Higher Dispersion Measures of Conduction and Repolarization in Type 1 Compared to Non-type 1 Brugada Syndrome Patients: An Electrocardiographic Study From a Single Center.

Background: Brugada syndrome (BrS) is a cardiac ion channelopathy that predisposes affected individuals to sudden cardiac death (SCD). Type 1 BrS is thought to take a more malignant clinical course than non-type 1 BrS. We hypothesized that the degrees of abnormal repolarization and conduction are greater in type 1 subjects and these differences can be detected by electrocardiography (ECG). Methods: Electrocardiographic data from spontaneous type 1 and non-type 1 BrS patients were analyzed. ECG parameters were measured from leads V1 to V3. Values were expressed as median [lower quartile-upper quartile] and compared using Kruskal-Wallis ANOVA. Results: Compared to non-type 1 BrS patients (n = 29), patients with spontaneous type 1 patterns (n = 22) showed similar (P > 0.05) heart rate (73 [64-77] vs. 68 [62-80] bpm), QRS duration (136 [124-161] vs. 127 [117-144] ms), uncorrected QT (418 [393-443] vs. 402 [386-424] ms) and corrected QT intervals (457 [414-474] vs. 430 [417-457] ms), JTpeak intervals (174 [144-183] vs. 174 [150-188] ms), Tpeak- Tend intervals (101 [93-120] vs. 99 [90-105] ms), Tpeak- Tend/QT ratios (0.25 [0.23-0.27] vs. 0.24 [0.22-0.27]), Tpeak- Tend/QRS (0.77 [0.62-0.87] vs. 0.77 [0.69-0.86]), Tpeak- Tend/(QRS × QT) (0.00074 [0.00034-0.00096] vs. 0.00073 [0.00048-0.00012] ms-1), index of Cardiac Electrophysiological Balance (iCEB, QT/QRS, marker of wavelength: 3.14 [2.56-3.35] vs. 3.21 [2.85-3.46]) and corrected iCEB (QTc/QRS: 3.25 [2.91-3.73] vs. 3.49 [2.99-3.78]). Higher QRS dispersion was seen in type 1 subjects (QRSd: 34 [24-66] vs. 24 [12-34] ms) but QT dispersion (QTd: 48 [39-71] vs. 43 [22-94] ms), QTc dispersion (QTcd: 52 [41-79] vs. 46 [23-104] ms), JTpeak dispersion (44 [23-62] vs. 45 [30-62] ms), Tpeak- Tend dispersion (28 [15-34] vs. 29 [22-53] ms) or Tpeak- Tend/QT dispersion (0.06 [0.03-0.08] vs. 0.08 [0.04-0.12]) did not differ between the two groups. Type 1 subjects showed higher (QRSd × Tpeak- Tend)/QRS (25 [19-44] vs. 19 [9-30] ms) but similar iCEB dispersion (0.83 [0.49-1.14] vs. 0.61 [0.34-0.92]) and iCEBc dispersion (0.93 [0.51-1.15] vs. 0.65 [0.39-0.96]). Conclusion: Higher levels of dispersion in conduction and repolarization are found in type 1 than non-type 1 BrS patients, potentially explaining the higher incidence of ventricular arrhythmias in the former group.

Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) in clinical practice.

Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is an inherited myocardial disease characterized by fibro-fatty replacement of the right ventricular myocardium, and associated with paroxysmal ventricular arrhythmias and sudden cardiac death (SCD). It is currently the second most common cause of SCD after hypertrophic cardiomyopathy in young people <35 years of age, causing up to 20% of deaths in this patient population. This condition has a male preponderance and is more commonly found in individuals of Italian and Greek descent. To date, there is no single diagnostic test for ARVC/D and the diagnosis is made based on clinical, electrocardiographic, and radiological findings according to the Revised 2010 Task Force Criteria. In this review, we will discuss the mainstay treatment which includes pharmacotherapy, implantable cardioverter-defibrillator insertion for abortion of sudden cardiac death, and in the advanced stages of the disease cardiac transplantation.

