Arrhythmic disorder mapped to chromosome 1q42-q43 causes malignant polymorphic ventricular tachycardia in structurally normal hearts.
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OBJECTIVES: The purpose of this study was to provide clinical and anatomical characteristics as well as genetic background of a malignant arrhythmogenic disorder. BACKGROUND: An inherited autosomally dominant cardiac syndrome causing stress-induced polymorphic ventricular tachycardia and syncope in the absence of structural myocardial changes was detected in two families. METHODS: Two unrelated families with six victims of sudden death and 51 living members were evaluated. Resting and exercise electrocardiograms (ECG), echocardiography, magnetic resonance imaging (MRI), cineangiography, microscopic examination of endomyocardial biopsies and a drug testing with a class IC antiarrhythmic agent flecainide were performed. A genetic linkage analysis was carried out to map the gene locus. RESULTS: Of the 24 affected individuals, 10 had succumbed with six cases of sudden death, and 14 survivors showed evidence of disease. Exercise stress test induced ventricular bigeminy or polymorphic ventricular tachycardia in affected individuals. Three children initially examined before 10 years of age developed arrhythmias during a four-year follow-up. Resting ECGs were normal in affected subjects except a slight prolongation of the QT intervals adjusted for heart rate (QTc) (430 +/- 18 vs. 409 +/- 19 ms, affected vs. nonaffected, p < 0.01). Administration of flecainide did not induce ECG abnormalities encountered in familial idiopathic ventricular fibrillation. Ventricular volumes, contractility and wall measurements were normal by echocardiography, right ventricular cineangiography and MRI. Histopathological examination showed no fibrosis or fatty infiltration. The cumulative cardiac mortality by the age of 30 years was 31%. The disease locus was assigned to chromosome 1q42-q43, with a maximal pairwise lod score of 4.74 in the two families combined. Only one heterozygous carrier was clinically unaffected suggesting high disease penetrance in adulthood. CONCLUSIONS: A distinct cardiac disorder linked to chromosome 1q42-q43 causes exercise-induced polymorphic ventricular tachycardia in structurally normal hearts and is highly malignant. Delayed clinical manifestation necessitates repeated exercise electrocardiography to assure diagnosis in young individuals of the families. (+info)
Effects of bradykinin on coronary blood flow and vasomotion in transplant patients.
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OBJECTIVES: To evaluate the effects of exogenous bradykinin on coronary epicardial and microcirculatory tone in transplant patients (HTXs), and to compare them with the effects of acetylcholine. BACKGROUND: Coronary endothelial dysfunction has been reported to occur early after heart transplantation, most notably when acetylcholine was the endothelium-function marker used. The effects of bradykinin on coronary vasomotion are unknown in HTXs. METHODS: Sixteen HTXs were compared 3.6 +/- 1.7 months after transplantation to seven control subjects. Coronary flow velocity was measured using guide-wire Doppler. Diameters (D) of three segments of the left coronary artery and coronary blood flow (CBF) were assessed at baseline, after 3-min infusions of increasing bradykinin doses (50, 150 and 250 ng/min) then of increasing acetylcholine doses (estimated blood concentrations of 10(-8), 10(-7) and 10(-6) M). RESULTS: Bradykinin induced similar dose-dependent increases in D and CBF in both groups: D was 11 +/- 12%, 19 +/- 14% and 22 +/- 16% (all p < 0.0001), and CBF was 50 +/- 40%, 130 +/- 68% and 186 +/- 77% (all p < 0.0001). Acetylcholine induced significant epicardial vasodilation in control subjects and vasoconstriction in HTX, as well as a marked increase in CBF in both groups. Acute allograft rejection, present in 8 of the 16 HTXs, did not modify responses to bradykinin, but was associated with a smaller CBF increase in response to acetylcholine (p < 0.05). CONCLUSIONS: The coronary vasodilating effects of bradykinin are preserved early after heart transplantation, even in the presence of acute allograft rejection. Although there is an abnormal vasoconstricting response to acetylcholine reflecting endothelium dysfunction, the endothelium remains a functionally active organ in heart transplant recipients. (+info)
Left ventricular angiography on exercise. A new method of assessing left ventricular function in ischaemic heart disease.
