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.     

Effect of biventricular pacing on metabolism and perfusion in patients affected by dilated cardiomyopathy and left bundle branch block: evaluation by positron emission tomography.

AIMS: Evaluate the possible changes in myocardial metabolism and perfusion induced by biventricular pacing (BIVP) in patients affected by dilated cardiomyopathy (DC) and left bundle branch block (LBBB). METHODS AND RESULTS: Eight male patients (aged 60-79 years, mean 69) affected by DC (NYHA functional class III and ejection fraction <40%) were submitted to cardiac PET in basal condition and 3 weeks after the implantation of a biventricular device. Metabolism was evaluated using F18-fluorodeoxyglucose (FDG), by the glucose load-insulin technique, and perfusion by N13-ammonia (NH3), injected at rest. Visual and a semi quantitative analyses were performed, calculating by ROIs the septum to lateral uptake ratio (SLR). The myocardial blood flow (MBF) was also calculated in ml/min/g using a dynamic acquisition and a modified Patlak method. In all 8 patients a selective defect in FDG uptake in the septum was present in basal condition (mean SLR 0.59+/-0.17) with a 'reverse mismatch' effect with respect to NH3 (mean SLR 1.07+/-0.18). During BIVP the distribution of FDG in the septal area significatively improved (mean SLR 0.86+/-0.15 P=0.011 with respect to basal); on the contrary, no significant changes were found in NH3 uptake (mean SLR 1.02+/-0.23, P=ns).On quantitative analysis the mean MBF in the septum was 1.05+/-0.37 in basal condition and did not significantly change during BIVP (0.95+/-0.34, P=0.06). CONCLUSIONS: Our results suggest that, in patients affected by DC and LBBB, BIVP improves the septal glucose metabolism without significant changes in myocardial perfusion.     

Cardioprotective effects of trimetazidine on patients with dilated cardiomyopathy and left bundle branch block

Background The effects of trimetazidine on patients with dilated cardiomyopathy(DCM) and left bundle branch block(LBBB) are not clear. Methods Sixty consecutive patients with DCM, LBBB and heart dysfunction(35% ≤ LVEF ≤ 45%) were randomly allocated to heart failure therapy plus trimetazidine group(20 mg three times a day; 30 patients) or heart failure therapy alone group(30 patients). During follow-up of 6months, QRS morphology, plasma NT-proBNP, 6-minute walk test(6MWT) and echocardiographic indexes were measured. Results At the 6th month, a significant functional improvement was noted in patients receiving trimetazidine added to heart failure treatment. In patients from the trimetazidine group, an increase of left ventricular ejection fraction(LVEF) was noted(from 38 ± 5.5% to 47 ± 7.1%, P = 0.020). The increase of LVEF in the trimetazidine group was associated with a more significant reduction of the left ventricular endsystolic diameter(LVESD) compared with the control group at 6-month follow-up. The NT-pro BNP levels decreased significantly in the trimetazidine group(3.11 ± 0.47 at baseline and 2.77 ± 0.45 at 6-month followup, P 0.01) and the 6MWT increased significantly in the trimetazidine group(325 ± 44 m at baseline and419 ± 56 m at 6-month follow-up, P 0.01). The differences in NT-pro BNP levels(2.77 ± 0.45 vs 2.96 ±0.46, P = 0.036) and 6MWT(419 ± 56 m vs 366 ± 54 m, P = 0.032) between the two groups were significant at 6-month follow-up. Conclusions Trimetazidine can improve LV function caused by DCM and LBBB. The positive effects of trimetazidine on LV function are especially evident in patients with optimization of drug therapy for heart failure, which strongly suggests an additive effect of these therapy modalities.     

