Impact of left bundle branch block on myocardial perfusion and metabolism: A positron emission tomography study.

BACKGROUND: Better understanding of pathophysiological changes, induced by left bundle branch block (LBBB), may improve patient selection for cardiac resynchronization therapy (CRT). Therefore, we assessed the effect of LBBB on regional glucose metabolism, 13N-NH3-derived absolute and semiquantitative myocardial blood flow (MBF), and their relation in non-ischemic CRT candidates. METHODS: Twenty-five consecutive non-ischemic patients with LBBB underwent 18F-FDG and resting dynamic 13N-NH3 PET/CT prior to CRT implantation. Regional 18F-FDG uptake, absolute MBF, and late 13N-NH3 uptake were analyzed and corresponding septal-to-lateral wall ratios (SLR) were calculated. Segmental analysis was performed to evaluate "reverse mismatch," "mismatch," and "match" patterns, based on late 13N-NH3/18F-FDG uptake ratios. RESULTS: A significantly lower 18F-FDG uptake was observed in the septum compared to the lateral wall (SLR 0.53 ± 0.17). A similar pattern was observed for MBF (SLR 0.68 ± 0.18), whereas late 13N-NH3 uptake showed a homogeneous distribution (SLR 0.96 ± 0.13). 13N-NH3/18F-FDG "mismatch" and "reverse mismatch" segments were predominantly present in the lateral (52%) and septal wall (61%), respectively. CONCLUSIONS: Non-ischemic CRT candidates with LBBB demonstrate lower glucose uptake and absolute MBF in the septum compared to the lateral wall. However, late static 13N-NH3 uptake showed a homogenous distribution, reflecting a composite measure of altered regional MBF and metabolism, induced by LBBB.

Assessment of wasted myocardial work: a novel method to quantify energy loss due to uncoordinated left ventricular contractions.

Left ventricular (LV) dyssynchrony reduces myocardial efficiency because work performed by one segment is wasted by stretching other segments. In the present study, we introduce a novel noninvasive clinical method that quantifies wasted energy as the ratio between work consumed during segmental lengthening (wasted work) divided by work during segmental shortening. The wasted work ratio (WWR) principle was studied in 6 anesthetized dogs with left bundle branch block (LBBB) and in 28 patients with cardiomyopathy, including 12 patients with LBBB and 10 patients with cardiac resynchronization therapy. Twenty healthy individuals served as controls. Myocardial strain was measured by speckle tracking echocardiography, and LV pressure (LVP) was measured by micromanometer and a previously validated noninvasive method. Segmental work was calculated by multiplying strain rate and LVP to get instantaneous power, which was integrated to give work as a function of time. A global WWR was also calculated. In dogs, WWR by estimated LVP and strain showed a strong correlation (r = 0.94) and good agreement with WWR by the LV micromanometer and myocardial segment length by sonomicrometry. In patients, noninvasive WWR showed a strong correlation (r = 0.96) and good agreement with WWR using the LV micromanometer. Global WWR was 0.09 ± 0.03 in healthy control subjects, 0.36 ± 0.16 in patients with LBBB, and 0.21 ± 0.09 in cardiomyopathy patients without LBBB. Cardiac resynchronization therapy reduced global WWR from 0.36 ± 0.16 to 0.17 ± 0.07 (P < 0.001). In conclusion, energy loss due to incoordinated contractions can be quantified noninvasively as the LV WWR. This method may be applied to evaluate the mechanical impact of dyssynchrony.

Generation of an induced pluripotent stem cell line (SHETi004-A) from a Chinese Han child with left bundle branch block.

Desmin (DES) is an important intermediate filament protein associated with the extrasarcomeric cytoskeleton and cellular function that was first reported to be associated with cardiac conduction disease and cardiomyopathy in 1998. We generated an induced pluripotent stem cell (iPSC) line from the left bundle branch block (LBBB) patient's peripheral blood mononuclear cells using Sendai virus-mediated reprogramming. The iPSCs exhibited stable amplification, expressed pluripotent markers, and spontaneously differentiated into three layers in vitro. Additionally, it showed a normal diploid karyotype and maintained the pathogenic mutation in DES. Hence, the iPSC line provided a platform for exploring LBBB mechanisms associated with DES mutations.

Mutational spectrum in the Ca(2+)--activated cation channel gene TRPM4 in patients with cardiac conductance disturbances.

