Reversal of primary and pseudo-primary T wave abnormalities by ventricular pacing. A novel manifestation of cardiac memory

Aims  

“Cardiac memory” refers to abnormal T waves (TW) appearing after transient periods of altered ventricular depolarization. The aim of the study was to test the hypothesis that in the presence of abnormal TW, short periods of tailored ventricular pacing (VP) can be followed by normalization of ventricular repolarization.     

Alterations in myostatin expression are associated with changes in cardiac left ventricular mass but not ejection fraction in the mouse

Myostatin (Mst) is a negative regulator of skeletal muscle in humans and animals. It is moderately expressed in the heart of sheep and cattle, increasing considerably after infarction. Genetic blockade of Mst expression increases cardiomyocyte growth. We determined whether Mst overexpression in the heart of transgenic mice reduces left ventricular size and function, and inhibits in vitro cardiomyocyte proliferation. Young transgenic mice overexpressing Mst in the heart (Mst transgenic mice (TG) under a muscle creatine kinase (MCK) promoter active in cardiac and skeletal muscle, and Mst knockout (Mst (-/-)) mice were used. Xiscan angiography revealed that the left ventricular ejection fraction did not differ between the Mst TG and the Mst (-/-) mice, when compared with their respective wild-type strains, despite the decrease in whole heart and left ventricular size in Mst TG mice, and their increase in Mst (-/-) animals. The expected changes in cardiac Mst were measured by RT-PCR and western blot. Mst and its receptor (ActRIIb) were detected by RT-PCR in rat H9c2 cardiomyocytes. Transfection of H9c2 with plasmids expressing Mst under muscle-specific creatine kinase promoter, or cytomegalovirus promoter, enhanced p21 and reduced cdk2 expression, when assessed by western blot. A decrease in cell number occurred by incubation with recombinant Mst (formazan assay), without affecting apoptosis or cardiomyocyte size. Anti-Mst antibody increased cardiomyocyte replication, whereas transfection with the Mst-expressing plasmids inhibited it. In conclusion, Mst does not affect cardiac systolic function in mice overexpressing or lacking the active protein, but it reduces cardiac mass and cardiomyocyte proliferation.     

Functional changes of ventricular late potentials by provocation with increase of heart rate. Evaluation during atrial pacing.

BACKGROUND: Standard methods fail to reveal late potentials in 20 to 30% of patients with ventricular arrhythmias after myocardial infarction. However, these patients may develop transient delayed ventricular activation during increases in heart rate. METHODS AND RESULTS: Atrial pacing was performed, at the rates of 100 min-1 and 120 min-1, in 50 patients after myocardial infarction. Twenty-six patients had a history of documented, sustained ventricular tachycardia, 12 had a history of ventricular fibrillation and 12 no history of ventricular arrhythmias. The low-noise surface electrocardiogram was analysed before and during atrial pacing in the time and frequency domains. Fifteen of 26 patients with ventricular tachycardia, four of 12 with ventricular fibrillation and three of 12 without ventricular arrhythmias experienced late potentials during sinus rhythm. Atrial pacing led to a shift of 26 +/- 15 ms of preexistent late potentials into the ST segment, this being greater in patients with anterior infarctions and to an increase in magnitude in patients with inferior infarctions. In patients without late potentials during sinus rhythm, atrial pacing provoked late potentials in eight of 11 patients with ventricular tachycardia, in four of eight patients with ventricular fibrillation and in one of nine patients without ventricular arrhythmias. Low amplitude signals (LAS) were increased in patients after inferior and filtered QRS in patients after anterior infarction. In 10 patients without cardiac disease no late potentials were detectable in the time and frequency domain either at rest or during increased heart rate. CONCLUSIONS: Increase in heart rate may unmask late potentials in patients prone to malignant ventricular arrhythmias. Therefore, functional late potential analysis with non-invasive clinical stress tests, i.e. exercise tests, should be performed only with an adequate rate response. This might identify patients at risk of malignant ventricular arrhythmias otherwise not identified with conventional late potential analysis.     

CRT术后QRS波时限改变对左心功能的影响

目的 观察顽固性充血性心力衰竭(CHF)患者心脏再同步化治疗(CRT)术后QRS波时限改变及其对左心功能的影响.方法 60例患者接受CRT术,心功能(NYHA分级)Ⅲ～Ⅳ级,左室射血分数(LVEF)11%～35%(27.15±6.35%),左室舒张末期内径(LVEDd)60～106mm(75.35±11.01mm),Q...     

Assessment of upgrading to biventricular pacing in patients with right ventricular pacing and congestive heart failure after atrioventricular junctional ablation for chronic atrial fibrillation.

