Activation of electrical triggers of atrial fibrillation in hyperthyroidism.

CONTEXT: A shortening of the atrial refractory period has been considered as the main mechanism for the increased risk of atrial fibrillation in hyperthyroidism. However, other important factors may be involved. OBJECTIVE: Our objective was to determine the activity of abnormal supraventricular electrical depolarizations in response to elevated thyroid hormones in patients without structural heart disease. PATIENTS AND DESIGN: Twenty-eight patients (25 females, three males, mean age 43+/-11 yr) with newly diagnosed and untreated hyperthyroidism were enrolled in a prospective trial after exclusion of heart disease. Patients were followed up for 16 +/- 6 months and studied at baseline and 6 months after normalization of serum TSH levels. MAIN OUTCOME MEASURES: The incidence of abnormal premature supraventricular depolarizations (SVPD) and the number of episodes of supraventricular tachycardia was defined as primary outcome measurements before the start of the study. In addition, heart rate oscillations (turbulence) after premature depolarizations and heart rate variability were compared at baseline and follow-up. RESULTS: SVPDs decreased from 59 +/- 29 to 21 +/- 8 per 24 h (P = 0.003), very early SVPDs (so called P on T) decreased from 36 +/- 24 to 3 +/- 1 per 24 h (P < 0.0001), respectively, and nonsustained supraventricular tachycardias decreased from 22 +/- 11 to 0.5 +/- 0.2 per 24 h (P = 0.01) after normalization of serum thyrotropin levels. The hyperthyroid phase was characterized by an increased heart rate (93 +/- 14 vs. 79 +/- 8 beats/min, P < 0.0001) and a decreased turbulence slope (3.6 vs. 9.2, P = 0.003), consistent with decreased vagal tone. This was confirmed by a significant decrease of heart rate variability. CONCLUSION: Hyperthyroidism is associated with an increased supraventricular ectopic activity in patients with normal hearts. The activation of these arrhythmogenic foci by elevated thyroid hormones may be an important causal link between hyperthyroidism and atrial fibrillation.

Frequency distribution of collateral flow and factors influencing collateral channel development. Functional collateral channel measurement in 450 patients with coronary artery disease.

OBJECTIVES: We sought to determine the pathogenetic predictors of collateral channels in a large cohort of patients with coronary artery disease (CAD). BACKGROUND: The frequency distribution of collateral flow in patients with CAD is unknown. Only small qualitative studies have investigated which factors influence the development of collateral channels. METHODS: In 450 patients with one- to three-vessel CAD undergoing percutaneous transluminal coronary angioplasty (PTCA), collateral flow was measured. A collateral flow index (CFI; no unit) expressing collateral flow relative to normal anterograde flow was determined using coronary wedge pressure or Doppler measurements through sensor-tipped PTCA guide wires. Frequency distribution analysis of CFI and univariate and multivariate analyses of 32 factors, including gender, age, patient history, cardiovascular risk factors, medication and coronary angiographic data, were performed. RESULTS: Two-thirds of the patients had a CFI < 0.25 and approximately 40% of patients had a CFI < 0.15, but only approximately 10% of the patients had a recruitable CFI > or =0.4. By univariate analysis, the following were predictors of CFI > or =0.25: high levels of high-density lipoprotein cholesterol, the absence of previous non-Q-wave myocardial infarction, angina pectoris during an exercise test, angiographic indicators of severe CAD and the left circumflex or right coronary artery as the collateral-receiving vessel. Percent diameter stenosis of the lesion undergoing PTCA was the only independent predictor of a high CFI. CONCLUSIONS: This large clinical study of patients with CAD in whom collateral flow was quantitatively assessed reveals that two-thirds of the patients do not have enough collateral flow to prevent myocardial ischemia during coronary occlusion, and that coronary lesion severity is the only independent pathogenetic variable related to collateral flow.

Promotion of collateral growth by granulocyte-macrophage colony-stimulating factor in patients with coronary artery disease: a randomized, double-blind, placebo-controlled study.

BACKGROUND: Experimentally, activated macrophages have been documented to induce vascular proliferation. METHODS AND RESULTS: In 21 patients (age 74+/-9 years) with extensive coronary artery disease not eligible for coronary artery bypass surgery, the effect of granulocyte-macrophage colony-stimulating factor (GM-CSF, Molgramostim) on quantitatively assessed collateral flow was tested in a randomized, double-blind, placebo-controlled fashion. The study protocol consisted of an invasive collateral flow index (CFI) measurement immediately before intracoronary injection of 40 microg of GM-CSF (n=10) or placebo (n=11) and after a 2-week period with subcutaneous GM-CSF (10 microg/kg) or placebo, respectively. CFI was determined by simultaneous measurement of mean aortic pressure (P(ao), mm Hg), distal coronary occlusive pressure (P(occl), mm Hg; using intracoronary sensor guidewires), and central venous pressure (CVP, mm Hg): CFI=(P(occl)-CVP)/(P(ao)-CVP). CFI, expressing collateral flow during coronary occlusion relative to normal antegrade flow during vessel patency, changed from 0.21+/-0.14 to 0.31+/-0.23 in the GM-CSF group (P<0.05) and from 0.30+/-0.16 to 0.23+/-0.11 in the placebo group (P=NS). The treatment-induced difference in CFI was +0.11+/-0.12 in the GM-CSF group and -0.07+/-0.12 in the placebo group (P=0.01). ECG signs of myocardial ischemia during coronary balloon occlusion occurred in 9 of 10 patients before and 5 of 10 patients after GM-CSF treatment (P=0.04), whereas they were observed in 5 of 11 patients before and 8 of 11 patients after placebo (P=NS). CONCLUSIONS: This first clinical study investigating the potential of GM-CSF to improve collateral flow in patients with coronary artery disease documents its efficacy in a short-term administration protocol.

Accurate determination of mitral regurgitation by assessing its influence on the combined diastolic mitral and pulmonary venous flow: just 'looking twice'.

AIMS: To assess the diagnostic accuracy of combined transmitral E wave velocity and reversed systolic pulmonary venous flow for the quantification of mitral regurgitation severity. METHODS AND RESULTS: Measuring forward and total left ventricular stroke volume, mitral regurgitation severity was assessed quantitatively by calculating the regurgitant fraction in 106 consecutive patients with pure mitral regurgitation. According to the regurgitant fraction, the optimal E wave velocity for accurate distinction of mild to moderate and more than moderate mitral regurgitation was chosen by calculating the receiver-operating characteristic plot. Severe mitral regurgitation was defined by reversed systolic pulmonary venous flow. Combining transmitral E wave velocity and reversed systolic pulmonary venous flow had an overall accuracy of 78% (95% CI 70--86%) for classification of mitral regurgitation severity. E wave velocity >1.0ms(-1) predicted more than moderate mitral regurgitation with 78% sensitivity (95% CI 69-86%) and 90% specificity (95% CI 82--95%), resulting in a positive likelihood ratio of 8.1 (95% CI 5--15) and negative likelihood ratio of 0.25 (95% CI 0.18--0.35). For reversed systolic pulmonary venous flow in the presence of increased E wave velocity, the sensitivity and specificity to detect severe mitral regurgitation was 78% (95% CI 69--86%) and 97% (95% CI 92--99%) with the corresponding positive and negative likelihood ratio of 29 (95% CI 11--96) and 0.22 (95% CI 0.14--0.31). Test accuracy was independent of systolic function in a multivariate regression analysis. CONCLUSIONS: 'Looking twice', once at the transmitral E wave velocity and once at pulmonary venous flow in patients with mitral regurgitation, allows accurate determination of moderately severe and severe mitral regurgitation.