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Biomedical subjects

Arthur J Moss

Publications and source records attributed to Arthur J Moss.

At least 91 records · Page 5Linked to original sources

Exercise testing.

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Cardiology↗

Risk stratification using heart rate turbulence and ventricular arrhythmia in MADIT II: usefulness and limitations of a 10-minute holter recording.

BACKGROUND: We evaluated the usefulness of heart rate turbulence (HRT) parameters and frequency of ventricular premature beats (VPBs) for risk-stratifying postinfarction patients with depressed left ventricular function enrolled in Multicenter Automatic Defibrillator Trial II (MADIT II). METHODS: In 884 MADIT II patients, 10-minute Holter monitoring at enrollment was used to evaluate HRT parameters and frequency of VPBs. The primary endpoints were defined as all-cause mortality in patients randomized to conventional treatment and as appropriate therapy for ventricular tachycardia or fibrillation in patients randomized to implantable cardioverter defibrillator (ICD) therapy. RESULTS: The median turbulence slope was lower in patients who died in comparison to survivors in the conventional arm (2.3 vs 4.5 ms/RR; P < 0.05); but it was not a significant predictor of mortality after adjustment for clinical covariates (age, ejection fraction, beta-blocker use, and BUN levels). There was no association between HRT parameters and arrhythmic events in ICD patients. Conventionally treated patients who died and ICD patients who had appropriate ICD therapy had significantly more frequent VPBs than those without such adverse events. After adjustment for clinical covariates, frequent VPBs>3/10 min were associated with death in the conventional arm (HR = 1.63; P = 0.070) and were predictive for appropriate ICD therapy in the ICD arm (HR = 1.75; P = 0.003). CONCLUSION: In postinfarction patients with severe left ventricular dysfunction, frequent VPBs are associated with increased risk of mortality and with appropriate ICD therapy. HRT obtained from 10-min Holter ECG showed a trend toward the association with mortality in univariate analysis but HRT parameters were not predictive of the outcome in multivariate analyses.

Adult↗

Modulating effects of age and gender on the clinical course of long QT syndrome by genotype.

OBJECTIVES: We aimed to determine whether long QT syndrome (LQTS) genotype has a differential effect on clinical course of disease in male and female children and adults after adjustment for QTc duration. BACKGROUND: Genotype influences clinical course of the LQTS; however, data on the effect of age and gender on this association are limited. METHODS: The LQTS genotype, QTc duration, and follow-up were determined in 243 cases of LQTS caused by the KCNQ1 potassium channel gene mutations (LQT1), 209 cases of LQTS caused by the HERG potassium channel gene mutations (LQT2), and 81 cases of LQTS caused by the SCN5A sodium channel gene mutation (LQT3) gene carriers. The probability of cardiac events (syncope, aborted cardiac arrest, or sudden death) was analyzed by genotype, gender, and age (children < or = 15 years and adults 16 to 40 years). In addition, the risk of sudden death and lethality of cardiac events were evaluated in 1,075 LQT1, 976 LQT2, and 324 LQT3 family members from families with known genotype. RESULTS: During childhood, the risk of cardiac events was significantly higher in LQT1 males than in LQT1 females (hazard ratio [HR] = 1.72), whereas there was no significant gender-related difference in the risk of cardiac events among LQT2 and LQT3 carriers. During adulthood, LQT2 females (HR = 3.71) and LQT1 females (HR = 3.35) had a significantly higher risk of cardiac events than respective males. The lethality of cardiac events was highest in LQT3 males and females (19% and 18%), and higher in LQT1 and LQT2 males (5% and 6%) than in LQT1 and LQT2 females (2% for both). CONCLUSIONS; Age and gender have different, genotype-specific modulating effects on the probability of cardiac events and electrocardiographic presentation in LQT1 and LQT2 patients.

Adolescent↗

History of hypertension and enhanced thrombogenic activity in postinfarction patients.

Hypertension is a risk factor for coronary thrombosis and death in cardiac patients mediated in part by endothelial damage or dysfunction and increased thrombogenicity. However, there are no data regarding the association between hypertension and thrombogenic activity in stable patients after myocardial infarction and limited data about the prognostic significance of thrombogenic factors in hypertensive patients after infarction. Therefore, levels of thrombogenic, lipid, and inflammatory factors were measured 2 months after an acute myocardial infarction in 461 hypertensive and 582 nonhypertensive patients. Thrombogenic factors included d-dimer, fibrinogen, plasminogen activator inhibitor-1, von Willebrand factor, factor VII, and factor VIIa. Lipid variables included cholesterol (total, HDL, LDL), triglyceride, lipoprotein (a), apolipoprotein-A1, and apolipoprotein-B. The prognostic significance of these factors for predicting cardiac events during a 2-year follow-up was evaluated in hypertensive and nonhypertensive patients. In comparison with nonhypertensive patients, those with hypertension had higher levels of d-dimer (607 versus 453 mg/L, P<0.001), fibrinogen (3.64 versus 3.43 g/L, P<0.001), plasminogen activator inhibitor-1 (29.7 versus 27.3 ng/mL, P=0.01), von Willebrand factor (159 versus 141 IU/dL; P<0.001), and higher levels of inflammatory markers (hsCRP and SAA). In multivariate analysis after adjustment for clinical covariates, elevated d-dimer was the only factor independently associated with a history of hypertension (OR, 1.38, P=0.05). d-Dimer was associated with an increased risk of recurrent cardiac events in both hypertensive (hazard ratio=3.02, P=0.005) and nonhypertensive (hazard ratio=2.42, P=0.02) patients. Thus, patients after infarction with a history of hypertension have enhanced thrombogenic activity, which predisposes them to recurrent cardiac events.

