MR 1.7±1.0 grade, mild MR 2.2±1.3 grade, and no MR 1.9±1.3 grade, p<0.05). Multivariate analysis revealed severe MR as a negative predictor of LA blood stasis on TEE findings (odds ratio 0.27; 95% confidence interval 0.09-0.86, p<0.05). By contrast, D-dimer level was significantly higher in patients with moderate MR compared to those with any other type of severity of MR (moderate MR 1.72±1.45 µg/ml vs severe MR 0.76±0.95 µg/ml, mild MR 0.97±1.09 µg/ml, and no MR 0.82±1.15 µg/ml, p<0.05). CONCLUSIONS: There is a protective effect of MR on LA blood stasis, but this beneficial effect on thromboembolic risk appears to be limited to patients with severe MR.