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Left ventricular function was studied in 17 patients with ischaemic heart disease and compared with 4 patients with normal left ventricular function. The patients in the homogeneous group of ischaemic heart disease were further subdivided into those 'without angina' (n=5) and those 'with angina' (n=12), depending upon the presence of angina during supine leg exercise at the time of definitive study. At rest there was no significant difference in the heart rate, cardiac output, stroke volume, and left ventricular end-diastolic pressure (LVEDP) in the three groups. During exercise the cardiac output and stroke volume were significantly depressed and LVEDP was significantly raised in the ischaemic heart disease group as a whole but within this group failed to show any significant difference in patients with and without angina. The left ventricular end-diastolic volume (LVEDV) and end-systolic volume (LVESV) measurements showed clear separation of these three groups only on exercise. On exercise, there was decrease in LVEDV and LVESV (P less than 0.05; P less than 0.02) in the group with normal left ventricular function, no change in the group with ischaemic heart disease without angina, and striking increase in LVEDV and LVESV in the group with ischaemic heart disease and angina (P less than 0.01 and P less than 0.02, respectively). This angiographic method of assessing left ventricular function shows clear separation of the three groups and also highlights the significance of angina. Ejection fraction (EF), a commonly measured parameter of left ventricular function, failed to reflect consistent changes on exercise as compared to values at rest which emphasizes the limitations of the measurement of ejection fraction at rest. (+info)
Significance of angina pectoris in aortic valve stenosis.
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Of 60 patients aged 45 to 66 years with aortic valve stenosis, 28 (47 per cent) had angina pectoris. Significant coronary arterial obstruction was shown by selective coronary cineangiography in 14 of them. Systolic pressure gradients across the aortic valve were lower in patients with angina than in those without. In those with angina, systolic gradients were higher in those with normal coronary arteriograms than in those with demonstrable coronary arterial disease. Aortic valve replacement relieved the angina in all patients who had normal coronary arteriograms. When valve replacement was combined with coronary bypass grafting in those with coronary arterial disease, surgical mortality was higher and symptomatic relief less predictable. Incapacitating angina in patients with aortic stenosis was nearly always associated with significant coronary disease. In those with less severe angina it was impossible to predict the state of the coronary arteries. Two patients, who did not have angina and who did not undergo coronary arteriography, died after aortic valve replacement and were found at necropsy to have unsuspected severe coronary disease. We, therefore, suggest that coronary arteriography should be carried out in all patients over the age of 40 years in whom surgery is being considered for aortic stenosis. (+info)
Videometric analysis of regional left ventricular function before and after aortocoronary artery bypass surgery: correlation of peak rate of myocardial wall thickening with late postoperative graft flows.
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The peak rate of systolic wall thickening (pdTw/dt) in regions of the left ventricle was determined by biplane roentgen videometry in 60 patients before and a median of 14 mo after aorto-coronary bypass graft surgery. The left ventricular ejection fraction, stroke volume, and end-diastolic volume and pressure did not change significantly after surgery in the presence of patent or occluded grafts (P greater than 0.05). Statistically significant increases occurred in the peak rate of systolic wall thickening regions supplied by patent bypass grafts, and significant decreases occurred in regions with occluded grafts (P less than 0.01). Of 42 preoperatively hypokinetic regions (pdTw/dt greater than 0 less than 5.0 cm/s) supplied by a patent graft, 30 improved by an average of 2.6 cm/s after operation; 18 returned to normal. Failure of 24 hypokinetic regions to improve to normal was associated with myocardial infarction in 11 or with late postoperative graft blood flows of less than 60 ml/min measured by videodensitometry, in 10. All seven preoperatively akinetic (pdTw/dt=0) or dyskinetic (pdTw/dt less than 0) regions did not improve after the operation despite the fact that, in five of the seven, coronary bypass flows were over 60 ml/min. All eight preoperatively hypokinetic regions supplied by coronary artery graft flows of less than or equal 40 ml/min failed to improve to normal after operation. All nine preoperatively hypokinetic regions supplied by coronary artery graft flows of over 60 ml/min improved to normal after surgery. Late postoperative coronary artery bypass graft flows, the functional status of the myocardium, the status and distribution of the native coronary circulation, and decreased regional function elsewhere in the ventricle must all be considered when regional left ventricular function is interpreted. (+info)
Early alteration of coronary hemodynamics in late restenosis after coronary angioplasty.
