Diastolic and systolic asynchrony in patients with diastolic heart failure: a common but ignored condition.

OBJECTIVES: The present study aimed to examine whether diastolic and systolic asynchrony exist in diastolic heart failure (DHF) and their prevalence and relationship to systolic heart failure (SHF) patients. BACKGROUND: Few data exist on mechanical asynchrony in DHF. METHODS: Tissue Doppler echocardiography was performed in 373 heart failure patients (281 with SHF and 92 with DHF) and 100 normal subjects. Diastolic and systolic asynchrony was determined by measuring the standard deviation of time to peak myocardial systolic (Ts-SD) and peak early diastolic (Te-SD) velocity using a 6-basal, 6-mid-segmental model, respectively. RESULTS: Both heart failure groups had prolonged Te-SD (DHF vs. SHF vs. controls subjects: 32.2 +/- 18.0 ms vs. 38.0 +/- 25.2 ms vs. 19.5 +/- 7.1 ms) and Ts-SD (31.8 +/- 17.0 ms vs. 36.7 +/- 15.2 ms vs. 17.6 +/- 7.9 ms) compared with the control group (all p < 0.001 vs. control subjects). Based on normal values, the DHF group had comparable diastolic (35.9% vs. 43.1%; chi-square = 1.48, p = NS), but less systolic asynchrony than the SHF group (39.1% vs. 56.9%; chi-square = 8.82, p = 0.003). Normal synchrony, isolated systolic, isolated diastolic, and combined asynchrony were observed in 39.1%, 25.0%, 21.7%, and 14.1% of DHF patients, respectively, and these were 25.6%, 31.3%, 17.4%, and 25.6%, correspondingly, in SHF (chi-square = 10.01, p = 0.019). The correlation between systolic and diastolic asynchrony, and between the myocardial velocities and corresponding mechanical asynchrony appeared weak. A wide QRS duration (>120 ms) was rare in DHF (10.9% vs. 37.7% in SHF) (chi-square = 16.69, p < 0.001). CONCLUSIONS: Diastolic and/or systolic asynchrony was common in 61% of DHF patients despite narrow QRS complex. The presence of asynchrony was not related to myocardial systolic or diastolic function. Systolic and diastolic asynchrony were not tightly coupled, implying distinct mechanisms.

Suboptimal medical therapy in patients with systolic heart failure is associated with less improvement by cardiac resynchronization therapy.

BACKGROUND: Proven medical therapy is under-prescribed in heart failure (HF) for various reasons. Cardiac resynchronization therapy (CRT) is of proven value in selected patients with HF; however, the degree of benefit in those without the optimal therapy is not clear. METHODS: This is a retrospective study comparing the effect of CRT in 30 patients without optimal combination therapy (group 1; 10 (33%) without ACEi or equivalent and 25 (83%) without beta-blockers) to an age, sex, ejection fraction (EF) and New York Heart Association (NYHA) class matched control but with the combination (group 2; n=30) at baseline. All patients were in NYHA class III or IV with EF < or = 35% and QRS interval > or = 120 ms. Echocardiographic examination and N-terminal pro-brain natriuretic peptide (NT pro-BNP) levels before and 3 months after CRT were compared between the two groups. The composite endpoints of HF hospitalization or death during follow-up were compared by Kaplan-Meier analysis. RESULTS: There were significantly less improvement in EF (+4.0+/-2.5% vs +10.1+/-3.2%; p<0.05) and degree of reverse remodeling in group 1 after 3 months. Patients in group 1 had significantly higher level of NT pro-BNP levels at 3 months (2221+/-2001 pg/mL vs 1038+/-905 pg/mL; p<0.001) and higher rates of HF hospitalization or death (53.3% vs 23.3%; Log rank chi2 5.52; p=0.019). CONCLUSION: Patients receiving CRT but without optimal medical therapy were associated with less echocardiographic and clinical improvement. Optimal medical therapy, if tolerated, before CRT is necessary.

Benefits of cardiac resynchronization therapy for heart failure patients with narrow QRS complexes and coexisting systolic asynchrony by echocardiography.

