bluuebunny/crossref_metadata_2025 huggingface dataset:
Mechanisms involved in the response to prolonged infusion of atrial natriuretic factor in patients with chronic heart failure.
Authors: Münzel T , Drexler H , Holtz J , Kurtz S , Just H
Published: June 2012

We examined the mechanisms involved in the cardiovascular and renal response to prolonged infusion of atrial natriuretic factor (ANF) in patients with chronic heart failure. ANF infusion was titrated to produce a 30% decrease in pulmonary capillary wedge pressure or a 20% increase in cardiac output, and this dose (average, 75 +/- 4 ng/kg/min) was then administered for 20 hours. The short-term response to ANF included significant reductions in central filling pressures, increases in cardiac output, modest increases in diuresis and glomerular filtration rates, significant reduction in plasma aldosterone levels, and a 3.6-fold increase in plasma cyclic GMP levels. During prolonged infusion, plasma cGMP levels and cardiac output gradually returned to baseline. Similarly, the initially increased diuretic effects were completely abolished during prolonged ANF infusion, although plasma alpha-hANF levels remained consistently elevated above baseline values (control, 198 +/- 38; titration, 2,760 +/- 596; 20 hours, 3,499 +/- 659 pg/ml). Four hours after beginning the ANF infusion, marked increases in hematocrit levels were noted (42.5 +/- 1.0% versus 45.3 +/- 1.4%, control and infusion, respectively, p less than 0.05); during this time, no change in total plasma protein concentration occurred, indicating extravascular shift of fluid and plasma proteins. No evidence was noted for activation of vasoconstrictor hormones during prolonged ANF infusion, although mean arterial pressure was significantly reduced throughout the infusion period. Plasma pro-ANF (31-67) levels, determined as a marker for endogenous ANF secretion, were significantly suppressed as were the reductions of central filling pressures. After ANF discontinuation, heart rate and pulmonary capillary wedge pressure increased significantly above baseline values without evidence for sympathetic stimulation. We conclude that 1) prolonged infusion of ANF causes only transient increases in plasma cGMP levels but a sustained reduction of the cardiac release of ANF and that 2) the beneficial hemodynamic effects of ANF, that is, unloading of the ventricles, may be associated with or, in part, may be secondary to a shift of plasma constituents into the extravascular space. The latter may limit the therapeutic potential of ANF for long-term treatment.
Single-beat estimation of the slope of the end-systolic pressure-volume relation in the human left ventricle.
Authors: Takeuchi M , Igarashi Y , Tomimoto S , Odake M , Hayashi T , Tsukamoto T , Hata K , Takaoka H , Fukuzaki H
Published: June 2012

This study assessed a new method of estimating the slope (Ees) of the end-systolic pressure-volume relation (ESPVR) from a single beat of the human heart. Left ventricular pressure was recorded with a high-fidelity micromanometer in patients with heart disease during left ventriculography. Peak isovolumic pressure at the end-disastolic volume was estimated by a curve-fitting technique from an isovolumic left ventricular pressure curve. The ESPVR line was drawn from the estimated peak isovolumic pressure-volume point tangential to the left upper corner of the pressure-volume loop. The slope of this estimated ESPVR line from single-beat analysis was compared with the slope of the ESPVR line obtained from three pressure-volume loops in 16 patients given angiotensin II or nitroglycerin infusion. The estimated Ees was 5.0 +/- 2.2 mm Hg/ml/m2, and the conventional Ees was 4.9 +/- 2.7 mm Hg/ml/m2. The estimated Ees showed a positive correlation with the conventional Ees (r = 0.91, p less than 0.001, SEE = 1.2 mm Hg/ml/m2). In the other 13 patients, after dobutamine infusion (5 micrograms/kg/min i.v.) the estimated Ees increased significantly from 5.6 +/- 1.4 to 7.4 +/- 2.0 mm Hg/ml/m2 (p less than 0.01). Thus, the estimated Ees approximated the conventional Ees and was sensitive to a positive inotropic intervention. We conclude that this single-beat analysis method facilitates assessment of the beat-by-beat ESPVR of the human heart.
Nonlinearity and load sensitivity of end-systolic pressure-volume relation of canine left ventricle in vivo.
Authors: van der Velde E T , Burkhoff D , Steendijk P , Karsdon J , Sagawa K , Baan J
Published: June 2012