Very recently, mutations in the TRPM4 gene have been identified in four pedigrees as the cause of an autosomal dominant form of cardiac conduction disease. To determine the role of TRPM4 gene variations, the relative frequency of TRPM4 mutations and associated phenotypes was assessed in a cohort of 160 unrelated patients with various types of inherited cardiac arrhythmic syndromes. In eight probands with atrioventricular block or right bundle branch block--five familial cases and three sporadic cases--a total of six novel and two published TRPM4 mutations were identified. In patients with sinus node dysfunction, Brugada syndrome, or long-QT syndrome, no mutations were found. The novel mutations include six amino acid substitutions and appeared randomly distributed through predicted TRPM4 protein. In addition, eight polymorphic sites including two in-frame deletions were found. Mutations separated from polymorphisms by absence in control individuals and familial cosegregation in some families. In summary, TRPM4 gene mutations appear to play a major role in cardiac conduction disease but not for other related syndromes so far. The phenotypes are variable and clearly suggestive of additional factors modulating the disease phenotype in some patients.

Relationship of age and exercise performance in patients with heart failure: the HF-ACTION study.

BACKGROUND: More than three fourths of patients with heart failure (HF) are 65 years and older, and older age is associated with worse symptoms and prognoses than is younger age. Reduced exercise capacity is a chief HF complaint and indicates poorer prognosis, especially among elderly persons, but the mechanisms underlying functional decline in older patients with HF are largely unknown. METHODS: Baseline cardiopulmonary exercise testing data from the HF-ACTION trial were assessed to clarify age effects on peak oxygen consumption (VO(2)) and ventilation-carbon dioxide production (VE/VCO(2)) slope. RESULTS: Among 2,331 New York Heart Association class II-IV patients with HF, increased age corresponded to decreased peak VO(2) (-0.14 mL kg(-1) min(-1) per year >40 years; P < .0001) and increased VE/VCO(2) slope (0.30 U/y >70 years; P < .0001). In a multivariable model with 34 other potential determinants, age was the strongest independent predictor of peak VO(2) (partial R(2) 0.130, total R(2) 0.392; P < .001) and a significant but relatively weaker predictor of VE/VCO(2) slope (partial R(2) 0.037, total R(2) 0.199; P < .001). Blunted peak heart rate was also a strong predictor of peak VO(2). Although peak heart rate and age were strongly correlated, both were significant independent predictors of peak VO(2) when analyzed simultaneously in a model. Aggregate comorbidity increased significantly with age but did not account for age effects on peak VO(2). CONCLUSIONS: Age is the strongest predictor of peak VO(2) and a significant predictor of VE/VCO(2) slope in the HF-ACTION population. Age-dependent comorbidities do not explain changes in peak VO(2). Age-related changes in cardiovascular physiology, potentially magnified by the HF disease state, should be considered a contributor to the pathophysiology and a target for more effective therapy in older patients with HF.

Combination of cardiac conduction disease and long QT syndrome caused by mutation T1620K in the cardiac sodium channel.

AIMS: The aim of the present study was to elucidate the molecular mechanism underlying the concomitant occurrence of cardiac conduction disease and long QT syndrome (LQT3), two SCN5A channelopathies that are explained by loss-of-function and gain-of-function, respectively, in the cardiac Na+ channel. METHODS AND RESULTS: A Caucasian family with prolonged QT interval, intermittent bundle-branch block, sudden cardiac death, and syncope was investigated. Lidocaine (1 mg/kg i.v.) normalized the prolonged QT interval and rescued bundle-branch block. An SCN5A mutation analysis was performed that revealed a C-to-A mutation at position 4859 (exon 28), predicted to change a highly conserved threonine for a lysine at position 1620. Mutant channels were characterized both in Xenopus oocytes and HEK293 cells. The T1620K mutation remarkably altered the properties of Nav1.5 channels. In particular, the voltage-dependence of the current decay time constants was largely lost. As a consequence, mutant channels inactivated faster than wild-type channels at potentials negative to -30 mV, resulting in less Na+ inward current (loss-of-function), but significantly slower at potentials positive to -30 mV, resulting in an increased Na+ inward current (gain-of-function). Moreover, we found a hyperpolarized shift of steady-state activation and an accelerated recovery from inactivation (gain-of-function). At the same time, channel availability was significantly reduced at the resting membrane potential (loss-of-function). CONCLUSION: We conclude that lysine at position 1620 leads to both loss-of-function and gain-of-function properties in hNav1.5 channels, which may consequently cause in the same individuals impaired impulse propagation in the conduction system and prolonged QTc intervals, respectively.