Total cosine R-to-T for predicting ventricular arrhythmic and mortality outcomes: A systematic review and meta-analysis.

BACKGROUND: The total cosine R-to-T (TCRT), a vectorcardiographic marker reflecting the spatial difference between the depolarization and repolarization wavefronts, has been used to predict ventricular tachycardia/fibrillation (VT/VF) and sudden cardiac death (SCD) in different clinical settings. However, its prognostic value has been controversial. OBJECTIVE: This systematic review and meta-analysis evaluated the significance of TRCT in predicting arrhythmic and/or mortality endpoints. METHODS: PubMed and Embase databases were searched through December 31, 2016. RESULTS: Of the 890 studies identified initially, 13 observational studies were included in our meta-analysis. A total of 11,528 patients, mean age 47 years old, 72% male, were followed for 43 ± 6 months. Data from five studies demonstrated lower TCRT values in myocardial infarction patients with adverse events (syncope, ventricular arrhythmias, or sudden cardiac death) compared to those without these events (mean difference = -0.36 ± 0.05, p < .001; I2  = 48%). By contrast, only two studies analyzed outcomes in heart failure, and pooled meta-analysis did not demonstrate significant difference in TCRT between event-positive and event-negative patients (mean difference = -0.01 ± 0.10, p > .05; I2  = 80%). CONCLUSION: TCRT is lower in MI patients at high risk of adverse events when compared to those free from such events. It can provide additional risk stratification beyond the use of clinical parameters and traditional electrocardiogram markers. Its value in other diseases such as heart failure requires further studies.

Effects of pharmacological gap junction and sodium channel blockade on S1S2 restitution properties in Langendorff-perfused mouse hearts.

Gap junctions and sodium channels are the major molecular determinants of normal and abnormal electrical conduction through the myocardium, however, their exact contributions to arrhythmogenesis are unclear. We examined conduction and recovery properties of regular (S1) and extrasystolic (S2) action potentials (APs), S1S2 restitution and ventricular arrhythmogenicity using the gap junction and sodium channel inhibitor heptanol (2 mM) in Langendorff-perfused mouse hearts (n=10). Monophasic action potential recordings obtained during S1S2 pacing showed that heptanol increased the proportion of hearts showing inducible ventricular tachycardia (0/10 vs. 5/8 hearts (Fisher's exact test, P < 0.05), prolonged activation latencies of S1 and S2 APs, thereby decreasing S2/S1 activation latency ratio (ANOVA, P < 0.05) despite prolonged ventricular effective refractory period (VERP). It did not alter S1 action potential duration at 90% repolarization (APD90) but prolonged S2 APD90 (P < 0.05), thereby increasing S2/S1 APD90 ratio (P < 0.05). It did not alter maximum conduction velocity (CV) restitution gradient or maximum CV reductions but decreased the restitution time constant (P < 0.05). It increased maximal APD90 restitution gradient (P < 0.05) without altering critical diastolic interval or maximum APD90 reductions. Pro-arrhythmic effects of 2 mM heptanol are explicable by delayed conduction and abnormal electrical restitution. We concluded that gap junctions modulated via heptanol (0.05 mM) increased arrhythmogenicity through a delay in conduction, while sodium channel inhibition by a higher concentration of heptanol (2 mM) increased arrhythmogenicity via additional mechanisms, such as abnormalities in APDs and CV restitution.

Implantation of the Micra leadless pacemaker in a patient with a low body mass index of 16.

A 71-year-old female patient has a history of complete heart block and recurrent pacemaker site infection requiring multiple pacemaker explanations. A leadless pacemaker using passive fixation was inserted into the right ventricular apex via transvenous approach without complications. This case illustrates the feasibility of implanting a leadless pacemaker system in a small-sized adult with a low body mass index of 16 (weight: 33.7 kg, height: 145 cm) which may have potential application in elderly Asian subjects.