Distinct left bundle branch block pattern in ischemic and non-ischemic dilated cardiomyopathy

BACKGROUND: A high percentage of patients with dilated cardiomyopathy have the electrocardiographic (ECG) pattern of advanced left bundle branch block (LBBB). In the present study we sought to investigate whether patients with dilated cardiomyopathy of ischemic or non-ischemic etiology can be differentiated on the basis of LBBB pattern. METHODS AND RESULTS: The study population included 41 patients with dilated cardiomyopathy of non-ischemic (NIC) (n=26) or ischemic origin (IC) (n=15) and LBBB on surface ECG. ECG duration and voltage were digitally measured. The presence of notching of S wave in right precordial leads (V1-V3) was not statistically different between the groups. The voltages of precordial leads V2, V3 and the Sigma(V1+V2+V3 voltages) were significantly more prominent in patients with NIC (P=0.002, P<0.001 and P=0.002, respectively). The discriminative power of receiver operating characteristic analysis was best at voltages of V3 of 2100 microV (area under the curve, 0.805; standard error, 0.001). The sensitivity and specificity of V3 voltage >2100 microV on surface ECG in the presence of LBBB to identify a cardiomyopathy of non-ischemic origin were 85 and 73%, respectively. CONCLUSIONS: A single ECG criteria, voltage of lead V3, appears to be a useful parameter to identify patients with dilated cardiomyopathy of ischemic or non-ischemic origin in the presence of advanced LBBB.     

Improved specificity of myocardial thallium-201 single-photon emission computed tomography in patients with left bundle branch block by dipyridamole

Reduced septal uptake of thallium-201 during exercise is frequently observed in patients with left bundle branch block (LBBB) and normal coronary arteries. This may reflect normal coronary autoregulation in response to lower septal oxygen demand; thus, dipyridamole, which uniformly exploits flow reserve, would be more accurate for diagnosis of coronary artery disease (CAD). Sixteen patients with LBBB underwent exercise and dipyridamole thallium-201 single-photon emission computed tomography and coronary angiography within 3 months. Sensitivity for detection of left anterior descending CAD (greater than 50% stenosis) was 0.83 for exercise and 1.00 for dipyridamole. Specificity was 0.30 (visual) or 0.20 (quantitative analysis) for exercise and 0.80 (visual) or 0.90 (quantitative) for dipyridamole (p less than 0.05). Dipyridamole combined with quantitative analysis also improved specificity of CAD detection overall (p less than 0.01). These data demonstrate that pharmacologic vasodilation is more accurate than exercise when diagnosing CAD by myocardial perfusion scintigraphy in patients with LBBB.     

His束起搏治疗扩张型心肌病伴完全性左束支阻滞患者的心力衰竭(附二例报道)

2例均为扩张型心肌病合并完全性左束支传导阻滞(CLBBB),NYHA心功能Ⅲ级,在接受心脏再同步化过程中,左室电极不能到达靶静脉,改用His束起搏治疗。1例57岁男性患者,随访10个月,临床症状明显改善,QRS波恢复正常,左室及左室射血分数恢复正常。另1例50岁的男性患者,随访12个月,临床症状明显改善,QRS波恢复正常,左室及左室射血分数恢复正常。     

Effect of left bundle branch block on diastolic function in dilated cardiomyopathy.