Dilated cardiomyopathy is associated with reduced expression of the cardiac sodium channel Scn5a.

OBJECTIVE: Dilated cardiomyopathy (DCM) leads to dilation of the cardiac chambers and congestive heart failure. Recent reports have associated mutations in the SCN5A gene, which codes for the major cardiac sodium channel Nav1.5, with DCM. Although DCM is the most common form of cardiomyopathy, no animal studies have established this functional connection. METHODS AND RESULTS: We have produced transgenic mice that ectopically express the transcriptional repressor Snail in heart. These animals display severe DCM, ECG abnormalities, conduction defects, revealed by voltage-sensitive dye imaging, and significantly reduced voltage-gated sodium current as measured by patch clamping. There is a concomitant decrease in expression of the major cardiac sodium channel gene Scn5a, which we show by gene reporter assays and electrophoretic mobility shift assays is a direct target of Snail. CONCLUSIONS: Our findings indicate that a decrease in Scn5a expression and significant reduction in sodium current can result in DCM, and support the hypothesis that some mutations in the human SCN5A gene can lead to DCM.

Population pharmacokinetic and pharmacodynamic analysis of a class IC antiarrhythmic, pilsicainide, in patients with cardiac arrhythmias.

Population pharmacokinetics (PK) of a sodium channel-blocking antiarrhythmic, pilsicainide, was studied using the nonlinear mixed-effects modeling technique in 91 patients with cardiac arrhythmias (80 suspected Brugada syndrome [BrS] and 11 with atrial fibrillation) who received an intravenous infusion of 10 mg of the drug. Population pharmacodynamic (PD) analysis was also performed using an effect compartment model. PD responses were assessed by changes in electrocardiogram (ECG) pattern (BrS-like elevation of ST-segment) and conduction parameters. The final PK model showed that gender (values were 50% lower in women than in men) and creatinine clearance were significant (P < .01) covariates of weight-normalized systemic clearance of pilsicainide. Patients who showed a BrS-like ECG pattern after the drug administration also showed a significantly (P < .01) greater prolongation in His-Purkinje conduction compared to the remaining patients. In conclusion, female gender, renal dysfunction, and the drug-induced BrS-like ECG morphology may be associated with augmented ECG responses to pilsicainide.

Impaired conduction in the bundle branches of mouse hearts lacking the gap junction protein connexin40.

BACKGROUND: Connexin (Cx)40 and Cx45 are the major protein subunits of gap junction channels in the conduction system of mammals. To determine the role of Cx40, we correlated cardiac activation with Connexin distribution in normal and Cx40-deficient mice hearts. METHODS AND RESULTS: Epicardial and septal activation was recorded in Langendorff-perfused adult mice hearts with a 247-point compound electrode (interelectrode distance, 0.3 mm). After electrophysiological measurements, hearts were prepared for immunohistochemistry and histology to determine Connexin distribution and fibrosis. In both wild-type and Cx40-deficient animals, epicardial activation patterns were similar. The right and left ventricular septum was invariably activated from base to apex. Histology revealed a continuity of myocytes from the common bundle to the septal myocardium. Within this continuity, colocalization was found of Cx43 and Cx45 but not of Cx40 and Cx43. Both animals showed similar His-bundle activation. In Cx40-deficient mice, the proximal bundle branches expressed Cx45 only. The absence of Cx40 in the proximal bundles correlated with right bundle-branch block. Conduction in the left bundle branch was impaired as compared with wild-type animals. CONCLUSIONS: Our data show that (1) in mice, a continuity exists between the common bundle and the septum, and (2) Cx40 deficiency results in right bundle-branch block and impaired left bundle-branch conduction.

Left ventricular or biventricular pacing improves cardiac function at diminished energy cost in patients with dilated cardiomyopathy and left bundle-branch block.