OBJECTIVES: This study was designed to evaluate the role of cardiac resynchronization therapy (CRT) in heart failure (HF) patients with narrow QRS complexes (<120 ms) and echocardiographic evidence of mechanical asynchrony. BACKGROUND: Cardiac resynchronization therapy is currently recommended to advanced HF patients with prolonged QRS duration. Echocardiographic assessment of systolic mechanical asynchrony has been proven useful to predict a favorable response after CRT. METHODS: A total of 102 HF patients with New York Heart Association (NYHA) functional class III or IV were enrolled. Among them, 51 had wide QRS (>120 ms) and 51 had narrow QRS (<120 ms). Tissue Doppler imaging (TDI) was employed to select patients with systolic asynchrony (increased asynchrony index) in the narrow-QRS group. Clinical and echocardiographic assessments were performed at baseline and 3 months after CRT. RESULTS: There was a significant reduction of left ventricular (LV) end-systolic volume in both narrow (122 +/- 42 cc vs. 103 +/- 47 cc, p < 0.001) and wide (148 +/- 74 cc vs. 112 +/- 64 cc, p < 0.001) QRS groups. Improvement of NYHA functional class (both p < 0.001), maximal exercise capacity (both p < 0.05), 6-min hall-walk distance (both p < 0.01), ejection fraction (both p < 0.001), and mitral regurgitation (both p < 0.005) was also observed. In both groups, the degree of baseline mechanical asynchrony determined LV reverse remodeling to a similar extent, as shown by the superimposed regression lines. Withholding CRT for 4 weeks resulted in loss of echocardiographic benefits. CONCLUSIONS: Cardiac resynchronization therapy for HF patients with narrow QRS complexes and coexisting mechanical asynchrony by TDI results in LV reverse remodeling and improvement of clinical status. The amplitude of benefit is similar to the wide-QRS group provided that similar extent of systolic asynchrony is selected.

Prevalence of amiodarone-related hepatotoxicity in 720 Chinese patients with or without baseline liver dysfunction.

BACKGROUND: The prevalence of hepatotoxicity after longterm oral amiodarone therapy in Chinese patients with or without elevated liver enzymes at baseline is unknown. HYPOTHESIS: Amiodarone may still be safely prescribed for Chinese patients who have baseline liver dysfunction. METHODS: This is a retrospective cross-sectional study. Significant liver dysfunction (SLD) was defined as alanine aminotransferase (ALT) > 2 times upper limit of normal range. RESULTS: Baseline liver function was checked in 628 of the 720 Chinese patients identified. The mean duration of amiodarone use was 615.9 +/- 703.1 days. Ninety patients (14.3%) had elevated baseline ALT. The prevalence of SLD was 3.7% (confidence interval [CI] 2.1-5.3%) and 4.4% (CI 0.2-8.6%) in patients with normal (n = 538) and elevated (n = 90) baseline ALT, respectively (p = 0.765). Therapy was continued in 42 patients with elevated baseline ALT until final follow-up. Eight of these (19.0%) had elevated ALT upon final follow-up, but the derangement was mild (mean ALT 134.8 +/- 145.9 IU/l, median 76 IU/l). During follow up, 24 patients developed SLD and half of these subsequently withdrew from therapy. The ALT levels at final follow-up had improved over time in both groups, but the mean difference was not significant (255.1 +/- 706.4 vs. 131.0 +/- 207.5 IU/l, p = 0.312). CONCLUSION: The prevalence of SLD in Chinese patients taking oral amiodarone with or without elevated baseline ALT was similar (4.4 vs. 3.7%). It seems that amiodarone may be safely prescribed in patients with elevated baseline ALT.

Differential change in left ventricular mass and regional wall thickness after cardiac resynchronization therapy for heart failure.

AIMS: LV reverse remodelling has been shown to be a favourable response after cardiac resynchronization therapy (CRT) in many clinical trials. This study investigated whether left ventricular (LV) reverse remodelling after CRT has any structural benefit, which include the improvement of LV mass or regional wall thickness. METHODS AND RESULTS: Fifty patients (66 +/- 11 years) receiving CRT were followed up for at least 3 months. Echocardiography with tissue Doppler imaging was performed serially before and at day 1 and 3 months after CRT. Although LV end-systolic volume (LVESV) was decreased at day 1 after CRT (141 +/- 74 vs. 129 +/- 71 cm(3), P < 0.001), further LV reverse remodelling was observed at 3 months (110 +/- 67 cm(3), P < 0.001 vs. day 1). LV ejection fraction increased at day 1 (26.5 +/- 9.3 vs. 28.5 +/- 9.1%, P < 0.005) and was further improved at 3 months (34.2 +/- 10.5%, P < 0.001 vs. day 1). However, reduction of LV mass (231 +/- 67 vs. 213 +/- 59 g, P < 0.001) and regional wall thickness was only observed at 3 months, but not at day 1. The improvement of LV mass correlated with the change in LVESV (r = 0.66, P < 0.001) and the baseline systolic asynchrony index (Ts-SD) (r = -0.52, P < 0.001). LV mass was only decreased significantly in responders of LV reverse remodelling (245 +/- 66 vs. 207 +/- 61 g, P < 0.001), but increased in non-responders (209 +/- 64 vs. 223 +/- 56 g, P = 0.02). Responders had significant decrease in thickness of all the four walls for -6 to -11% (all P < or =0.02), whereas non-responders had increased thickness in septal and lateral walls for +11% (both P < 0.05). CONCLUSION: The acute reduction in LV volume after CRT is mediated by haemodynamic and geometric benefits without actual changes in LV mass. However, at 3-month follow-up, reduction in LV mass and regional wall thickness was demonstrated, which represents structural reverse remodelling. Such benefit was only observed in volumetric responders but was worsened in non-responders.