OBJECTIVE--To assess the diastolic effect of left bundle branch block in patients with dilated cardiomyopathy. DESIGN--Retrospective study of M mode and Doppler echocardiograms along with electrocardiogram and phonocardiogram. SETTING--Tertiary referral cardiac centre. PATIENT PARTICIPANTS--Fifty two patients with dilated cardiomyopathy, all with functional mitral regurgitation. Twelve with left bundle branch block (group 1) were compared with 40 without (group 2). RESULTS--Mean (SD) age 60 (15) v 55 (18) years, left ventricular end diastolic dimension 72 (9) v 70 (7) mm, and heart rate 88 (15) v 84 (15) beats/min were similar in both groups. In patients with left bundle branch block the electromechanical delay, 50 (20) v 70 (20) ms, was shorter (p less than 0.05) whereas the preejection contraction time, measured from the onset of mitral regurgitation to that of aortic ejection, 130 (40) v 70 (20) ms (p less than 0.01), and left ventricular relaxation time, A2 to the end of mitral regurgitation, 130 (30) v 80 (30) ms (p less than 0.01), were both prolonged. Ejection time itself was similar, 230 (40) v 235 (40) ms. Thus the overall duration of mitral regurgitation was increased (495 (90) v 390 (60) ms (p less than 0.01], which made filling time shorter (190 (45) v 325 (90) ms (p less than 0.01]. In patients with left bundle branch block, unlike those without, contraction and relaxation times both shortened as RR interval fell; this made the duration of mitral regurgitation more sensitive to heart rate. Filling time was less than 200 ms in eight out of 12 patients with left bundle branch block and four out of 40 patients without (p less than 0.001). CONCLUSION--Left bundle branch block prolongs rather than delays mitral regurgitation by increasing pre-ejection and relaxation times. This directly impairs diastolic function by shortening the time available for the left ventricule to fill to an extent likely to limit stroke volume.     

Effect of left bundle branch block on diastolic function in dilated cardiomyopathy.

OBJECTIVE--To assess the diastolic effect of left bundle branch block in patients with dilated cardiomyopathy. DESIGN--Retrospective study of M mode and Doppler echocardiograms along with electrocardiogram and phonocardiogram. SETTING--Tertiary referral cardiac centre. PATIENT PARTICIPANTS--Fifty two patients with dilated cardiomyopathy, all with functional mitral regurgitation. Twelve with left bundle branch block (group 1) were compared with 40 without (group 2). RESULTS--Mean (SD) age 60 (15) v 55 (18) years, left ventricular end diastolic dimension 72 (9) v 70 (7) mm, and heart rate 88 (15) v 84 (15) beats/min were similar in both groups. In patients with left bundle branch block the electromechanical delay, 50 (20) v 70 (20) ms, was shorter (p less than 0.05) whereas the preejection contraction time, measured from the onset of mitral regurgitation to that of aortic ejection, 130 (40) v 70 (20) ms (p less than 0.01), and left ventricular relaxation time, A2 to the end of mitral regurgitation, 130 (30) v 80 (30) ms (p less than 0.01), were both prolonged. Ejection time itself was similar, 230 (40) v 235 (40) ms. Thus the overall duration of mitral regurgitation was increased (495 (90) v 390 (60) ms (p less than 0.01], which made filling time shorter (190 (45) v 325 (90) ms (p less than 0.01]. In patients with left bundle branch block, unlike those without, contraction and relaxation times both shortened as RR interval fell; this made the duration of mitral regurgitation more sensitive to heart rate. Filling time was less than 200 ms in eight out of 12 patients with left bundle branch block and four out of 40 patients without (p less than 0.001). CONCLUSION--Left bundle branch block prolongs rather than delays mitral regurgitation by increasing pre-ejection and relaxation times. This directly impairs diastolic function by shortening the time available for the left ventricule to fill to an extent likely to limit stroke volume.     

Positron emission tomography is a useful tool in differentiating idiopathic from ischemic dilated cardiomyopathy