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It is not known whether changes in coronary hemodynamics may antedate the development of restenosis after percutaneous coronary transluminal angioplasty (PTCA). The purpose of this study was to evaluate the early change in coronary microvascular function in patients with late restenosis after PTCA. Coronary hemodynamics were studied in series before, immediately after, 2 weeks and 3 months after successful PTCA in 12 male patients with a single lesion of the left anterior descending coronary artery. In each patient, great cardiac venous flow (GCVF) and oxygen content were measured both at baseline and during hyperemia induced by adenosine infusion. The sequential changes of coronary hemodynamics were compared between patients with and without restenosis at 3 months after PTCA. Basic characteristics did not differ between the patients with (n = 6) and those without restenosis (n = 6). Luminal diameter stenosis (in percentage) was also similar between the two groups both before (79.2 +/- 18.4% vs 83.0 +/- 9.6%, p = NS) and up to 2 weeks after PTCA (25.8 +/- 10.9% vs 28.5 +/- 7.9%, p = NS). In patients without restenosis, basal and hyperemic GCVF was unchanged up to 2 weeks after PTCA. There was a significant increase in CFR 3 months after PTCA. In patients with restenosis, basal GCVF was significantly increased and hyperemic GCVF was unchanged immediately after PTCA. However, 2 weeks after PTCA, basal GCVF was decreased while luminal diameter was still preserved. In comparison with those without restenosis, patients with restenosis had significantly lower CFR before (1.98 +/- 0.42 vs 2.69 +/- 0.46, p = 0.019), immediately after (1.47 +/- 0.27 vs 2.24 +/- 0.47, p = 0.006) and 3 months after PTCA (1.51 +/- 0.32 vs 3.40 +/- 0.54, p = 0.001). In patients without restenosis, the recovery of coronary microvascular function was delayed up to 3 months after PTCA. In patients with late restenosis, basal coronary microvascular tone was altered within 2 weeks after PTCA suggesting early deterioration of coronary microvascular function before the development of angiographic restenosis. (+info)
Evaluation of portable radionuclide method for measurement of left ventricular ejection fraction and cardiac output.
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Seventeen patients with coronary artery, valvular, or myopathic heart disease were studied to determine correlations of the cardiac output and ejection fraction when comparing the results obtained with a portable probe technique using 113mIn with those obtained with standard methods (cineangiographic, Fick, and dye dilution). With ejection fractions ranging from o.10 to 0.85, the coefficient of correlation was 0.90 when comparing cineangiographic and radionuclide techniques. Cardiac output determinations by the radionuclide technique also correlated well with standard methods (r equals 0.88). The radionuclide method shows promise as an accurate, safe, and simple method in the evaluation of cardiac function at the bedside. (+info)
Spontaneous reversal of portal blood flow: the case for and against its occurrence in patients with cirrhosis of the liver.
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Because of its presumed serious clinical significance, we made an analysis of the evidence for and against the occurrence of spontaneous reversal of portal flow in cirrhosis of the liver. We examined the evidence obtained from manometric studies, radioactive tracer studies, radiologic studies, and actual measurements of magnitude and direction of portal blood flow. Concerning manometric studies, we introduced a physical analysis, based on first principles, which demonstrates that the occluded portal pressures cannot be used to construct a hydraulic gradient for portal flow. Similarly, we examined the weakness of the evidence derived from radioactive tracer and radiologic studies and, in the latter, the drastically opposite results reported by different investigators. Finally, we found that actual measurements of magnitude and direction of portal flow provide impressive evidence against the occurrence of spontaneous reversal of portal flow in cirrhosis. We conclude that unless new and convincing evidence is provided, it may not serve the best interests of medicine and of our patients to continue accepting spontaneous reversal of portal flow in cirrhosis as if it were a proven phenomenon. (+info)