Effect of cardiac resynchronization therapy in patients with moderate left ventricular systolic dysfunction and wide QRS complex: a prospective study.

BACKGROUND: We sought to investigate the effect of cardiac resynchronization therapy (CRT) on disease progression in patients with moderate left ventricular (LV) systolic dysfunction. METHODS AND RESULTS: This is a prospective study to explore the effect of CRT in 15 optimally treated patients (age: 66.1 +/- 12.8 years; male = 13) with New York Heart Association (NYHA) class III, LV ejection fraction >35% and <45% and QRS duration >120 msec. Echocardiographic examination and standard heart failure assessment was performed before and 3 months after CRT implantation. The magnitude of echocardiographic remodeling measurements was compared with 30 age, sex, NYHA class, and heart failure etiology matched patients with conventional CRT indication. There were significant reductions in LV end-systolic (86.2 +/- 24.1 to 69.7 +/- 22.2 mL, P < 0.01)/end-diastolic (135.5 +/- 36.8 to 120.5 +/- 34.6 mL, P < 0.01) volumes, improvement in LV ejection fraction (39.1 +/- 2.2 to 44.2 +/- 5.5%, P = 0.01), and NYHA class (3.0 +/- 0.0 to 2.07 +/- 0.46, P < 0.001). There was no difference in changes in LV volumes, ejection fraction, NYHA class, and exercise capacity before and after CRT between the study and conventional groups except for greater improvement in the quality of life score in the conventional group. CONCLUSION: In this prospective study, significant LV reverse remodeling by CRT in those with a wide QRS complex and moderate LV systolic dysfunction was observed. Further studies to explore the benefit of CRT in patients with less severe heart failure are recommended.

Rosiglitazone versus bedtime insulin in the treatment of patients with conventional oral antidiabetic drug failure: a 1-year randomized clinical trial.

This study was conducted to evaluate the efficacy and tolerability of rosiglitazone in the treatment of patients with secondary oral antidiabetic drug (OAD) failure and to directly compare its use with bedtime insulin. A total of 112 Chinese patients with type 2 diabetes and conventional OAD failure were recruited. Patients were randomly assigned to treatment with rosiglitazone or bedtime isophane insulin; they continued to take their original oral antidiabetic drugs. Glycemic index, other clinical profiles, and tolerability were assessed during treatment and 1 y after add-on treatment was provided. Among the 112 patients, mean age (+/-SD) was 58.2+/-11.0 y (median, 58 y; range, 37 to 84 y). Both rosiglitazone (n=56) and insulin (n=56) significantly improved fasting glucose (2.4 and 3.7 mmol/L, respectively) and hemoglobin A1c concentrations (1.1% and 1.3%, respectively). Both therapies increased body mass index after 1 y of treatment (0.9 and 0.8 kg/m2, respectively). Only rosiglitazone increased high-density lipoprotein cholesterol concentrations (0.1 mmol/L). Four patients (7.1%) who were given rosiglitazone developed adverse effects (2, ankle edema, and 2, gastrointestinal disturbance). Six insulin-treated patients (10.7%) described adverse effects (5, early morning hypoglycemia, and 1, anxiety). Investigators concluded that in Chinese patients with type 2 diabetes and secondary conventional OAD failure, 1 y of treatment with rosiglitazone or bedtime insulin added to the regular regimen resulted in similar improvements in glycemic control. Rosiglitazone was also associated with improved high-density lipoprotein cholesterol levels. The addition of rosiglitazone may offer a safe and effective alternative to bedtime insulin treatment.

Stabilization and regression of albuminuria in Chinese patients with type 2 diabetes: a one-year randomized study of valsartan versus enalapril.