Effect of age and heart rate on atrial mechanical function assessed by Doppler tissue imaging in healthy individuals.

BACKGROUND: The potential usefulness of Doppler tissue imaging (DTI) to assess atrial mechanical function in cardiac disease has been demonstrated. However, there are few reports on normal values of atrial function by DTI analysis. METHODS: Echocardiography with color-coded DTI was performed in 131 healthy control subjects. The peak atrial contraction velocity (V(A)) and the timing of mechanical events were assessed offline at the left atrial (LA) and right atrial (RA) free wall and interatrial septum. RESULTS: V(A) was higher in the RA (9.0 +/- 2.6 cm/s) than the LA (7.5 +/- 2.4 cm/s, P < .001), and both sites were higher than the interatrial septum (5.6 +/- 1.3 cm/s, both P < .001). The interatrial delay was 24 +/- 21 milliseconds. V(A) at the LA was higher in the participants aged 60 years or older than those who were younger than 60 years (8.1 +/- 2.7 vs 6.7 +/- 1.4 cm/s, P < .001), as was the velocity at the RA (9.6 +/- 2.8 vs 8.0 +/- 2.1 cm/s, P < .01). V(A) at the LA was higher in the participants with heart rate of 60/min or higher than those with lower heart rate (7.9 +/- 2.5 vs 6.8 +/- 1.8 cm/s, P < .05). Sex difference had no effect on V(A) and timings of atrial events. CONCLUSIONS: Assessment of atrial mechanical function by DTI is feasible in healthy individuals. The V(A) is the highest at the RA, followed by LA, and the lowest at the interatrial septum. Older age and faster heart rate seems to augment V(A) in the atrial walls.

Tissue Doppler echocardiographic evidence of atrial mechanical dysfunction in coronary artery disease.

BACKGROUND: Atrial function is an integral part of cardiac function which is often neglected. The presence of coronary artery disease (CAD) may impair atrial function. This study investigated if atrial mechanical dysfunction was present in patients with CAD by tissue Doppler echocardiography (TDI). METHODS: Echocardiography with TDI was performed in 118 patients with CAD, and compared with 100 normal controls with comparable age and heart rate. Regional atrial function was assessed at the left (LA) and right (RA) atrial free wall and inter-atrial septum (IAS). The peak regional atrial contraction velocity of (V(A)) and the timing of mechanical events were compared. RESULTS: The V(A) in the LA (5.0+/-2.6 Vs 7.7+/-2.6 cm/s), IAS (4.8+/-1.7 Vs 5.7+/-1.5 cm/s) and RA (6.8+/-3.1 Vs 9.2+/-2.9 cm/s) were significantly decreased in patients with CAD when compared with controls (all p<0.001). Patients with impaired systolic function (ejection fraction50% (both p<0.001); and were lower in those with restrictive filling pattern (RFP) than non-RFP of diastolic dysfunction (both p<0.05). The V(A) in all the subgroups was lower than controls. In contrast, transmitral atrial velocity was unable to reveal any abnormality except in the subgroup with a RFP. The LA dimension, area and volume were increased in the disease groups, but were largely unchanged in the RA despite abnormal V(A). The physiological inter-atrial delay for the onset and peak atrial contraction between the RA and LA were unaffected by CAD. CONCLUSIONS: The atrial contractile function in both atria was impaired in the presence of CAD, especially in the LA. This was detected even in patients with preserved systolic function or mild diastolic dysfunction such as non-RFP. Direct assessment of atrial velocity by TDI may better reflect atrial mechanical function than transmitral atrial velocity.

Comparison of efficacy of reverse remodeling and clinical improvement for relatively narrow and wide QRS complexes after cardiac resynchronization therapy for heart failure.