The Tpeak - Tend interval as an electrocardiographic risk marker of arrhythmic and mortality outcomes: A systematic review and meta-analysis.

BACKGROUND: The Tpeak - Tend interval (the interval from the peak to the end of the T wave), an electrocardiographic marker reflecting transmural dispersion of repolarization, has been used to predict ventricular tachycardia/fibrillation (VT/VF) and sudden cardiac death in different clinical settings. OBJECTIVE: This systematic review and meta-analysis evaluated the significance of the Tpeak - Tend interval in predicting arrhythmic and/or mortality end points. METHODS: PubMed, Embase, Cochrane Library, and CINAHL Plus databases were searched through November 30, 2016. RESULTS: Of the 854 studies identified initially, 33 observational studies involving 155,856 patients were included in our meta-analysis. Tpeak - Tend interval prolongation (mean cutoff value 103.3 ± 17.4 ms) was a significant predictor of the arrhythmic or mortality outcomes (odds ratio [OR] 1.14; 95% confidence interval [CI] 1.11-1.17; P < .001). When different end points were analyzed, the ORs were as follows: VT/VF, 1.10 (95% CI 1.06-1.13; P < .0001); sudden cardiac death, 1.27 (95% CI 1.17-1.39; P < .0001); cardiovascular death, 1.40 (95% CI 1.19-1.64; P < .0001); and all-cause mortality, 4.56 (95% CI 0.62-33.68; P < .0001). Subgroup analysis for each disease revealed that the risk of VT/VF or death was highest for Brugada syndrome (OR 5.68; 95% CI 1.57-20.53; P < .01), followed by hypertension (OR 1.52; 95% CI 1.26-1.85; P < .0001), heart failure (OR 1.07; 95% CI 1.04-1.11; P < .0001), and ischemic heart disease (OR 1.06; 95% CI 1.02-1.10; P = 0.001). CONCLUSION: The Tpeak - Tend interval is a useful risk stratification tool in different diseases and in the general population.

Patent foramen ovale closure versus medical therapy for stroke prevention: A systematic review and meta-analysis of randomized controlled trials.

Background: Previous randomized trials on patent foramen ovale (PFO) closure versus medical therapy for stroke prevention were inconclusive. Recently, two new randomized trials and new findings from an extended follow-up of a previous trial have been published on this topic. We conducted a systematic review and meta-analysis of randomized trials comparing PFO closure with medical therapy for stroke prevention. Methods: PubMed and Cochrane Library were searched until 16 th September 2017.  The following search terms were used for PubMed: "patent foramen ovale" AND (stroke OR embolism) and "randomized" AND "Trial". For Cochrane Library, the following terms were used: "patent foramen ovale" AND "closure" AND (stroke OR embolism). Results: A total of 91 and 55 entries were retrieved from each database using our search strategy respectively, of which six studies on five trials met the inclusion criteria. This meta-analysis included 1829 patients in the PFO closure arm (mean age: 45.3 years; 54% male) and 1972 patients in the medical therapy arm (mean age: 45.1 years; 51% male). The median follow-up duration was 50 ± 30 months. When compared to medical therapy, PFO closure significantly reduced primary endpoint events with a risk ratio [RR] of 0.60 (95% CI: 0.44-0.83, P < 0.0001; I 2: 15%). It also reduced stroke (RR: 0.50, 95% CI: 0.35-0.73, P < 0.0001; I 2: 32%) despite increasing the risk of atrial fibrillation/flutter (RR: 1.90, 95% CI: 1.23-2.93, P < 0.01; I 2: 43%). However, it did not reduce transient ischemic accident events (0.75; 95% CI: 0.51-1.10, P = 0.14; I 2: 0%), all-cause bleeding (RR: 0.89; 95% CI: 0.44-1.78, P = 0.74; I 2: 51%) or gastrointestinal complications (RR: 0.92; 95% CI: 0.32-2.70, P = 0.88; I 2: 0%). Conclusions: PFO closure significantly reduces risk of stroke when compared to medical treatment and should therefore be considered for stroke prevention in PFO patients.