BACKGROUND: Left ventricular or biventricular pacing/stimulation can acutely improve systolic function in patients with dilated cardiomyopathy (DCM) and intraventricular conduction delay by resynchronizing contraction. Most heart failure therapies directly enhancing systolic function do so while concomitantly increasing myocardial oxygen consumption (MVO(2)). We hypothesized that pacing/stimulation, in contrast, incurs systolic benefits without raising energy demand. METHODS AND RESULTS: Ten DCM patients with left bundle-branch block (ejection fraction 20+/-3%, QRS duration 179+/-3 ms, mean+/-SEM) underwent cardiac catheterization to measure ventricular and aortic pressure, coronary blood flow, arterial-coronary sinus oxygen difference (DeltaAVO(2)), and MVO(2). Data were measured under sinus rhythm or with left ventricular or biventricular pacing/stimulation at the same heart rate. These results were then contrasted to intravenous dobutamine (n=7) titrated to match systolic changes during LV pacing. Systolic function rose quickly and substantially from LV pacing (18+/-4% rise in arterial pulse pressure, which correlates with cardiac output, and 43+/-6% increase in dP/dt(max); both P<0.01). However, DeltaAVO(2) and MVO(2) declined -4+/-2% and -8+/-6.5%, respectively (both P<0.05). Similar results were obtained with biventricular activation. In contrast, dobutamine raised dP/dt(max) 37+/-6%, accompanied by a 22+/-11% rise in per-beat MVO(2) (P<0.05 versus pacing). CONCLUSIONS: Ventricular resynchronization by left ventricular or biventricular pacing/stimulation in DCM patients with left bundle-branch block acutely enhances systolic function while modestly lowering energy cost. This should prove valuable for treating DCM patients with basal dyssynchrony.

Cardiac resynchronization therapy homogenizes myocardial glucose metabolism and perfusion in dilated cardiomyopathy and left bundle branch block.

OBJECTIVES: We investigated whether cardiac resynchronization therapy (CRT) affects myocardial glucose metabolism and perfusion in dilated cardiomyopathy (DCM) and left bundle branch block (LBBB). BACKGROUND: Patients with DCM and LBBB present with asynchronous left ventricular (LV) activation, leading to reduced septal glucose metabolism. Cardiac resynchronization therapy recoordinates LV activation, but its effects on myocardial glucose metabolism and perfusion remain unknown. METHODS: In 15 patients (10 females; 61 +/- 13 years) with DCM and LBBB (QRS width 165 +/- 15 ms), gated (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET) and technetium-99m ((99m)Tc)-sestamibi single-photon emission computed tomography were performed before and after two weeks of CRT. Uptake of FDG and (99m)Tc-sestamibi was determined in four LV wall areas. Ejection fraction and volumes were calculated from gated PET. RESULTS: Baseline FDG uptake was heterogeneous (p < 0.0001), with lowest uptake in the septal region (56 +/- 12%) and highest uptake in the lateral region (89 +/- 6%). During CRT, septal and anterior increases (p < 0.01) and lateral decreases (p < 0.01) resulted in homogeneously distributed glucose metabolism. Baseline heterogeneity (p < 0.0001) in (99m)Tc-sestamibi uptake was modest (lowest septal 65 +/- 10%; maximum lateral 84 +/- 5%) and also reduced with CRT, although some heterogeneity (p < 0.05) remained. The septal-to-lateral ratio increased with CRT for FDG (0.62 +/- 0.12 to 0.91 +/- 0.26, p < 0.001) and (99m)Tc-sestamibi uptake (0.77 +/- 0.13 to 0.85 +/- 0.16, p < 0.01). The LV end-diastolic and end-systolic volumes decreased from 293 +/- 160 to 272 +/- 158 ml (p < 0.05) and from 244 +/- 164 to 220 +/- 160 ml (p < 0.01), respectively. Ejection fraction increased from 22 +/- 12% to 25 +/- 13% (p < 0.01). CONCLUSIONS: Glucose metabolism is reduced more than perfusion in the septal compared with LV lateral wall in patients with DCM and LBBB. Cardiac resynchronization therapy restores homogeneous myocardial glucose metabolism with less influence on perfusion.

Brugada syndrome: from cell to bedside.

Since its introduction as a new clinical entity in 1992, the Brugada syndrome has attracted great interest because of its high incidence in many parts of the world and its association with high risk for sudden death in infants, children, and young adults. Recent years have witnessed an exponential rise in the number of reported cases and a striking proliferation of articles serving to define the clinical, genetic, cellular, ionic, and molecular aspects of the disease. A consensus report published in 2002 delineated diagnostic criteria for the syndrome. A second consensus conference was held in September 2003. This review provides an in-depth overview of the clinical, genetic, molecular, and cellular aspects of the Brugada syndrome, incorporating the results of the two consensus conferences, and the numerous clinical and basic publications on the subject. The proposed terminology, diagnostic criteria, risk stratification schemes, and device and pharmacologic approach to therapy discussed are based on available clinical and basic studies and should be considered a work-in-progress that will without doubt require fine-tuning as confirmatory data from molecular studies and prospective trials become available.