AIMS: Effects of cardiac resynchronization therapy (CRT) in patients with right ventricular pacing and congestive heart failure (CHF) have only been reported in limited series. CRT in patients with atrial fibrillation remains controversial. Patients with AV junctional ablation offer a unique opportunity to study the effects of CRT in patients with right ventricular pacing combined with atrial fibrillation. The aims of the present study were to evaluate the effects of upgrading to biventricular pacing patients with CHF, permanent atrial fibrillation, and prior ablation of the atrioventricular (AV) junction followed by conventional right ventricular pacing. METHODS AND RESULTS: We studied 16 consecutive patients with permanent atrial fibrillation treated by AV junctional ablation. After a mean follow-up of 20+/-19 months (6 weeks to 5 years) they were successfully upgraded to biventricular pacing for severe CHF. Parameters were prospectively evaluated at baseline and at 6 months. The 14 surviving patients at 6 months demonstrated significant improvement (P<0.02) in New York Heart Association class but the exercise test parameters remained unchanged. Cardiothoracic ratio decreased by 5% (P=0.04), end-systolic diameter by 8% (P=0.001), end-diastolic diameter by 4% (P=0.08), systolic pulmonary artery pressure by 17% (P<0.0001) and mitral regurgitation area by 40% (P<0.05). Ejection fraction increased by 17% (P=0.11) and fractional shortening by 24% (P=0.01). CONCLUSION: CRT improves left ventricular performance and functional status in patients with permanent atrial fibrillation and prior remote right ventricular pacing.     

Exercise is superior to pacing for T wave alternans measurement in subjects with chronic coronary artery disease and left ventricular dysfunction

INTRODUCTION: T wave alternans (TWA) is a heart rate-dependent marker of vulnerability to ventricular arrhythmias. Atrial pacing and exercise both are used as provocative stimuli to elicit TWA. However, the prognostic value of the two testing methods has not been compared. The aim of this prospective study was to compare the prognostic value of TWA measured during bicycle exercise and atrial pacing in a large cohort of high-risk patients with ischemic heart disease and left ventricular dysfunction. METHODS AND RESULTS: This was a prospective study of 251 patients with coronary artery disease and left ventricular dysfunction who were referred for electrophysiologic studies (EPS) for standard clinical indications. Patients underwent TWA testing using bicycle ergometry (exercise TWA, n = 144) and/or atrial pacing (pacing TWA, n = 178). The primary endpoint was the combined incidence of death, sustained ventricular arrhythmias, and appropriate implantable cardioverter defibrillator therapy. The predictive value of exercise and pacing TWA for EPS results and for endpoint events was determined. Exercise and pacing TWA both were significant predictors of EPS results (odds ratios 3.0 and 2.9 respectively, P < 0.02). Kaplan-Meier survival analysis of the primary endpoint revealed that exercise TWA was a significant predictor of events (hazard ratio 2.2, P = 0.03). In contrast, pacing TWA had no prognostic value for endpoint events (hazard ratio 1.1, P = 0.8). CONCLUSION: TWA should be measured during exercise when it is used for clinical risk stratification. EPS results may not be an adequate surrogate for spontaneous events when evaluating new risk stratification tests.     

Beneficial effect of amiodarone on cardiac mortality in patients with asymptomatic complex ventricular arrhythmias after acute myocardial infarction and preserved but not impaired left ventricular function.

To determine whether the beneficial effect of low-dose amiodarone on survival in patients with complex ventricular arrhythmias after myocardial infarction was dependent on left ventricular (LV) function, results of the Basel Antiarrhythmic Study of Infarct Survival were analyzed. Two hundred twelve patients after acute myocardial infarction with asymptomatic complex arrhythmias were randomly assigned to receive amiodarone 200 mg/day or to a control group and followed up for 1 year. Results of mortality and arrhythmic events were related to baseline radionuclide LV ejection fraction. With preserved (greater than or equal to 40%) LV ejection fraction, there was a significantly lower 1-year cardiac mortality in patients treated with amiodarone (1 of 68 or 1.5%) versus control subjects (5 of 56 or 8.9%; p less than 0.03). This was not the case for patients with LV ejection fraction less than 40%. Similarly, arrhythmic events were significantly reduced only in patients with preserved LV function. These results suggest an interaction between the effects of amiodarone on survival and LV dysfunction in patients after acute myocardial infarction. Because of 2 other small studies with similar results, this finding may be of clinical relevance and should be addressed in ongoing and future research with this drug.     

Abnormal left ventricular wall movement in patients with chest pain and normal coronary arteriograms. Relation to inferior T wave changes and mitral prolapse.

