Safety and efficacy of a novel hyperaemic agent, intracoronary nicorandil, for invasive physiological assessments in the cardiac catheterization laboratory.

AIMS: Maximal hyperaemia is a key element of invasive physiological studies and adenosine is the most commonly used agent. However, infusion of adenosine requires additional venous access and can cause chest discomfort, bronchial hyper-reactivity, and atrioventricular conduction block. The aim of this study was to evaluate the feasibility and efficacy of intracoronary (IC) nicorandil as a novel hyperaemic agent for invasive physiological studies. METHODS AND RESULTS: We enrolled 210 patients who underwent fractional flow reserve (FFR) measurement. Hyperaemic efficacy of the following methods was compared: IC bolus injection of adenosine; intravenous (i.v.) infusion of adenosine (140 µg/kg/min); and IC bolus of nicorandil (1 and 2 mg). In 70 patients, the index of microcirculatory resistance was also measured. Hyperaemic efficacy of IC nicorandil 2 mg was non-inferior to that of i.v. adenosine infusion (FFR: 0.82 ± 0.10 vs. 0.82 ± 0.10; P for non-inferiority < 0.001). There was a strong correlation between FFRs measured by i.v. adenosine and IC nicorandil (R² = 0.934). Nicorandil produced fewer changes in blood pressure, heart rate and PR interval, and less chest pain than adenosine (all P-values < 0.05). Atrioventricular block occurred in 12 patients with IC adenosine, 4 patients with i.v. adenosine and none with IC nicorandil. The index of microcirculatory resistance was 18.3 ± 8.7 with i.v. adenosine and 17.2 ± 7.6 with IC nicorandil (P = 0.126). CONCLUSION: This study suggests that IC bolus injection of nicorandil is a simple, safe, and effective way to induce steady-state hyperaemia for invasive physiological evaluations. Clinicaltrials.gov number: NCT01331902.

Comparison of 2 point-of-care platelet function tests, VerifyNow Assay and Multiple Electrode Platelet Aggregometry, for predicting early clinical outcomes in patients undergoing percutaneous coronary intervention.

BACKGROUND: Various platelet function tests are currently used to measure responsiveness to antiplatelet therapy. We sought to compare 2 point-of-care platelet function tests, VerifyNow Assay (Accumetrics, San Diego, CA) and Multiple Electrode Platelet Aggregometry (MEA) (Dynabyte, Munich, Germany), for predicting early clinical outcomes after percutaneous coronary intervention. METHODS: Platelet reactivity in the arachidonic acid-induced and adenosine diphosphate (ADP)-induced platelet aggregation was measured simultaneously with the VerifyNow Assay and MEA in 222 patients undergoing percutaneous coronary intervention between August and October 2009. We investigated the correlations between the 2 tests and performed receiver operating characteristic curve analysis for major adverse cardiovascular events (MACE), a composite of death, myocardial infarction (MI), stroke, and target vessel revascularization, at 30 days. RESULTS: Major adverse cardiovascular events occurred in 19 patients (8.6%), including 14 patients with periprocedural MI and 5 patients with stroke. Correlations were weak between the 2 tests in the arachidonic acid-induced (Spearman r = 0.189, P = .006) and ADP-induced platelet reactivity (Spearman r = 0.390, P < .001). Although the VerifyNow P2Y12 Assay (Accumetrics) was able to predict periprocedural MI (area under the aggregation curve 0.680, P = .024) and 30-day MACE (area under the aggregation curve 0.649, P = .032), VerifyNow Aspirin Assay (Accumetrics), MEA ASPI test, and MEA ADP test failed to predict such clinical events. Hyporesponsiveness to clopidogrel based on the VerifyNow Assay was associated with about a 6-fold increased risk of MACE at 30 days. CONCLUSIONS: Hyporesponsiveness to clopidogrel measured by VerifyNow Assay was able to identify patients with dual antiplatelet therapy who were at higher risk for periprocedural MI and MACE at 30 days. Further randomized studies are required to validate the effectiveness of different platelet function tests for predicting long-term clinical outcomes.