First clinical experience of the safety and feasibility of total subcutaneous implantable defibrillator in an Asian population.

AIMS: The safety and feasibility of a subcutaneous implantable cardioverter-defibrillator (S-ICD) has been demonstrated in the treatment of life-threatening ventricular tachyarrhythmias (VT). Nonetheless, its safety and feasibility in an Asian population with smaller body-build is unclear. METHODS AND RESULTS: Twenty-one Asian patients who underwent S-ICD from 1 April 2014 to 2 February 2015 in five institutions in Hong Kong and Singapore were retrospectively reviewed. Twenty-one patients with a mean age of 50.0 ± 14.1 years (range 29-77 years, 82.6% male) were included. Among them, 17 (81.0%) were Chinese, 3 (14.3%) were Malay, and 1 (4.8%) was Indian. Their mean body mass index was 23.0 ± 4.0 kg/m(2). An S-ICD was implanted for primary and secondary prevention in 13 (61.9%) and 8 (38.1%) patients, respectively. The indications included Brugada syndrome (n = 6, 28.6%), ischaemic cardiomyopathy (CMP, n = 6, 28.6%), dilated CMP (n = 4, 19.0%), hypertrophic CMP (n = 2, 9.5%), and idiopathic ventricular fibrillation (n = 2, 9.5%). Three patients (14.3%) had prior infected transvenous ICD. There were no acute complications but eight wound complications (persistent wound bleeding requiring intervention = 2; delayed wound healing: upper sternal wound = 3; generator site = 1; local wound infection = 2) were observed in six (28.2%) patients. After a mean follow-up of 107.2 ± 81.3 days (range of 14-254 days), one patient underwent three successful appropriate shocks for treatment of VTs. No inappropriate therapy was documented. CONCLUSION: Our initial experience shows that S-ICD is a feasible treatment for VT among an Asian population with smaller body-build. There was nonetheless a relatively high rate of wound complications.

Comparison of left ventricular reverse remodeling induced by cardiac contractility modulation and cardiac resynchronization therapy in heart failure patients with different QRS durations.

BACKGROUND: Cardiac contractility modulation (CCM) is a new device-based therapy for advanced systolic heart failure with normal QRS duration and therefore not suitable for cardiac resynchronization therapy (CRT). Left ventricular (LV) reverse remodeling was reported in patients treated with CCM or CRT, however, the extent of response was not compared. METHODS: This observational study consisted of three groups of patients with symptomatic heart failure and LV ejection fraction <35% despite optimal medical therapy. Group 1 included those received CCM with a QRS duration <120 ms (n=33), Group 2 included those received CRT with a QRS duration of 120-150 ms (n=43), and Group 3 included those received CRT with a QRS duration >150 ms (n=56). LV end-systolic volume (LVESV) was measured at baseline and 3 months later. RESULTS: Age, gender, etiology of heart failure and baseline ejection fraction were comparable. A significant LV reverse remodeling was observed in each group. The degree of LVESV reduction was similar between Group 1 and Group 2 (-11.3 ± 1 1.8 vs. -13.6 ± 18.3%, p=0.833), however, it was greater in Group 3 (-25.0 ± 18.0%, both p<0.01). By using the reduction ≥ 15%, the responder rate was not different between Group 1 (39%) and Group 2 (42%), but significantly higher in Group 3 (68%) (χ(2)=9.514, p=0.009). CONCLUSION: CCM exhibited a similar LV reverse remodeling response to CRT for patients with a mildly prolonged QRS, though the effect was less strong when compared to CRT for patients with a very wide QRS.

Diverse patterns of longitudinal and radial dyssynchrony in patients with advanced systolic heart failure.