Apolipoproteins↗

Metabolic syndrome best defines the multivariate distribution of blood variables in postinfarction patients.

The hypothesis was tested that metabolic syndrome (MS) plays a leading role in approximating the multivariate distribution of thrombogenic and metabolic blood variables in a population of postinfarction patients. The multivariate statistical technique of factor analysis was used to determine blood variable clustering 2 months after myocardial infarction. Five clusters resulted in two separate independent factors, dyslipidemia and metabolic, reflecting MS and the remaining interpreted as cholesterol-lipoprotein, vascular-inflammatory, and coagulation. All five factors accounted for 55% of total variance with MS-associated factors accounting for 20% and individual factor contributions as follows: 11.6, 8.6, 12.9, 11.9, and 9.6%, respectively. There were no interactions of metabolic variables with thrombogenic variables or CRP in any factor. Results of subgroup analysis in males and females and in patients on and not on statins were all similar to the total group. We conclude there is no interaction of variables of MS or cholesterol-lipoprotein factors with those of thrombogenic factors. This independence yields the potential for use of factors in evaluating CVD risk. Further, the importance of MS in this group of postinfarction patients is emphasized, as the largest contribution to total variance was from MS factors, meaning that these variables best approximate the original multivariate distribution.

Aged↗

Noninvasive risk stratification in postinfarction patients with severe left ventricular dysfunction and methodology of the MADIT II noninvasive electrocardiology substudy.

Sudden cardiac death occurs as a result of a complex interplay of changes in myocardial substrate, imbalance of autonomic regulation of the heart, and myocardial vulnerability. Noninvasive electrocardiology serves as a comprehensive tool for investigating factors representing mechanistic pathways leading to cardiac events. Heart rate variability, nonlinear dynamics of heart rate, and heart rate turbulence provide insight into autonomic control of the heart. Prognostic value of these parameters in postinfarction patients is well established for predicting cardiac death, but there is less evidence for their association with sudden death or arrhythmic events. Electrical manifestation of changes in myocardial substrate include QRS and QTc prolongation, presence of conduction disturbances, presence of late potentials, abnormalities of repolarization morphology, and presence of nonsinus rhythm, namely atrial fibrillation. Electrocardiogram (ECG) measures reflecting myocardial vulnerability to arrhythmias include frequent ventricular premature beats, T wave alternans, or QT variability. Prognostic significance of these parameters is documented in studies focused mostly on them as individual markers of risk. The noninvasive electrocardiology substudy of the Multicenter Automatic Defibrillator Implantation Trial II (MADIT II) allows for simultaneous analysis of several of the above ECG markers of risk and will provide insight about relative contribution of mechanistic pathways leading to cardiac death in postinfarction patients with severe left ventricular dysfunction. Combination of a standard 12-lead ECG and 10-minute high-resolution Holter recordings serves to evaluate the prognostic significance of noninvasive electrocardiology parameters for mortality in patients randomized to conventional treatment and for arrhythmic events in patients randomized to implantable cardioverter defibrillator therapy.

Atrial Fibrillation↗

Identification of sotalol-induced changes in repolarization with T wave area-based repolarization duration parameters.

In this study, we investigated the validity of T wave area-based parameters for the identification of drug-induced changes of repolarization. Based on electrocardiograms from 39 healthy patients, we computed the stability of repolarization measurements and compared the sotalol-induced repolarization changes when measured with area-based parameters and traditional QT interval techniques (manual and automatic). Also, we evaluated the effect of different types of heart rate correction on these repolarization measurements. The results show that the stability of the automatic repolarization measurements is higher when measured using computer algorithm than using manual QT measurement. By using a population-based heart rate correction, the area-based parameters reveal significant modification of the overall shape of the T wave in its early, middle, and final part. In conclusion, morphological parameters of T wave are able to identify the changes in repolarization interval induced by sotalol. These parameters are more stable and thus more reliable than the traditional QT interval measurements.

Electrocardiography↗

MADIT-II: substudies and their implications.

In MADIT-II, prophylactic ICD therapy was effective in improving survival in patients with prior myocardial infarction and an ejection fraction <or=0.30, and a host of prespecified secondary analyses indicate that life-saving effect of ICD therapy is consistent across all studied subgroups. We have not been able to identify any traditional risk factors that will permit selection of patients who will receive a significantly better effect from the ICD within any subgroup. The ICD provides appropriate therapy for life-threatening ventricular arrhythmias on at least one occasion in over a third of the patients during the first 4 years after device implantation. Computations from the MADIT-II database indicate that 9 patients need to be treated with an ICD to save one life during a 4-year period. The findings from MADIT-II have implications for patients, physicians, and society.

Arrhythmias, Cardiac↗

MADIT-I and MADIT-II.

The MADIT-I study was a proof-of-principle study, and this randomized trial showed that the implantable cardioverter defibrillator (ICD) saves lives in high-risk patients with coronary heart disease. The MADIT-II study showed that prophylactic ICD therapy was associated with significantly improved survival in patients with ischemic cardiomyopathy, as defined by documented coronary heart disease and advanced left ventricular dysfunction, without requiring screening for ventricular arrhythmias or inducibility by electrophysiologic testing. Taken together, these two trials, as well as the results from several other randomized ICD trials, indicate that ICD therapy is indicated in coronary patients who meet MADIT-I or MADIT-II eligibility criteria and are not excluded by major noncardiac comorbidity.

Cardiac Pacing, Artificial↗