We evaluated the utility of positron emission tomography in differentiating patients with idiopathic dilated cardiomyopathy from those with ischemic cardiomyopathy. Twenty consecutive non-diabetic patients with dilatation (end-diastolic volume > or = 120 cc/m2) and reduced systolic function (ejection fraction < or = 40%) of the left ventricle on cineangiography, underwent coronary angiography, F18 fluorodeoxyglucose (F18-FDG) (glucose load technique) and N13-ammonia (N13-NH3) positron emission tomography. A semiquantitative score based on the extension and the severity of the uptake defects was calculated. Endomyocardial biopsy was performed in patients with normal coronary arteries. Ten patients (group A) had normal coronary arteries and histologic features of the endomyocardium fitting with the diagnosis of idiopathic dilated cardiomyopathy. Cineangiography showed critical stenosis of at least one major coronary artery in the other 10 patients (group B). The two groups were similar in age. left ventricular end-diastolic volume and ejection fraction. Both N13-NH3, positron emission tomography and F18-FDG positron emission tomography scores were lower in group A than in group B: 0.1 +/- 0.3 vs. 10.6 +/- 5.1 (P<0.0001) and 2.4 +/- 4.4 vs. 9.9 +/- 4.1 (P<0.0001) respectively. but only N13-NH3 positron emission tomography allowed a complete separation of the two groups (score range 0-1 group A vs. 4-12 group B). The F18-FDG score value showed some overlapping between the two groups (score range 0-12 in the group A vs. 2-17 in the group B). All three idiopathic dilated cardiomyopathy patients with a F18-FDG score value >2 had left bundle branch block on standard ECG. Positron emission tomography imaging with N13-NH3 and F18-FDG provided a complete differentiation between idiopathic dilated cardiomyopathy and ischemic cardiomyopathy patients. However patients with left bundle branch block on ECG could present defects in FDG uptake even if affected by idiopathic dilated cardiomyopathy.     

Positron emission tomography scanning in the assessment of patients with lymphoma

BACKGROUND: The detection of lymphoma by computed tomography (CT) scanning is known to be improved by positron emission tomography (PET) and/or gallium scanning, although the direct comparative accuracy of these imaging modalities remains a subject of ongoing review. AIMS: The aim of the present study was to compare PET scanning with conventional imaging (CT and/or gallium scanning) in patients with lymphoma. METHODS: A retrospective study of 38 patients (25 men; 13 women; median age 39.5 years; range 18.0-81.0 years) who had had PET scans (24 scans at initial staging and 46 scans at restaging, including suspected disease relapse) was carried out. Thirty-one concurrent gallium scans had been performed. Disease was validated with clinical follow up or biopsy. RESULTS: The sensitivities of PET and CT at initial staging were 96 and 71%, respectively. PET identified additional sites of disease compared with CT in 29% of patients. Of the 15 patients who had had all three imaging modalities, the sensitivities of PET, CT and gallium were 93, 67 and 87%, respectively. At treatment completion, the positive predictive values of PET, CT and gallium scans for relapse given a residual mass were 100, 33 and 0%, respectively (P = 0.006 for PET and CT comparison). The negative predictive values of PET, CT and gallium were 76, 0 and 70%, respectively (P-value not significant). In suspected disease relapse, PET results changed management in 50% of patients. CONCLUSION: Compared with CT and gallium scans, PET has superior accuracy in staging and restaging, and its greatest value lies in its positive predictive value for relapse in patients with residual masses.     

Diagnostic accuracy of exercise thallium-201 single-photon emission computed tomography in patients with left bundle branch block

Recent reports have proposed that abnormal apical or anterior wall perfusion with exercise thallium-201 imaging may increase diagnostic accuracy for disease of the left anterior descending artery in patients with left bundle branch block (LBBB). To evaluate these suggestions, 83 patients with LBBB who underwent thallium-201 single-photon emission computed tomography and coronary angiography within an interval of 3 months were retrospectively reviewed. There were 59 men and 24 women aged 33 to 84 years (mean 65). Myocardial perfusion to the apex, anterior wall and anterior septum were scored qualitatively by consensus of 2 experienced observers and by quantitative analysis in comparison with a normal data base. The sensitivity, specificity and accuracy of perfusion defects in these segments were then expressed according to angiographic findings. Significant stenosis of vessels within the left anterior descending artery territory was present in 38 patients. By receiver-operator characteristic analysis, a fixed or reversible defect within the apex by the qualitative method was the best criterion for coronary artery disease. However, although highly sensitive (79 and 85% by the qualitative and quantitative methods, respectively), an apical defect was neither specific (38 and 16%, respectively), nor accurate (57 and 46%, respectively). Perfusion abnormalities in the anterior wall and septum were also of limited diagnostic accuracy. Thus, modified interpretative criteria in patients with LBBB are not clinically useful in the assessment of left anterior descending artery disease.     