INTRODUCTION: Cardiac resynchronization therapy (CRT) has been shown to reverse left ventricular (LV) remodeling and improve symptoms in heart failure patients with wide QRS complexes; however, its role in patients with mildly prolonged QRS complexes is unclear. This study investigated if CRT benefited patients with mildly prolonged QRS complexes >120 to 150 ms and explored if the severity of systolic asynchrony determined such a response. METHODS AND RESULTS: Fifty-eight patients (age 66 +/- 11 years, 66% male) who had undergone CRT were studied prospectively. Of these patients, 27 had QRS duration between 120 and 150 ms (group A), and 31 had QRS duration >150 ms (group B). Tissue Doppler echocardiography and clinical assessment were performed at baseline and 3 months after CRT. Both groups had significant reduction of LV volume and increased ejection fraction, +dP/dt, and sphericity index (all P < 0.05). These improvements were greater in group B and were explained by the higher prevalence of systolic intraventricular asynchrony. Significant reverse remodeling (reduction of LV end-systolic volume >15%) was evident in 46% of group A patients and 68% of group B patients. Improvement in clinical endpoints was observed in both groups (all P < 0.01), although the changes in metabolic equivalent and New York Heart Association functional class were greater in group B. In both groups, systolic asynchrony index (TS-SD) was the most important predictor of reverse remodeling (r =-0.78, P < 0.001) and was the only independent predictor in the multivariate model (beta=-1.80, confidence interval =-2.18 to -1.42, P < 0.001); QRS duration was not. A predefined TS-SD value >32.6 ms had a sensitivity of 94% and specificity of 83% to predict reverse remodeling. Improvement of intraventricular asynchrony after CRT was evident only in responders (P = 0.01). CONCLUSION: Improvement of LV remodeling and clinical status is evident after CRT in heart failure patients with QRS duration >120 to 150 ms. These responders are closely predicted by the severity of prepacing intraventricular asynchrony but not QRS duration.

Tissue Doppler imaging is superior to strain rate imaging and postsystolic shortening on the prediction of reverse remodeling in both ischemic and nonischemic heart failure after cardiac resynchronization therapy.

BACKGROUND: A number of noninvasive techniques have been used to predict the effectiveness of cardiac resynchronization therapy (CRT) in heart failure patients, in particular left ventricular (LV) reverse remodeling. This study compared the relative predictive values of tissue Doppler imaging (TDI) and strain-rate imaging (SRI) parameters for LV reverse remodeling in patients who received CRT and examined for potential differences in ischemic (n=22) and nonischemic (n=32) heart failure. METHODS AND RESULTS: TDI and SRI were performed at baseline and 3-month follow-up. Eighteen parameters of intraventricular and interventricular asynchrony based on the time to peak myocardial contraction (Ts) and time to peak strain rate (Tsr) were compared, along with postsystolic shortening (PSS). Reverse remodeling with reduction of LV end-diastolic and end-systolic volumes and gain in ejection fraction (all P<0.001) was observed in the whole study population. The standard deviation of Ts of 12 LV segments (Ts-SD) is the most powerful predictor of reverse remodeling in both the ischemic (r=-0.65, P<0.001) and nonischemic (r=-0.79, P<0.001) groups. The PSS of 12 LV segments was a good predictor only for the nonischemic (r=-0.64, P<0.001) but not the ischemic (r=0.32, P=NS) group. However, parameters of SRI and interventricular asynchrony failed to predict reverse remodeling. By multiple regression analysis, independent parameters included Ts-SD in both groups (P<0.005) and PSS of 12 LV segments in the nonischemic group (P=0.03). The area of the receiver operating characteristic curve was largest for Ts-SD (0.94; CI=0.88 to 1.00). CONCLUSIONS: Ts-SD is the most powerful predictor of LV reverse remodeling and was consistently useful for ischemic and nonischemic heart failure. However, PSS is useful only for nonischemic pathogenesis, whereas the role of SRI parameters was not supported by the present study.

Effect of N-acetylcysteine for prevention of contrast nephropathy in patients with moderate to severe renal insufficiency: a randomized trial.