BACKGROUND: Little is known about the impact of QRS duration and aetiology of heart failure on the pattern of left ventricular long- and short-axis dyssynchrony. OBJECTIVE: To investigate the impact of QRS duration and aetiology of heart failure on the pattern of left ventricular long- and short-axis dyssynchrony using tissue Doppler imaging (TDI) and two-dimensional (2D) speckle tracking imaging. METHODS: 448 patients with heart failure (aged 65 ± 12 years, 75% men) with ejection fraction ≤ 35% from two cardiac centres were examined for the occurrence of longitudinal dyssynchrony by TDI, and for radial dyssynchrony by 2D speckle tracking imaging. Region(s) of the latest mechanical contraction were also determined. RESULTS: Longitudinal dyssynchrony was identified in 263 (59%) patients and radial dyssynchrony in 185 (41%). 125 (28%) patients had both longitudinal and radial dyssynchrony, 138 (31%) had only longitudinal, 60 (13%) had only radial, and 124 (28%) had neither form of dyssynchrony. TDI showed that the single most delayed segment was the septal, lateral, anterior, inferior, anteroseptal and posterior wall in 12%, 27%, 12%, 19%, 7% and 13% of patients, respectively, while multisegmental delay occurred in 10% of patients. These figures were 10%, 8%, 5%, 10%, 12%, 14% and 41%, respectively, using 2D speckle tracking. When compared between patients with wide and narrow QRS complexes, both longitudinal (63% vs 53%) and radial (49% vs 36%) dyssynchrony parameters were more frequently positive in the wide QRS group defined by QRS duration ≥ 120 ms (both p < 0.05). When compared between non-ischaemic and ischaemic patients, the prevalence of longitudinal dyssynchrony was comparable (61% vs 57%, p = 0.467), while radial dyssynchrony was marginally more common in the non-ischaemic group (47% vs 37%, p = 0.049). However, the distributions of the most delayed segment between the subgroups were similar when assessed by the same echocardiographic method. CONCLUSION: In patients with advanced systolic heart failure, the patterns of longitudinal and radial dyssynchrony are heterogeneous, and mechanical dyssynchrony tends to be more prevalent in the wide QRS group and the non-ischaemic group.

Incremental prognostic value of combining left ventricular lead position and systolic dyssynchrony in predicting long-term survival after cardiac resynchronization therapy.

The efficacy of CRT (cardiac resynchronization therapy) can be affected by a number of factors; however, the prognostic significance of the LV (left ventricular) lead position has not been explored. The aim of the present study was to examine whether a PL (posterolateral) lead position has an additional value to systolic dyssynchrony in predicting a better survival after CRT. Patients (n=134) who received CRT were followed-up for 39+/-24 months. The LV lead position was determined by cine fluoroscopy, and baseline dyssynchrony was assessed by TDI (tissue Doppler imaging). The relationship between the LV lead position/dyssynchrony and mortality was compared using Kaplan-Meier curves, followed by Cox regression analysis. The all-cause and cardiovascular mortalities were 38 and 31% respectively. The presence of dyssynchrony and a PL lead position predicted a lower all-cause mortality (29 compared with 47%; log-rank chi2=5.38, P=0.02) and cardiovascular mortality (21 compared with 41%; log-rank chi2=6.75, P=0.009) than when absent. The all-cause mortality was as high as 62% when patients had neither dyssynchrony nor a PL lead position, but was reduced to 29% when both criteria were present, and was between 45 and 46% when only one criterion was present (chi2=6.79, P=0.01). The corresponding values for cardiovascular mortality were 62% when patients had neither dyssynchrony nor a PL lead position, 36-38% when patients had either dyssynchrony or a PL lead position, and 21% when patients had both criteria present (chi2=9.54, P=0.004). Combining dyssynchrony and a PL lead position independently predicted a lower all-cause morality {HR (hazard ratio), 0.496 [95% CI (confidence interval), 0.278-0.888]; P=0.018} and cardiovascular mortality [HR, 0.442 (95% CI, 0.232-0.844); P=0.013]. In conclusion, the placement of the LV lead at a PL position provides additional value to baseline dyssynchrony in predicting a lower all-cause and cardiovascular mortality during long-term follow-up after CRT.