Diagnosing acute myocardial infarction in patients with left bundle branch block

We compared the clinical features, laboratory and coronary angiographic findings, treatments, and outcomes among patients with ST-segment elevation myocardial infarction (MI) with and without left bundle branch block (LBBB). We examined 5,742 patients with ST-segment elevation MI with and without LBBB treated with primary percutaneous coronary intervention in the Assessment of Pexelizumab in Acute Myocardial Infarction trial. The main outcome measures were obstructive coronary disease, MI, positive cardiac biomarkers, angiographic Thrombolysis In Myocardial Infarction flow, and death, MI, or congestive heart failure at 90 days. LBBB was present in 98 patients (1.7%). According to the protocol, patients with LBBB were eligible only if they had ≥1 mm concordant ST-segment elevation. Obstructive coronary artery disease was present in >87% of the patients with LBBB. Documented MI (elevated biomarkers) with an initially occluded infarct artery was more common in patients with LBBB with concordant ST-segment elevation (71.4%) than in patients without (44.1%; p = 0.027). The use of ST-segment elevation concordance criteria in the presence of LBBB was more often associated with documented MI with an identifiable culprit vessel with an initially occluded infarct-related artery. In conclusion, because a substantial proportion of patients with LBBB have acute MI with a culprit lesion and positive biomarkers, these data support immediate catheterization with the intent for primary percutaneous coronary intervention for all patients presenting with suspected ST-segment elevation myocardial infarction, ischemic symptoms, and presumed new LBBB, particularly if concordant ST-segment elevation is present.     

Effects of cardiac resynchronization therapy on myocardial blood flow measured by oxygen-15 water positron emission tomography in idiopathic-dilated cardiomyopathy and left bundle branch block

Regional and global myocardial blood flow and coronary vascular resistance were determined in patients with idiopathic-dilated cardiomyopathy and left bundle branch block before and during cardiac resynchronization therapy (CRT) using oxygen-15 water positron emission tomography. The investigated parameters did not exhibit regional heterogeneity and were not influenced by CRT. This implies that the beneficial effects of CRT do not require additional oxygen demand or regional reallocation of oxidative metabolism.     

Dipyridamole stress myocardial perfusion by computed tomography in patients with left bundle branch block

Background

Functional tests have limited accuracy for identifying myocardial ischemia in patients with left bundle branch block (LBBB).

Objective

To assess the diagnostic accuracy of dipyridamole-stress myocardial computed tomography perfusion (CTP) by 320-detector CT in patients with LBBB using invasive quantitative coronary angiography (QCA) (stenosis ≥ 70%) as reference; to investigate the advantage of adding CTP to coronary computed tomography angiography (CTA) and compare the results with those of single photon emission computed tomography (SPECT) myocardial perfusion scintigraphy.

Methods

Thirty patients with LBBB who had undergone SPECT for the investigation of coronary artery disease were referred for stress tomography. Independent examiners performed per-patient and per-coronary territory assessments. All patients gave written informed consent to participate in the study that was approved by the institution’s ethics committee.

Results

The patients’ mean age was 62 ± 10 years. The mean dose of radiation for the tomography protocol was 9.3 ± 4.6 mSv. With regard to CTP, the per-patient values for sensitivity, specificity, positive and negative predictive values, and accuracy were 86%, 81%, 80%, 87%, and 83%, respectively (p = 0.001). The per-territory values were 63%, 86%, 65%, 84%, and 79%, respectively (p < 0.001). In both analyses, the addition of CTP to CTA achieved higher diagnostic accuracy for detecting myocardial ischemia than SPECT (p < 0.001).

Conclusion

The use of the stress tomography protocol is feasible and has good diagnostic accuracy for assessing myocardial ischemia in patients with LBBB.