Comparison of plain balloon and cutting balloon angioplasty for the treatment of restenosis with drug-eluting stents vs bare metal stents.

BACKGROUND: The efficacy of cutting or plain balloon angioplasty (CBA or PBA) has not been analyzed for the treatment of drug-eluting stent (DES) restenosis vs bare metal stent (BMS) restenosis. METHODS AND RESULTS: The 252 in-stent restenosis (ISR) lesions in 224 consecutive patients treated by CBA (n=167) or PBA (n=85) between July 2002 and December 2007 were analyzed. At 6-month angiographic and 12-month clinical follow-up, CBA and PBA showed similar efficacies: repeat-ISR (37.0% vs 37.8%, P=0.90), late loss (0.62+/-0.60 vs 0.61+/-0.47 mm, P=0.92), and target lesion revascularization (18.3% vs 22.4%, P=0.50). This comparable efficacy was maintained for treatment in the DES-ISR and BMS-ISR subgroups. However, target lesion-related myocardial infarction (n=9) occurred more frequently in the CBA than in the PBA arm (6.2% vs 0%, P=0.03), most of which developed early after ISR treatment (n=7; 54+/-26 days). Independent predictors of repeat-ISR were diffuse ISR and smaller pretreatment minimal lumen diameter, both of which might imply heavier plaque burden in the ISR group. CONCLUSIONS: Plain or cutting balloon angioplasty for ISR seems to be comparable, as the angiographic or clinical endpoints were not affected by initial stent type but by parameters related to the plaque burden of the ISR lesion. However, CBA might be associated with higher risk of myocardial infarction than PBA, suggesting more attention to dual-antiplatelet therapy after its use for ISR.

Clinical significance of incidentally detected aneurysms of the membranous ventricular septum in adults by multidetector computed tomography.

Although the clinical relevance of aneurysm of the membranous ventricular septum (AMVS) in adults is unclear, the frequency of AMVS detection has been increased because cardiac multidetector computed tomography has been widely adopted for the evaluation of coronary artery disease. Therefore, we aimed to assess the clinical significance of AMVS in a longitudinal study. In 30,120 adults with suspected coronary artery disease who underwent cardiac multidetector computed tomography in 3 hospitals, 52 patients with AMVS were retrospectively selected. We evaluated the clinical symptoms and electrocardiographic abnormalities (cross-sectional study) and the prevalence of embolic stroke (observational study) during a median 40-month (range 6 to 74 months) observation period. For the assessment of embolic stroke, we excluded 9 patients with other explainable embolic sources. Conduction abnormalities were noted in 13 of 52 adults (25%) with AMVS on electrocardiography and embolic stroke occurred in 6 of 43 patients (14%). The mean age and the prevalence of hypertension were significantly higher in the embolic stroke group than in the event-free group (p <0.05). Thrombi were detected in the 11.6% of AMVS, which was significantly related with embolic stroke (p <0.05). The size and morphology did not change in 15 patients with serial follow-up images. In conclusion, our study suggests that AMVS in adults should not be ignored because AMVS may be related to conduction abnormality or embolic stroke, and it does not spontaneously resolve or diminish in size.

Assessment of the efficacy and tolerability of 2 formulations of atorvastatin in Korean adults with hypercholesterolemia: a multicenter, prospective, open-label, randomized trial.