Identification of unusual conditions after atrial septal defect repair by systematic transthoracic echocardiographic assessment.

BACKGROUND: There is a lack of echocardiographic studies to address the detection of atrial masses and abnormal venous connections in patients with secundum atrial septal defect (ASD) repair. This study sought to demonstrate that with proper technique, these unusual conditions could be diagnosed confidently by transthoracic echocardiography. METHOD: We performed a retrospective review of all repaired ASD patients of all ages with follow-up echocardiography done at Beijing Anzhen Hospital from year 1999 to 2005. Clinical and echocardiographic features of patients with aforementioned conditions were evaluated. RESULTS: Systematic echocardiographic protocol identified 11 patients with unusual conditions, in whom four patients had atrial masses (three atrial thrombi, one inflammatory pseudotumor) and seven patients had abnormal venous connections (two inadvertent diversion of inferior vena cava to left atrium, five previously unrecognized partial anomalous pulmonary venous connections). CONCLUSION: Atrial masses and abnormal venous connections could be diagnosed through a systematic echocardiographic approach in evaluating patients with ASD repair.

The role of repeating optimization of atrioventricular interval during interim and long-term follow-up after cardiac resynchronization therapy.

BACKGROUND: Cardiac resynchronization therapy (CRT) is an effective therapy for heart failure patients with electromechanical delay. Optimization of atrioventricular interval (AVI) is a cardinal component for the benefits. However, it is unknown if the AVI needs to be re-optimized during long-term follow-up. METHODS: Thirty-one patients (66+/-11 years, 20 males) with sinus rhythm who received CRT underwent serial optimization of AVI at day 1, 3-month and during long-term follow-up by pulse Doppler echocardiography (PDE). At long-term follow-up, the optimal AVI and cardiac output (CO) estimated by non-invasive impedance cardiography (ICG) were compared with those by PDE. RESULTS: The follow-up was 16+/-11 months. There was no significant difference in the mean optimal AVI when compared between any 2 time points among day 1 (99+/-30 ms), 3-month (97+/-28 ms) and long-term follow-up (94+/-28 ms). However, in individual patient, the optimal AVI remained unchanged only in 14 patients (44%), and was shortened in 12 (38%) and lengthened in 6 patients (18%). During long-term follow-up, although the mean optimal AVIs obtained by PDE or ICG (94+/-28 vs. 92+/-29 ms) were not different, a discrepancy was found in 14 patients (45%). For the same AVI, the CO measured by ICG was systematically higher than that by PDE (3.5+/-0.8 Vs. 2.7+/-0.6 L/min, p<0.001). CONCLUSION: Optimization of AVI after CRT appears necessary during follow-up as it was readjusted in 55% of patients. Although AVI optimization by ICG was feasible, further studies are needed to confirm its role in optimizing AVI after CRT.

Usefulness of tissue Doppler velocity and strain dyssynchrony for predicting left ventricular reverse remodeling response after cardiac resynchronization therapy.