Global and regional myocardial oxygen consumption and blood flow in severe cardiomyopathy with left bundle branch block.

OBJECTIVE: In patients with dilated cardiomyopathy (DCM), left bundle branch block (LBBB) is a common finding. The characteristic feature is an asynchronous septal wall motion and most frequently a delay of the lateral and/or posterior wall segments. With the onset of cardiac resynchronization therapy, there is a focus on the specific pathophysiology of a LBBB. However, quantitative data on regional myocardial oxygen consumption (MVO(2)) and blood flow (MBF) are missing. METHODS: We studied 31 patients with severe DCM and LBBB (ejection fraction 22.1+/-7.1%) and 14 patients with mild to moderate DCM without LBBB (ejection fraction 46.7+/-7.9%). Global and regional MVO(2) as well as MBF were determined from a dynamic (11)C-acetate positron emission tomography (PET) study. RESULTS: Global MVO(2) and MBF were lower in the DCM group with LBBB than in the control group (P<0.05). Regionally, the LBBB group revealed a higher (P<0.05) MVO(2) and MBF in the lateral wall than in the other walls. The control group did not show significant differences between the myocardial walls and demonstrated a smaller variability of the parameters. CONCLUSION: DCM patients with LBBB exhibit a more heterogeneous distribution of MVO(2) and MBF among the myocardial walls than DCM patients without LBBB. Due to the LBBB associated electromechanical alterations, the highest regional values of MVO(2) and MBF are found in the lateral wall.

A mutant cardiac sodium channel with multiple biophysical defects associated with overlapping clinical features of Brugada syndrome and cardiac conduction disease.

OBJECTIVE: Loss of Na(+) channel function has been implicated in idiopathic ventricular fibrillation (IVF) and Brugada syndrome. We have studied the biophysical properties of an IVF mutation (S1710L) that exhibited an unusual clinical phenotype: rate-dependent bundle branch block without manifestation of Brugada-type ECG pattern. METHODS: The mutant S1710L channels were expressed in mammalian cells and their gating properties, studied using whole-cell patch clamp techniques, were compared with wild-type (WT) and a Brugada syndrome mutant channel T1620M. RESULTS: The S1710L channel exhibited significantly faster macroscopic current decay than WT or T1620M. In addition, S1710L showed a negative shift in the voltage-dependence of fast inactivation and slower recovery from fast inactivation than in WT or T1620M. In addition to the alterations in fast inactivation most commonly observed in Brugada syndrome mutations, S1710L exhibited marked enhancement in slow inactivation and a large positive shift of activation that potentially decreases conduction velocity. CONCLUSIONS: These functional abnormalities may be responsible for the overlapping clinical phenotypes associated with Brugada syndrome and the cardiac conduction defect, a novel cardiac Na(+) channelopathy.

Human SCN5A gene mutations alter cardiac sodium channel kinetics and are associated with the Brugada syndrome.

BACKGROUND: Primary dysrhythmias other than those associated with the long QT syndrome, are increasingly recognized. One of these are represented by patients with a history of resuscitation from cardiac arrest but without any structural heart disease. These patients exhibit a distinct electrocardiographic (ECG) pattern consisting of a persistent ST-segment elevation in the right precordial leads often but not always accompanied by a right bundle branch block (Brugada syndrome). This syndrome is associated with a high mortality rate and has been shown to display familial occurrence. METHODS AND RESULTS: Pharmacological sodium channel blockade elicits or worsens the electrocardiographic features associated with this syndrome. Hence, a candidate gene approach directed towards SCN5A, the gene encoding the alpha-subunit of the cardiac sodium channel, was followed in six affected individuals. In two patients missense mutations were identified in the coding region of the gene: R1512W in the DIII-DIV cytoplasmic linker and A1924T in the C-terminal cytoplasmic domain. In two other patients mutations were detected near intron/exon junctions. To assess the functional consequences of the R1512W and A1924T mutations, wild-type and mutant sodium channel proteins were expressed in Xenopus oocytes. Both missense mutations affected channel function, most notably a 4-5 mV negative voltage shift of the steady-state activation and inactivation curves in R1512W and a 9 mV negative voltage shift of the steady-state activation curve in A1924T, measured at 22 degrees C. Recovery from inactivation was slightly prolonged for R1512W channels. The time dependent kinetics of activation and inactivation at -20 mV were not significantly affected by either mutation. CONCLUSIONS: Two SCN5A mutations associated with the Brugada syndrome, significantly affect cardiac sodium channel characteristics. The alterations seem to be associated with an increase in inward sodium current during the action potential upstroke.