This study was designed to compare the short-term (1-y) tolerability and antiproteinuric efficacy of enalapril and valsartan in patients with type 2 diabetes. Forty-two patients with normal renal function or early-stage nephropathy were recruited in Hong Kong and randomized to valsartan 80 mg/day or enalapril 5 mg/day; the doses were increased to 160 mg and 10 mg daily, respectively, as tolerated. Early-morning urine was analyzed for albumin and creatinine and 24-hour urinary albumin excretion at baseline and 1 year after therapy began. Twenty-two patients were randomized to valsartan and 20 to enalapril. The 2 treatment groups were similar in terms of age, sex distribution, and duration of diabetes or hypertension. Blood pressure decreased to a similar extent (-2.5% to -5.0%) with each drug. Similarly, the 24-hour urinary albumin excretion decreased by 5% to 6% with each drug. The albumin-creatinine ratio in early-morning urine samples and plasma creatinine levels decreased in the valsartan group and increased in the enalapril group, but the difference was not significant. Plasma potassium levels were stable in both groups at the end of study. Cough was reported by 7 (35%) patients receiving enalapril and none of those receiving valsartan (P=.003). In conclusion, enalapril and valsartan both reduced blood pressure and albuminuria to a similar extent with 1 year of therapy in Chinese patients with type 2 diabetes and normal renal function or early-stage nephropathy. Fewer adverse events were reported with valsartan, but both drugs appear to be relatively safe.

Restoration of nocturnal dip in blood pressure is associated with improvement in left ventricular ejection fraction. A 1-year clinical study comparing the effects of amlodipine and nifedipine retard on ambulatory blood pressure and left ventricular systolic function in Chinese hypertensive type 2 diabetic patients.

We assessed the effects of amlodipine and nifedipine retard on 24-h blood pressure (BP) control, nocturnal fall in BP and their significance on left ventricular systolic functions in 54 Chinese hypertensive type 2 diabetic patients. Patients being recruited were openly randomised to amlodipine or nifedipine retard. Ambulatory 24-h BP and echocardiogram (in 42 patients) were measured before and 1 year after treatment. At the end of study, there was 17% reduction in systolic BP; 17% reduction in diastolic BP and 12% reduction in mean arterial pressure (MAP) (no difference between amlodipine and nifedipine). Of the 42 subjects underwent echocardiograms, eight became 'new-dippers' at the end of study (non-dippers before treatment and restored nocturnal fall of MAP> or =10% after treatment). The other 34 patients were either non-dippers before and after treatment (n=27); dippers before and after treatment (n=3) or dippers before treatment and non-dippers after treatment (n=4). The eight 'new-dippers' had improved ejection fraction (69.6+/-7.2 to 75.8+/-7.4%, P<0.05) and increased left ventricular diastolic diameter (43.7+/-7.9 to 47.9+/-8.8 mm, P<0.05) after the 1-year treatment of calcium antagonist. Compared to the other 34 subjects, the eight 'new-dippers' showed significant improvement in ejection fraction (9.4+/-10.9 vs. -1.2+/-11.8%, P<0.05). In conclusion, both amlodipine and nifedipine retard are effective in controlling the 24-h BP in Chinese hypertensive type 2 diabetic patients. For those who have restored nocturnal dip in BP have significantly increased left ventricular systolic ejection fraction after 1-year treatment of long acting calcium antagonists. The clinical significance and underlying mechanisms require further studies.

Improvement of left atrial function is associated with lower incidence of atrial fibrillation and mortality after cardiac resynchronization therapy.