BACKGROUND: A manufacturer of atorvastatin is seeking marketing approval in Korea of a generic product for adult patients with primary hypercholesterolemia. OBJECTIVE: The objective of this study was to compare the efficacy and tolerability of a new generic formulation of atorvastatin (test) with those of an original formulation of atorvastatin (reference) to satisfy regulatory requirements for marketing of the generic product in Korea. METHODS: Patients enrolled were aged 20 to 79 years with documented primary hypercholesterolemia who did not respond adequately to therapeutic lifestyle changes and with a LDL-C level >100 mg/dL from a high-risk group of coronary artery disease patients. Eligible patients were randomized to receive 1 of the 2 formulations of atorvastatin 20 mg per day for 8 weeks. The primary end point was the percent change in LDL-C level from baseline to week 8. Secondary end points included the percent change in total cholesterol, triglycerides, HDL-C level, apolipoprotein B:apolipoprotein A-I ratio, LDL:HDL ratio, LDL-C particle size, high-sensitivity C-reactive protein from baseline to week 8, and achievement rate of the LDL-C goal. RESULTS: A total of 298 patients (141 men and 157 women; 149 patients in each group; mean [SD] age, 62.4 [9.2] in the test group vs 60.3 [8.9] years in the reference group) were included. LDL-C levels were significantly decreased from baseline to week 8 in both groups, and there was no significant difference in the percent change in LDL-C level between groups (-44.0% [17.2%] in the test group, -45.4% [16.9%] in the reference group; P = 0.49). The between-group differences in the percent changes in total cholesterol and triglyceride levels were not statistically significant. In addition, there was no significant difference between the 2 groups in percent changes in HDL-C, apolipoprotein B:apolipoprotein A-I ratio, LDL-C:HDL-C ratio, LDL-C particle size, high-sensitivity C-reactive protein, and the achievement rate of the LDL-C goal. Two (1.3%) patients in the reference group (N = 150) experienced treatment-related serious adverse events (AEs): toxic hepatitis and aggravation of chest pain. Common AEs were cough (4.1%), myalgia (2.1%), and indigestion (1.4%) in the test formulation group and cough (5.3%), creatine kinase elevation (2.7%), and edema (0.7%) in the reference formulation group; however, the differences in overall prevalence of AEs between the 2 treatment groups was not significant (P = 0.88). CONCLUSIONS: There were no significant differences observed in the efficacy and tolerability between the test and reference formulations of atorvastatin in these Korean adult patients with primary hypercholesterolemia.

Electrocardiographic QRS duration reflects right ventricular remodeling in patients undergoing corrective surgery for isolated tricuspid regurgitation: a comparative study with cardiac magnetic resonance imaging.

BACKGROUND: The role of electrocardiogram (ECG) is unclear for the longitudinal follow-up of patients who undergo corrective surgery for isolated severe tricuspid regurgitation (TR). HYPOTHESIS: This study sought to investigate the usefulness of changes in QRS duration of ECG after TR surgery in predicting right ventricular (RV) reverse remodeling as determined by cardiac magnetic resonance imaging (CMR). METHODS: We enrolled 30 consecutive TR patients (27 women, aged 57.8 ± 9.6 years) who had undergone prior left-sided valve surgery. A computer-assisted analysis was performed for objective calculation of QRS duration before and after surgery. RESULTS: At a median CMR follow-up of 27.5 months postsurgery, QRS duration was cut by 14.6%, from 110.4 ± 14.6 msec to 96.9 ± 11.9 msec (P < 0.001), while CMR showed a decrease in RV end-diastolic volume index (RV-EDVI) from 179.5 ± 59.7 to 119.1 ± 30.4 mL/m(2) (P < 0.001). QRS duration correlated significantly with RV-EDVI and RV end-systolic volume index (r = 0.65, P < 0.001 and r = 0.53, P < 0.001, respectively), and a percent change in QRS duration was significantly correlated with a percent change in RV-EDVI (r = 0.40, P = 0.03). When significant RV reverse remodeling was defined as a reduction in RV-EDVI ≥20% following TR surgery, the sensitivity and specificity for significant RV reverse remodeling were 75% and 78%, respectively, with a 9% reduction in QRS duration (P = 0.01, area underneath the receiver operator curve [AUC] = 0.81). CONCLUSIONS: The extent of changes in postoperative QRS duration can be used as a useful, inexpensive, and simple index reflecting the occurrence of significant RV reverse remodeling in patients undergoing corrective TR surgery.