Current concepts relating coronary flow, myocardial perfusion and metabolism in left bundle branch block and cardiac resynchronisation therapy.

Cardiac resynchronisation therapy (CRT) improves mortality and symptoms in heart failure patients with electromechanically dyssynchronous ventricles. There is a 50% non-response rate and reproducible biomarkers to predict non-response have not been forthcoming. Therefore, there has been increasing interest in the pathophysiological effects of dyssynchrony particularly focusing on coronary flow, myocardial perfusion and metabolism. Studies suggest that dyssynchronous electrical activation effects coronary flow throughout the coronary vasculature from the epicardial arteries to the microvascular bed and that these changes can be corrected by CRT. The effect of both electrical and mechanical dyssynchrony on myocardial perfusion is unclear with some studies suggesting there is a reduction in septal perfusion whilst others propose that there is an increase in lateral perfusion. Better understanding of these effects offers the possibility for better prediction of non-response. CRT appears to improve homogeneity in myocardial perfusion where heterogeneity is described in the initial substrate. Novel approaches to the identification of non-responders via metabolic phenotyping both invasively and non-invasively have been encouraging. There remains a need for further research to clarify the interaction of coronary flow with perfusion and metabolism in patients who undergo CRT.

Main clinical determinants of the presence of coronary artery disease in patients with left bundle branch block.

BACKGROUND: Considering clinical parameters as main predictors for coronary artery dis-ease (CAD)in patients with left bundle branch block (LBBB) can be very helpful to explain high likelihood of ischemic events in LBBB conditions. In the present study, we attempted to identify major clinical determinants to predict CAD occurrence in patients with LBBB. METHODS: A retrospective chart review of 229 consecutive patients with the diagnosis of complete LBBB pattern on electrocardiograms was conducted. The final diagnosis of LBBB was based on the Criteria Committee of the New York Heart Association. The participants were also classified based on coronary angiography evidences into two groups including CAD patients (n =99) and non-CAD patients (n =130). RESULTS: Among 99 patients with CAD, 27 (27.3%) had single vessel disease, 30 (30.3%) had two-vessel disease and 42 (42.4%) had three-vessel disease. Also, only two of them had left main lesions. The number of diseased coronary vessels was significantly higher in men than in women so that three vessels disease in men was revealed in 28% and in women was observed in 10.9% (p = 0.002). Using a multivariable logistic regression analysis, male gender (2.445, 95% CI: 1.372-4.367, p = 0.002), advanced age (1.063, 95% CI: 1.032-1.095, p < 0.001), and cigarette smoking (4.112, 95% CI: 1.145-8.635, p = 0.012) were main predictors of CAD in LBBB patients. CONCLUSION: A notable number of patients with LBBB suffered concomitantly from CAD that the presence and severity of this ischemic event could be predicted by male gender, advanced age, and history of smoking in these patients.

Septal and anterior reverse mismatch of myocardial perfusion and metabolism in patients with coronary artery disease and left bundle branch block.

The effects of left bundle branch block (LBBB) on left ventricular myocardial metabolism have not been well investigated. This study evaluated these effects in patients with coronary artery disease (CAD).Sixty-five CAD patients with complete LBBB (mean age, 61.8 ±â€Š9.7 years) and 65 without LBBB (mean age, 59.9 ±â€Š8.4 years) underwent single photon emission computed tomography, positron emission tomography, and contrast coronary angiography. The relationship between myocardial perfusion and metabolism and reverse mismatch score, and that between QRS length and reverse mismatch score and wall motion score were evaluated.The incidence of left ventricular septum and anterior wall reverse mismatching between the two groups was significantly different (P < 0.001 and P = 0.002, respectively). The incidences of normal myocardial perfusion and metabolism in the left ventricular lateral and inferior walls were also significantly different between the two groups (P < 0.001 and P < 0.001, respectively). The incidence of septal reverse mismatching in patients with mild to moderate perfusion was significantly higher among those with LBBB than among those without LBBB (P < 0.001). In CAD patients with LBBB, septal reverse mismatching was significantly more common among those with mild to moderate perfusion than among those with severe perfusion defects (P = 0.002). The correlation between the septal reverse mismatch score and QRS length was significant (P = 0.026).In patients with CAD and LBBB, septal and anterior reverse mismatching of myocardial perfusion and metabolism was frequently present; the septal reverse mismatch score negatively correlated with the QRS interval.