Left ventriculograms of 45 patients with angina and normal coronary arteriograms were digitised frame by frame in order to detect regional abnormalities of wall movement. Though left ventricular pressures, end-diastolic volume, and ejection fraction were normal in all, regional outward movement during early systole was present in 10 patients, and abnormal inward wall movement during isovolumic relaxation also in 10, involving the apex or inferior surface. Both were present together in 8 patients, and affected segments showed normal amplitude and peak velocity of movement during ejection. These disturbances of wall movement were associated with inferior T wave changes on the electrocardiogram, and mitral prolapse, particularly when the latter resulted from delayed movement of the valve during ejection. It is suggested that the onset of contraction is delayed in affected areas, but that it proceeds normally thereafter. The resulting persistence of tension into the period of relaxation of the remainder of the ventricle may interfere locally with coronary flow, particularly during tachycardia, thus causing manifestations of regional ischaemia.     

Abnormal left ventricular wall movement in patients with chest pain and normal coronary arteriograms. Relation to inferior T wave changes and mitral prolapse.

Left ventriculograms of 45 patients with angina and normal coronary arteriograms were digitised frame by frame in order to detect regional abnormalities of wall movement. Though left ventricular pressures, end-diastolic volume, and ejection fraction were normal in all, regional outward movement during early systole was present in 10 patients, and abnormal inward wall movement during isovolumic relaxation also in 10, involving the apex or inferior surface. Both were present together in 8 patients, and affected segments showed normal amplitude and peak velocity of movement during ejection. These disturbances of wall movement were associated with inferior T wave changes on the electrocardiogram, and mitral prolapse, particularly when the latter resulted from delayed movement of the valve during ejection. It is suggested that the onset of contraction is delayed in affected areas, but that it proceeds normally thereafter. The resulting persistence of tension into the period of relaxation of the remainder of the ventricle may interfere locally with coronary flow, particularly during tachycardia, thus causing manifestations of regional ischaemia.     

Inappropriate pacing inhibition triggered by QT prolongation due to T wave oversensing in an ICD recipient presenting with long QT syndrome

Inappropriate inhibition of atrial pacing due to T-wave oversensing (TWOS) was observed in a patient presenting with congenital long QT syndrome, treated with an implantable cardioverter defibrillator (ICD) and beta-adrenergic blocker. Development of TWOS was associated with further QT interval prolongation in the absence of amplitude changes in the intracardiac T and R waves. Replacement of the ICD generator with a sensing filter designed to attenuate the intracardiac T wave suppressed TWOS and normalized the pacing functions.     

Deleterious effect of unintentional pacing from the middle cardiac vein in a patient with congenitally corrected transposition of the great arteries and ventricular septal defect. The beneficial effect of cardiac resynchronization therapy after heart surgery

This report presents a case of a 31-year-old male with congenitally corrected transposition of the great arteries, ventricular septal defect (VSD) and complete heart block who was admitted to our institution because of an exacerbation of heart failure after pacemaker implantation. The ECG and chest radiograph revealed that the ventricular lead was placed in the middle cardiac vein. After cardiosurgical procedure (VSD closure and atrioventricular valves replacement), the clinical symptoms of heart failure were still present. They diminished while the patient was on escape rhythm (40–70 bpm). Therefore, the previously implanted leads were removed and the transvenous, biventricular system was implanted, which resulted in a significant clinical improvement.     

Diagnosis of cardiac tamponade by echocardiography: changes in mitral valve motion and ventricular dimensions, with special reference to paradoxical pulse.

The echocardiographic findings in three patients who presented with pericardial effusion and cardiac tamponade are described. Cyclic respiratory changes affected the diastolic movement of the anterior mitral leaflet, viz., during inspiration its anterior excursion decreased in amplitude and the E-F slope diminished. This inspiratory alteration in mitral valve motion was accompanied by an increase in right ventricular dimensions and a reciprocal decrease in left ventricular dimensions. Pericardial paracentesis confirmed the presence of effusion and relieved cardiac tamponade in all the patients. Repeat echocardiography, performed in two of the patients immediately after the pericardial tap, showed that the E-F slope had become steeper and that phasic respiratory variations in the diastolic motion of the anterior mitral leaflet were no longer present. The compatibility of our observations with the theories which endeavor to explain the mechanism of the paradoxical pulse in pericardial effusion with cardiac tamponade is discussed. We suggest that the abnormalities in anterior mitral leaflet motion defined by echocardiography constitute a useful addition to the study of patients with suspected cardiac tamponade resulting from pericardial effusion.     

IL-2 and IFN-gamma, but not IL-4 secretion by peripheral blood mononuclear cells (PBMC) are related to CD4+ T cells and clinical status in Brazilian HIV-1-infected subjects.