Comparison of hyperemic efficacy between central and peripheral venous adenosine infusion for fractional flow reserve measurement.

BACKGROUND: Maximal hyperemia is a prerequisite for the accurate measurement of fractional flow reserve (FFR). Although continuous infusion of adenosine via the femoral vein is considered to be the gold standard, this requires an additional invasive procedure for femoral vein access and is difficult to use during transradial coronary catheterization. We performed this prospective study to evaluate the feasibility and efficacy of peripheral intravenous infusion of adenosine for FFR measurement. METHODS AND RESULTS: Seventy-one patients were prospectively enrolled, and FFR was measured using a 0.014-inch coronary pressure wire. Hyperemic efficacy of adenosine was compared among intracoronary bolus injection and continuous IV infusion (140 µg/min/kg) via the femoral and via the forearm vein. In 20 patients, hyperemic mean transit time and index of microcirculatory resistance were also measured. Mean FFR after bolus administration of adenosine was 0.81±0.10. As compared with femoral vein infusion (FFR: 0.80±0.10), hyperemic efficacy of forearm vein infusion of adenosine (FFR: 0.80±0.11) was not inferior (P for noninferiority=0.01). The number of functionally significant stenoses (FFR <0.75) was also not different between the 2 methods (femoral vein versus forearm vein; 17 (25.0%) versus 17 (25.0%), P=1.0). Both hyperemic mean transit time and index of microcirculatory resistance were not different between the 2 routes of adenosine infusion. Additional bolus injection of adenosine during IV infusion did not improve the hyperemic efficacy but increased the risk of atrioventricular block. CONCLUSIONS: This study suggests that continuous intravenous infusion of adenosine via the forearm vein is a convenient and effective way to induce steady-state hyperemia for invasive physiological measurements. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01070420.

Synchronicity of LV contraction as a determinant of LV twist mechanics: serial speckle-tracking analyses in WPW syndrome before and after radiofrequency catheter ablation.

OBJECTIVES: This study set out to investigate the isolated impact of synchronous patterns of left ventricular (LV) contraction (i.e., LV synchronicity) on LV twist behavior. BACKGROUND: Although the relationships between LV loading status/LV contractility and twist are well-established, no data are available regarding the relation between LV twist and LV synchronicity, without any interference by changes in LV pre-load, afterload, and contractility. Serial assessment of patients with Wolff-Parkinson-White syndrome before and after radiofrequency catheter ablation (RFCA) allows this to be explored. METHOD: Of the 40 Wolff-Parkinson-White patients initially screened, 34 were enrolled. Two-dimensional and Doppler echocardiography along with speckle tracking-derived LV twist mechanics, apical-basal rotation delay, and left ventricular dyssynchrony index (LVdys) were obtained before and after RFCA. The LVdys was defined as the maximal delay in time-to-peak radial strain of different LV segments at the papillary muscle level. RESULTS: Overall, no significant changes were demonstrated in LV volumes, systolic and diastolic function, and end-systolic wall stress before versus after RFCA. After RFCA, median value of LVdys was attenuated from 33.5 (interquartile range [IQR]: 14.0 to 84.3) to 14.0 (IQR: 11.5 to 21.8) (p = 0.002), which was accompanied by a reduction in apical-basal rotation delay from 9.7% (IQR: 3.5 to 23.7) to 3.3% (IQR: 1.3 to 8.0) (p = 0.004). In contrast, LV twist increased from 14.2° (IQR: 9.1° to 18.4°) before to 19.7° (IQR: 15.0° to 22.6°) after RFCA (p = 0.002). Delta LV twist pre- to post-RFCA displayed a significant inverse correlation with changes in apical-basal rotation delay (r = -0.42, p = 0.01) and Delta LVdys (r = -0.39, p = 0.02). CONCLUSIONS: The LV synchronous contraction is significantly related to LV twist.