The assessment of systolic dyssynchrony by echocardiography is useful in predicting a favorable response to cardiac resynchronization therapy (CRT). Tissue Doppler velocity and tissue Doppler longitudinal strain have been suggested for this purpose. This study compared parameters of systolic dyssynchrony derived from these 2 imaging modalities for their predictive values of CRT response. Two hundred fifty-six patients from 3 different centers who received CRT were followed for 6 +/- 3 months. Parameters of systolic dyssynchrony based on tissue Doppler velocity and strain imaging were assessed for the prediction of left ventricular (LV) reverse remodeling (reduction of LV end-systolic volume > or =15%). These included time to peak systolic velocity (or peak strain) of 12 LV segments to calculate the SD (Ts-SD or Tepsilon-SD), maximal difference in delay (Ts-Diff or Tepsilon-Diff), and opposite wall delay (Ts-OW or Tepsilon-OW). The septal-to-lateral delay (Ts-Sep-Lat or Tepsilon-Sep-Lat) was also measured. LV reverse remodeling, defined as improvement in end-systolic volume > or =15%, was observed in 141 patients (55%). All 4 tissue velocity parameters predicted LV reverse remodeling, and the areas under the receiver-operating characteristic curves were 0.86, 0.85, 0.84, and 0.79 for Ts-SD, Ts-Diff, Ts-OW, and Ts-Sep-Lat, respectively (all p <0.001). The cut-off values derived from receiver-operating characteristic curve analysis were 33 ms for Ts-SD, 100 ms for Ts-Diff, 90 ms for Ts-OW, and 60 ms for Ts-Sep-Lat, and their sensitivities were 93%, 92%, 81%, and 70%, with specificities of 78%, 68%, 80%, and 76%, respectively. In contrast, none of the longitudinal strain parameters predicted LV reverse remodeling. The areas under the receiver-operating characteristic curves ranged from 0.49 to 0.53 (all p = NS). The same conclusions were obtained in subgroup analyses of QRS duration (120 to 150 vs >150 ms) and ischemic or nonischemic cause of heart failure. In conclusion, parameters of tissue Doppler longitudinal velocity, but not longitudinal strain, predicted LV reverse remodeling after CRT.

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.

Are left ventricular diastolic function and diastolic asynchrony important determinants of response to cardiac resynchronization therapy?

Cardiac resynchronization therapy (CRT) has been shown to reduce symptoms and reverse left ventricular (LV) remodeling. It is not known, however, whether diastolic function will improve after CRT and diastolic asynchrony will predict LV reverse remodeling. Seventy-six patients (mean age 65 +/- 12 years, 74% men) who received CRT were studied at baseline and after 3 months. Diastolic function was assessed by transmitral Doppler and tissue Doppler imaging. LV systolic and diastolic asynchrony were assessed by the time to peak myocardial contraction (Ts) and early diastolic relaxation (Te) using the 6 basal, 6 mid-segmental model. There were 42 responders (55%) with LV reverse remodeling (defined as a reduction of LV end-systolic volume >or=15%). Parameters of systolic function were significantly improved only in the responders. For diastolic function, there were reductions of transmitral E velocity in the 2 groups, without any change in atrial velocity or the E/A ratio. Tissue Doppler imaging revealed that myocardial early diastolic velocity was unchanged in responders but was significantly worsened in nonresponders. The systolic asynchrony index (the SD of Ts of 12 LV segments) correlated significantly with LV reverse remodeling (r = -0.64, p <0.001) but not the diastolic asynchrony index (the SD of Te of 12 LV segments) (r = -0.10, p = NS). The systolic asynchrony index was the only independent predictor of reverse remodeling (beta = -0.99, 95% confidence interval -1.41 to -0.58, p <0.001). In conclusion, CRT improves systolic function and systolic asynchrony but has a neutral effect on diastolic function and diastolic asynchrony. LV reverse remodeling response is determined by the severity of prepacing systolic asynchrony but not diastolic asynchrony or the diastolic filling pattern.

Left ventricular reverse remodeling but not clinical improvement predicts long-term survival after cardiac resynchronization therapy.