BACKGROUND: Left atrial (LA) volume is a predictor of cardiovascular events in patients with heart failure. Improvement of LA function and reverse remodeling was observed after cardiac resynchronization therapy (CRT). OBJECTIVE: The purpose of this study was to explore the clinical significance of improvement in LA function after CRT. METHODS: Echocardiographic studies were performed before and 3 months after CRT in 97 patients (72 men and 25 women; age 63.8 +/- 13.3 years) with standard CRT indication but no history of atrial fibrillation (AF). LA active emptying fraction based on the change in volumes (LAV-EF) were calculated, and significant improvement in LA function (LA responder) was defined as a relative increase >/=50% from baseline LAV-EF. The primary end-points were newly developed AF detected by ECG or device and all-cause mortality. RESULTS: After 1,200 +/- 705 days of follow-up, LA responders (n = 47 [48.5%]) had a significantly lower incidence of AF (12.8% vs 40%, P = .002) and mortality (17% vs 44%, P = .004) than did LA nonresponders. In Cox proportional hazard analysis, LA responders was the only independent predictor of lower risk of new-onset AF (hazard ratio 0.22, 95% confidence interval 0.08-0.61, P = .003), whereas both LA responders (hazard ratio 0.22, 95% confidence interval 0.09-0.53, P <.001) and left ventricular reverse remodeling (>10% reduction in left ventricular end-systolic volume at 3 months; hazard ratio 0.96, 95% confidence interval 0.93-0.99, P = .03) were independent predictors of lower risk of death after CRT. CONCLUSION: Improvement of LA function after CRT was associated with a lower incidence of AF and mortality in AF naïve patients with severe heart failure.

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.

Prognostic value of renal function in patients with cardiac resynchronization therapy.

BACKGROUND: Renal insufficiency is prevalent in patients with heart failure and indicates poor prognosis. We examine (i) the relationship between left ventricular (LV) reverse remodeling (RR) and renal function and (ii) the prognostic value of renal function in patients receiving cardiac resynchronization therapy (CRT). METHODS: The relationship between LV-RR, defined as a 10% reduction in LV end-systolic volume, and renal function was examined in 85 consecutive patients receiving CRT. Echocardiographic assessment and renal function tests were performed before and 3 months after CRT. All-cause mortality and the composite of mortality or heart failure hospitalization between those with preserved or deteriorated renal function at 3 months were assessed by Kaplan Meier analysis. RESULTS: There was a slight improvement in glomerular filtration rate (GFR) in those with LV-RR (n=44; 51.7+/-20.4 vs. 54.2+/-19.1 ml/min/1.73 m2; p=0.024) while a significant deterioration (n=41; 61.9+/-17 vs. 48.8+/-13.0 ml/min/1.73 m2; p<0.001) was observed in those without LV-RR. The change (Delta) in GFR was significantly correlated with DeltaLV end-systolic/diastolic volumes and DeltaLV ejection fraction. After follow up of 856.4+/-576.8 days, patients with preserved renal function had significant lower all-cause mortality (log rank chi2=4.82, p=0.029) and the composite endpoints (log rank chi2=5.04, p=0.025). CONCLUSION: Preservation of renal function was observed in patients with systolic heart failure and renal insufficiency responding to CRT and provided prognostic information. A rapid decline in renal function after CRT was associated with worse clinical outcomes.

Effect of left ventricular endocardial activation pattern on echocardiographic and clinical response to cardiac resynchronization therapy.

OBJECTIVE: To explore the left ventricular (LV) electrical activation pattern in heart failure (HF) and its implication to cardiac resynchronization therapy (CRT). DESIGN AND SETTING: Observational study at the University Teaching Hospital. PATIENTS: 23 optimally treated patients with HF with New York Heart Association class III, QRS duration >120 ms and LV ejection fraction <35%. INTERVENTIONS: The LV endocardial activation pattern and total activation time (Tat) was determined by non-contact mapping and the LV mechanical dys-synchrony was determined by standard deviation (Ts-SD) and maximal difference (Ts-diff) of time to peak systolic contraction (Ts) among 12 LV segments using tissue Doppler imaging before receiving CRT. MAIN OUTCOME MEASURES: Correlation between electrical and mechanical dys-synchrony; volumetric responder to CRT at 3 months; HF hospitalisation or death by Kaplan-Meier analysis. RESULTS: Homogenous (type I, n = 8) and presence of conduction block (type II, n = 15) patterns were identified. Significant correlation between Tat and Ts-SD/Ts-diff was noted only in type II (r = 0.73/0.56, p = 0.002/0.03). Ts-SD and Ts-diff in type II were significantly longer than type I. 12 patients in type II and 2 in type I were CRT responders (p = 0.01). After 487 (447) days, patients with type II pattern had significantly lower risk of HF hospitalisation or death than those with type I (log rank chi(2) = 5.25; p = 0.02). CONCLUSION: Patients with type II LV endocardial activation pattern had a more favourable echocardiographic and clinical response to CRT than those with type I pattern.