Beneficial Effect of Efonidipine, an L- and T-Type Dual Calcium Channel Blocker, on Heart Rate and Blood Pressure in Patients With Mild-to-Moderate Essential Hypertension.

BACKGROUND AND OBJECTIVES: Efonidipine hydrochloride, an L- and T-type dual calcium channel blocker, is suggested to have a heart rate (HR)-slowing action in addition to a blood pressure (BP)-lowering effect. The aim of this study was to determine the effect of efonidipine on HR and BP in patients with mild-to-moderate hypertension. SUBJECTS AND METHODS: In a multi-center, prospective, open-labeled, single-armed study, we enrolled 53 patients who had mild-to-moderate hypertension {sitting diastolic BP (SiDBP) 90-110 mmHg}. After a 2-week washout, eligible patients were treated with efonidipine (40 mg once daily for 12 weeks). The primary end point was the change in HR from baseline to week 12. The secondary end-point included the change in trough sitting BP and 24-hour mean BP between baseline and week 12. Laboratory and clinical adverse events were monitored at each study visit (4, 8, and 12 weeks). RESULTS: Fifty-two patients were included in the intention-to-treat analysis. After 12 weeks of treatment with efonidipine, the resting HR decreased significantly from baseline to week 12 {from 81.5±5.3 to 71.8±9.9 beats/minute (difference, -9.9±9.0 beats/minute), p<0.0001}. The trough BP {sitting systolic blood pressure (SiSBP) and SiDBP} and 24-hour mean BP also decreased significantly (SiSBP: from 144.6±8.2 to 132.9±13.5 mmHg, p<0.0001; SiDBP: from 96.9±5.4 to 88.3±8.6 mmHg, p<0.0001, 24-hour mean systolic BP: from 140.4±13.5 to 133.8±11.6 mmHg, p<0.0001; 24-hour mean diastolic BP: from 91.7±8.7 to 87.5±9.5 mmHg, p<0.0001). CONCLUSION: Efonidipine was effective in controlling both HR and BP in patients with mild-to-moderate hypertension.

Impact of loading condition on the 2D speckle tracking-derived left ventricular dyssynchrony index in nonischemic dilated cardiomyopathy.

BACKGROUND: The effects of left ventricular (LV) loading conditions on LV dyssynchrony have not been elucidated. We modified LV loading conditions to reveal their effects on echocardiography-derived LV dyssynchrony index (LVdys) in patients with documented nonischemic dilated cardiomyopathy. METHODS AND RESULTS: Thirty-seven patients were consecutively enrolled. After baseline measurements, pneumatic compression of the lower extremities (Pcom) was used to increase LV afterload. Subsequently, sublingual nitroglycerin (SL-NG) was administered to modify preload. Conventional echocardiographic parameters, LVdys (by speckle-tracking radial strain analysis) and LV end-systolic wall stress (LV-ESWS), were calculated under each condition. LVdys-6 (defined as the maximal difference in time-to-peak radial strain between 6 myocardial segments) and LV-ESWS increased under Pcom (for LVdys-6, 159+/-117 at baseline versus 239+/-140 ms under Pcom, P<0.05; for LV-ESWS, 191+/-63 versus 228+/-80 g/m(2), P<0.05) After SL-NG application, both parameters decreased significantly (for LVdys-6, 239+/-140 under Pcom versus 147+/-103 ms after SL-NG, P<0.05; for LV-ESWS, 228+/-80 under Pcom versus 189+/-67 g/m(2) after SL-NG, P<0.05). When the presence of LV dyssynchrony was defined as the absolute difference in time-to-peak radial strain between the anteroseptal and posterior segments (LVdys-2), the results were unchanged. Using 130 ms as a cutoff value, the proportion of patients with LV dyssynchrony changed significantly (29.7% at baseline, 45.9% under Pcom, and 35.1% after SL-NG). When the presence of LV dyssynchrony was defined as standard deviation of the time to peak radial strain for 6 segments (LVdys-SD), the results were same. LVdys and LV-ESWS showed a modest but significant association with each other (r=0.47, P<0.001 for LVdys-6; r=0.41, P<0.001 for LVdys-2; r=0.46, P<0.001 for LVdys-SD). CONCLUSIONS: To the best of our knowledge, the present study provides the first evidence of a significant association between LVdys and LV loading status, reflective of a dynamic nature of LVdys. Accordingly, LV loading conditions should be taken into account when echocardiographic LVdys is used for clinical decision-making of selecting candidates for cardiac resynchronization therapy or when it is used as a surrogate marker of prognosis.