BACKGROUND: In patients with severe heart failure and dilated cardiomyopathy, cardiac resynchronization therapy (CRT) improves left ventricular (LV) systolic function associated with LV reverse remodeling and favorable 1-year survival. However, it is unknown whether LV reverse remodeling translates into a better long-term prognosis and what extent of reverse remodeling is clinically relevant, which were investigated in this study. METHODS AND RESULTS: Patients (n=141) with advanced heart failure (mean+/-SD age, 64+/-11 years; 73% men) who received CRT were followed up for a mean (+/-SD) of 695+/-491 days. The extent of reduction in LV end-systolic volume (LVESV) at 3 to 6 months relative to baseline was examined for its predictive value on long-term clinical outcome. The cutoff value for LV reverse remodeling in predicting mortality was derived from the receiver operating characteristic curve. Then the relation between potential predictors of mortality and heart failure hospitalizations were compared by Kaplan-Meier survival analysis, followed by Cox regression analysis. There were 22 (15.6%) deaths, mostly due to heart failure or sudden cardiac death. The receiver operating characteristic curve found that a reduction in LVESV of > or =9.5% had a sensitivity of 70% and specificity of 70% in predicting all-cause mortality and of 87% and 69%, respectively, for cardiovascular mortality. With this cutoff value, there were 87 (61.7%) responders to reverse remodeling. In Kaplan-Meier survival analysis, responders had significantly lower all-cause morality (6.9% versus 30.6%, log-rank chi2=13.26, P=0.0003), cardiovascular mortality (2.3% versus 24.1%, log-rank chi2=17.1, P<0.0001), and heart failure events (11.5% versus 33.3%, log-rank chi2=8.71, P=0.0032) than nonresponders. In the Cox regression analysis model, the change in LVESV was the single most important predictor of all-cause (beta=1.048, 95% confidence interval=1.019 to 1.078, P=0.001) and cardiovascular (beta=1.072, 95% confidence interval=1.033 to 1.112, P<0.001) mortality. Clinical parameters were unable to predict any outcome event. CONCLUSIONS: A reduction in LVESV of 10% signifies clinically relevant reverse remodeling, which is a strong predictor of lower long-term mortality and heart failure events. This study suggests that assessing volumetric changes after an intervention in patients with heart failure provides information predictive of natural history outcomes.

Improvement of serum NT-ProBNP predicts improvement in cardiac function and favorable prognosis after cardiac resynchronization therapy for heart failure.

BACKGROUND: Cardiac resynchronization therapy (CRT) is now an established therapy for patients with advanced heart failure with electromechanical delay, although nonresponders have been observed. Because natriuretic peptides are relevant markers to reflect the severity of heart failure and filling pressure of cardiac chambers, it may be helpful to assess the efficacy of CRT. METHODS AND RESULTS: Forty-two patients with heart failure with QRS of >120 msec were recruited; their serial N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels were measured at baseline and at 1 and 3 months after CRT. There was a reduction in NT-proBNP level 1 month after CRT (2655 +/- 2242 pg/mL vs 2149 +/- 2033 pg/mL; P = .03), which was further reduced at 3 months (1473 +/- 1786 pg/mL; P < .001 vs baseline). The reduction of NT-proBNP correlated with the change of left ventricular (LV) end-systolic volume (r = 0.53; P = .001) or LV ejection fraction ( r = -0.49; P = .002) and with improvement in exercise capacity after CRT for 3 months (r = 0.50; P = .002). The patients were classified by the degree of reduction in NT-proBNP as group 1 (reduction of > or =50% vs baseline; n = 19) and group 2 (reduction of <50% vs baseline; n = 23). The degree of LV reverse remodeling (-31.8 +/- 24.7 mL vs -12.6 +/- 19.2 mL; P = .007) and gain in LV ejection fraction (+12.5% +/- 8.8% vs +4.6% +/- 5.8%; P = .002) were significantly better in group 1 than group 2. Both the all-cause mortality rate (Log-rank chi 2 = 4.01; P = .04) and the composite end-point of mortality rate or hospitalization rate for cardiovascular causes (Log-rank chi 2 = 4.31; P = .02) were significantly lower in group 1 than in group 2. CONCLUSION: Serial monitoring of NT-proBNP may be helpful to predict a favorable outcome after CRT. Those who had a reduction of NT-proBNP level of >/=50% were more likely to exhibit a favorable response.