A 10-week Tai-Chi program improved the blood pressure, lipid profile and SF-36 scores in Hong Kong Chinese women.

BACKGROUND: Physical activity is associated with a better longevity and reduced morbidity. In addition, exercise has a mood-elevating effect, which improves self-esteem. Tai-Chi is a traditional Chinese aerobic exercise. We aimed to assess the short-term effects of Tai-Chi on the clinical parameters and health-related quality of life (QOL) in Hong Kong Chinese. MATERIAL/METHODS: Twenty Chinese healthy female subjects were recruited. There were 2 Tai-Chi sessions per week for 10 weeks. Each session lasted for one hour. Health-related QOL was assessed with SF-36 questionnaire. RESULTS: Of the 20 subjects, their mean age was 40.8 +/- 5.9 years (median 42.5 years, range 30-50 years). At the end of the study, systolic blood pressure, total cholesterol and low-density lipoprotein cholesterol levels significantly reduced (114 +/- 9 to 108 +/- 9 mmHg, p = 0.012; 4.7 +/- 0.8 to 4.4 +/- 0.5 mmol/L, p = 0.020 and 2.7 +/- 0.6 to 2.2 +/- 0.5 mmol/L, p = 0.001, respectively). Among all SF-36 items, Vitality and Mental Health significantly improved after the 10-week Tai-Chi program (64.9 +/- 8.1 to 68.4 +/- 6.6, p = 0.038 and 64.4 +/- 6.9 to 69.1 +/- 1.4, p = 0.003, respectively). CONCLUSIONS: A 10-week Tai-Chi exercise program improved systolic blood pressure, lipid profiles and some of the parameters of health-related QOL in Hong Kong Chinese women. Tai-Chi is likely to be a useful choice of physical activity. We need a larger study that covers a wider range of populations to confirm our results.

Prolongation of atrial effective refractory period with biatrial nonexcitatory stimulation.

BACKGROUND: A nonexcitatory, nonpropagating atrial extrastimulus delivered in the refractory period of the preceding cycle can prolong the atrial effective refractory period (AERP) and prevent the induction of atrial fibrillation by another AE introduced in the vulnerable period. Whether the effect of this nonexcitatory stimulation (NE) is confined only to its application site is unknown. METHODS AND RESULTS: Sixteen consecutive patients were recruited into the study and 2 patients were excluded because of development of more sustained atrial fibrillation. NE was commenced by introduction of a 2.0 msec, 20-mA impulse at 50 msec after the preceding captured pacing impulse. AERP of right atrial septum, a distant site to NE application, was determined at baseline and after 5 minutes of steady pacing at six different protocols: protocol 1, 2, and 3 were conventional pacing at high right atrium, distal coronary sinus, and biatrial sites, respectively, and protocol 4, 5, and 6 were conventional pacing together with NE applied to the same sites as protocol 1, 2, and 3. Biatrial NE (protocol 6 with median AERP = 212.5 msec) significantly prolonged AERP compared with baseline (median AERP = 202.5 msec and P < 0.05), conventional pacing (protocol 1, 2, and 3 with median AERP = 205.0 msec, 205.0 msec, and 205.0 msec, respectively, and all P < 0.05), and single-site NE (protocol 4 and 5 with median AERP = 207.5 msec and 207.5 msec, respectively, and both P < 0.05). CONCLUSION: Biatrial NE resulted in AERP prolongation even at sites distant to NE application. The study result suggests that by adding NE to multi-sites pacing for atrial fibrillation prevention may have additional benefit.

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.