Implantable cardioverter-defibrillator implantation in a patient with atrial standstill.

We report a 55-year-old female patient who presented with no P waves but with a wide QRS complex escape rhythm at 44 beats/min and prolonged QTc of 0.55 seconds on ECG. The patient had recurrence of ventricular fibrillations and loss of consciousness, and underwent defibrillation and cardiopulmonary resuscitation (CPR) several times because of cardiac arrest. The transthoracic echocardiography showed dilated cardiomyopathy and enlargement of both atria. The Doppler echocardiography documented the absence of A wave in the tricuspid and mitral valve flow. An electrophysiologic study demonstrated electrical inactivity in the right and left atria. Atrial pacing with maximum output did not capture the atria. These findings together with her electrocardiographic finding indicated atrial standstill. Sudden cardiac death was her first clinical manifestation of ventricular arrhythmia. The patient remained asymptomatic after receiving a single chamber implantable cardioverter-defibrillator (ICD) with VVI pacemaker function.

Randomized comparison of adjunctive cilostazol versus high maintenance dose clopidogrel in patients with high post-treatment platelet reactivity: results of the ACCEL-RESISTANCE (Adjunctive Cilostazol Versus High Maintenance Dose Clopidogrel in Patients With Clopidogrel Resistance) randomized study.

OBJECTIVES: The purpose of this study was to determine the impact of adjunctive cilostazol in patients with high post-treatment platelet reactivity (HPPR) undergoing coronary stenting. BACKGROUND: Although addition of cilostazol to dual antiplatelet therapy enhances adenosine diphosphate (ADP)-induced platelet inhibition, it is unknown whether adjunctive cilostazol can reduce HPPR. METHODS: Sixty patients with HPPR after a 300-mg loading dose of clopidogrel were enrolled. HPPR was defined as maximal platelet aggregation (Agg(max)) >50% with 5 micromol/l ADP. Patients were randomly assigned to receive either adjunctive cilostazol (triple group; n = 30) or high maintenance dose (MD) clopidogrel (high-MD group; n = 30). Platelet function was assessed at baseline and after 30 days with conventional aggregometry and the VerifyNow assay. RESULTS: Baseline platelet function measurements were similar in both groups. After 30 days, significantly fewer patients in the triple versus high-MD group had HPPR (3.3% vs. 26.7%, p = 0.012). Percent inhibitions of 5 micromol/l ADP-induced Agg(max) and late platelet aggregation (Agg(late)) were significantly greater in the triple versus high-MD group (51.1 +/- 22.5% vs. 28.0 +/- 18.5%, p < 0.001, and 70.9 +/- 27.3% vs. 45.3 +/- 23.4%, p < 0.001, respectively). Percent inhibitions of 20 micromol/l ADP-induced Agg(max) and Agg(late) were consistently greater in the triple versus high-MD group. Percent change of P2Y12 reaction units demonstrated a higher antiplatelet effect in the triple versus high-MD group (39.6 +/- 24.1% vs. 23.1 +/- 29.9%, p = 0.022). CONCLUSIONS: Adjunctive cilostazol reduces the rate of HPPR and intensifies platelet inhibition as compared with a high-MD clopidogrel of 150 mg/day.