It has been reported that production of IL-2 and IFN-gamma, known as T-helper type 1 cytokines, by peripheral mononuclear cells (PBMC) decreases with progression of HIV infection. In contrast, IL-4 and IL-10 production, Th2 cytokine profile, increases with HIV disease progression. PBMC were evaluated from 55 HIV-infected subjects from Divis?o de Imunologia, Hospital das Clínicas, Faculdade de Medicina da Universidade de S?o Paulo, to "in vitro" cytokines production after 24 hours of stimulation with PHA. Low levels of IL-4 production in both HIV-infected patients and normal subjects, were detected. The patients with CD4+ T cell counts < 200 showed a significant decrease of IL-2 and IFN-gamma production compared to controls. Patients with higher counts of CD4+ T cells (either between 200-500 or > 500 cells/mm3) also showed decreased production of IL-2 that was not statistically significant. There was a correlation between IL-2 and IFN-gamma release with CD4+ T cells counts. HIV-1-infected individuals with CD4+ T cells > 500 cells/mm3 showed increased levels of IL-2 and IFN-gamma, than individuals with CD4+ T cells < 500 cells/mm3. In conclusion, we observed a decline of IL-2 and IFN-gamma production at advanced HIV disease. IL-4 production was not affected during HIV infection. Taken together, these findings suggest that the cytokine profile might be influenced by the HIV infection rather than the cause of disease progression.     

Desensitization of cardiac beta-adrenoceptor signaling with heart failure produced by myocardial infarction in the rat. Evidence for the role of Gi but not Gs or phosphorylating proteins.

This study examined mechanisms of beta-adrenergic (AR) desensitization in a myocardial infarction (MI) model of heart failure in the rat. Inotropic responses to isoproterenol (non-selective beta-AR agonist) and RO 363 (selective beta1-AR agonist), in left atria and left papillary muscle, were reduced by up to 65%, while chronotropic responses in right atria were unaffected. beta1- and beta2-AR density did not change after MI, suggesting that changes in beta-AR responsiveness are due to changes occurring downstream of the receptor. Inotropic and chronotropic responses to forskolin were not altered in right and left atria and left papillary muscle after MI, suggesting changes at the level of the G-proteins. Pertussis toxin treatment of animals restored inotropic responses to isoproterenol in left atria and left papillary muscle to levels seen in the sham group, indicating that inactivation of Gi-proteins improves inotropic function in MI rats, and that beta-ARs couple to Gi in cardiac failure. Expression of G-protein receptor kinase 2 (GRK2), beta-arrestin1 and the regulatory subunits of cAMPdPK (RI alpha and RII alpha), showed no change after MI. However the expression of Gi alpha2 was significantly increased in left ventricle (sham 0.888+/-0.140, MI 1. 759+/-0.352 P=0.026), right ventricle (sham 0.031+/-0.004, MI 0. 037+/-0.002 P=0.006) and atria (sham 0.107+/-0.006, MI 0.138+/-0.006 P=0.004), with no changes observed in the expression of Gs alpha. These results suggest that increases in Gi play an important role in the decreased beta-AR responsiveness in the rat model of MI.     

The p22 phox A640G gene polymorphism but not the C242T gene variation is associated with coronary heart disease in younger individuals.

BACKGROUND: Most recently, evidence has been presented that the NADH/NADPH oxidase p22 phox C242T, but not the A640G gene polymorphism is associated with a reduced risk of coronary artery disease (CAD). METHODS AND RESULTS: We analysed the relationships of both p22 phox gene polymorphisms to CAD in 2205 male Caucasians whose coronary anatomy was defined by means of coronary angiography. In the total population and in high and low risk groups the relative frequencies of the C242T alleles were essentially the same in patients without or with CAD and in individuals without or with myocardial infarction. In contrast, the G allele of the A640G polymorphism was significantly more frequent in subjects without CAD than in patients with CAD (Odds ratio (OR) 0.74 (0.57-0.98); P = 0.038 in multiple logistic regression (MLR)). Correspondingly, the AA genotype of A640G was preferentially found in patients with CAD. These associations did not disappear when the analyses were corrected for multiple comparisons for other gene polymorphisms (ACE I/D gene variation, angiotensinogen T174M and M235T gene polymorphisms, AT1 receptor gene variation, phox C242T gene polymorphism, paraoxonase PON54 and PON191 gene variations) (2p = 0.01 in MLR for the presence of CAD; 2p = 0.039 in multiple regression for the extent of CAD). The association of the A640G gene variation with the presence and extent of CAD was not only identified in the total sample, but was even stronger in various high risk subpopulations of younger individuals (e.g. with hypertension with or without increased apolipoprotein B plasma levels). CONCLUSIONS: Our observations allow the assumption that the p22 phox A640G gene polymorphism is independently associated with the presence and extent of coronary artery disease.