BACKGROUND: The effect of N-acetylcysteine (NAC) to prevent contrast nephropathy (CN) in patients with moderate to severe renal insufficiency undergoing coronary angiography or interventions is not clear. METHODS: This is a prospective, open-label, randomized, controlled trial. Ninety-one consecutive patients with a serum creatinine level of 1.69 to 4.52 mg/dL (149 to 400 micromol/L) undergoing coronary procedures were recruited and randomly assigned to administration of either oral NAC, 400 mg, thrice daily the day before and day of the contrast procedure (the NAC group) or no drug (the control group). Serum creatinine was measured before and 48 hours after contrast exposure. The primary end point of this study was the development of CN, defined as an increase in serum creatinine concentration of 0.5 mg/dL or greater (> or =44 micromol/L) or a reduction in estimated glomerular filtration rate (GFR) of 25% or greater of the baseline value 48 hours after the procedure. RESULTS: There were no significant differences between the 2 groups (46 patients, NAC group; 45 patients, control group) in baseline characteristics or mean volume of contrast agent administered. Six patients (13.3%) in the control group and 8 patients (17.4%) in the NAC group developed CN (P = 0.8). Serum creatinine levels increased from 2.27 +/- 0.54 to 2.45 +/- 0.65 mg/dL (201 +/- 48 to 217 +/- 57 micromol/L; P = 0.003) in the NAC group and 2.37 +/- 0.61 to 2.40 +/- 0.70 mg/dL (210 +/- 54 to 212 +/- 62 micromol/L; P = 0.6) in the control group. The increase in serum creatinine levels between the 2 groups had no difference (P = 0.7). Estimated GFR decreased from 30.3 +/- 8.4 to 28.1 +/- 8.4 mL/min (P = 0.01) in the NAC group and 28.4 +/- 8.6 to 27.5 +/- 8.8 mL/min (P = 0.3) in the control group. The decline in estimated GFR between the 2 groups had no difference (P = 0.7). CONCLUSION: In the current study, oral NAC had no effect on the prevention of CN in patents with moderate to severe renal insufficiency undergoing coronary angiography or interventions. However, the sample size of our present study is small. Our findings highlight the need for a large-scale, randomized, controlled trial to determine the exact beneficial effect of NAC.

Ablation of nonsustained or hemodynamically unstable ventricular arrhythmia originating from the right ventricular outflow tract guided by noncontact mapping.

Conventional activation or pacemapping is effective in guiding ablation of ventricular tachyarrhythmia originating from right ventricular outflow tract (RVOT). However, in selected patients with hemodynamically unstable or nonsustained tachycardia, noncontact mapping may be an effective alternative method to guide ablation in RVOT. Five patients with symptomatic hypotension during ventricular tachycardia (VT) or nonsustained tachyarrhythmia originating from the RVOT had radiofrequency ablation guided by noncontact mapping. All patients had a history of syncope and the tachyarrhythmias were refractory to antiarrhythmic therapy. Four patients had spontaneous sustained VT of a cycle length from 250 to 300 ms and one had symptomatic ventricular ectopic beats. Two patients were diagnosed to have arrhythmogenic right ventricular cardiomyopathy (ARVC). Sustained VT with hypotension was induced in two patients and nonsustained VT in three patients. Isopotential color maps were used to locate the earliest activation site of the tachyarrhythmia in RVOT. Three patients had tachyarrhythmia exit sites at the septal region and two at lateral region of RVOT. Low voltage area and diastolic activity were detected in the two patients with ARVC. Radiofrequency ablation guided by noncontact mapping was performed during sinus rhythm in all patients. The number of ablation attempts ranged from 1 to 14. After follow-up for 12 +/- 5.8 months, there was no recurrence of tachyarrhythmia and syncope in all five patients. Noncontact mapping is a safe and effective alternative method to guide ablation of hemodynamically unstable or nonsustained ventricular arrhythmia originating from RVOT.

Role of beta-blocker therapy in heart failure and atrial fibrillation.

Heart failure is a serious disorder associated with substantial morbidity and mortality. Approximately 15-30% patients with systolic heart failure are in atrial fibrillation and the proportion increases with severity of heart failure. Patients with heart failure and atrial fibrillation have worse outcome than those in sinus rhythm. Beta-blockers, together with angiotensin-converting enzymes inhibitors, are the standard therapy in patients with chronic heart failure. Retrospective studies have suggested that despite the improvement in left ventricular systolic function after treatment with beta-blockers, the exercise capacity and symptoms in those heart failure patients with atrial fibrillation was not improved as much as those in sinus rhythm. Moreover, the use of bisoprolol in the Cardiac Insufficiency Bisoprolol Study II, unlike those in sinus rhythm, failed to produce any survival benefit in patients with poor systolic function and atrial fibrillation. It seems that those patients with heart failure and atrial fibrillation may have different response to beta-blocker therapy. Prospective trials to clarify the impact of beta-blocker therapy and the optimal therapeutic strategy in this high-risk group of patients are warranted.

Brugada syndrome unmasked by febrile illness.

The ionic mechanisms responsible for the electrocardiographic phenotype of the Brugada syndrome are temperature dependent. This report describes a healthy young man with ECG changes typical of Brugada syndrome that were unmasked during a febrile illness.