The effects of mechanical changes in loading conditions on the left ventricular end-systolic pressure-volume relation (ESPVR) were studied in nine open-chest dogs, including three dogs studied before and after beta-adrenergic blockade. Left ventricular pressure was measured with a micromanometer, and left ventricular volume was measured with a conductance catheter. ESPVRs were obtained by increasing left atrial inflow over wide volume ranges (as much as threefold) under three different conditions: control or high or low aortic impedance. High impedance was obtained by occlusion of the descending aorta, and low impedance was obtained by a shunt between the subclavian artery and the left atrium. In the unblocked animals in 21 of 28 runs, a second-order polynomial equation gave a better fit for the ESPVR than a linear relation. To quantify the effects of the changes in aortic impedance on the ESPVR, we calculated from the quadratic equation its volume intercept (V18) and its local slope (E18) at an end-systolic pressure (Pes) of 18 kPa. In the unblocked animals, a statistically significant difference was found in V18 between low impedance (21.50 +/- 6.27 ml) and high impedance (14.10 +/- 8.98 ml; p less than 0.005) and between control (19.14 +/- 9.58 ml) and high impedance (p less than 0.05). In most dogs, E18 was increased at high and decreased at low impedance, but not significantly. In the additional experiments with beta-blockade, the nonlinearity diminished somewhat, but the load dependency of the ESPVR remained present after beta-blockade because the same leftward shift of the ESPVR with high aortic impedance was found. Two other relations, namely, of dP/dtmax and of stroke work versus end-diastolic volume, were also investigated, which on the whole showed the same behavior as the ESPVR. These results indicate that the ESPVR and dP/dtmax-Ved and stroke work-end-diastolic volume relations, when studied over a wide volume range, are nonlinear and that changes in loading conditions influence indexes of contractility derived from these relations, especially the volume intercepts, in such a way that an increase in aortic impedance may be interpreted as an increase in contractility. Blocking the beta-adrenergic receptors did not influence the load dependency of the ESPVR but, in some cases, tended to decrease the nonlinearity in concordance with the relation between contractility and nonlinearity in isolated hearts.
Diltiazem increases late-onset congestive heart failure in postinfarction patients with early reduction in ejection fraction. The Adverse Experience Committee; and the Multicenter Diltiazem Postinfarction Research Group.
Authors: Goldstein R E , Boccuzzi S J , Cruess D , Nattel S
Published: June 2012

The Multicenter Diltiazem Postinfarction Trial (MDPIT) reported no consistent diltiazem effect on new or worsened congestive heart failure (CHF) during 12-52 months' follow-up after acute myocardial infarction. This was puzzling in light of the observation that patients with findings suggesting left ventricular dysfunction (LVD) at baseline on diltiazem had more cardiac events (cardiac mortality or recurrent nonfatal infarction) than such patients on placebo. We hypothesized that diltiazem increased the frequency of late CHF as well as of cardiac events, but only in patients predisposed by LVD. Using the same characterizing variables as the primary MDPIT analysis, we found that patients with pulmonary congestion, anterolateral Q wave infarction, or reduced ejection fraction (EF) at baseline were more likely to have CHF during follow-up than those without these markers of LVD. CHF was particularly frequent in the patients with LVD who were randomized to diltiazem. Among those with a baseline EF of less than 0.40, late CHF appeared in 12% (39/326) receiving placebo and 21% (61/297) receiving diltiazem (p = 0.004). Life table analysis in patients with an EF of less than 0.40 confirmed more frequent late CHF in those taking diltiazem (p = 0.0017). In addition, the diltiazem-associated rise in the frequency of late CHF was progressively greater with increasingly severe decrements in baseline EF. This diltiazem effect was absent in patients with pulmonary congestion at baseline but an EF of 0.40 or more, suggesting a unique association between diltiazem-related late CHF and systolic LVD.(ABSTRACT TRUNCATED AT 250 WORDS)
Effects of colestipol-niacin therapy on human femoral atherosclerosis.
Authors: Blankenhorn D H , Azen S P , Crawford D W , Nessim S A , Sanmarco M E , Selzer R H , Shircore A M , Wickham E C
Published: June 2012

The 2-year therapy effect on femoral atherosclerosis was evaluated in the Cholesterol Lowering Atherosclerosis Study (CLAS), a randomized, placebo-plus-diet-controlled angiographic trial of colestipol-niacin therapy plus diet in men with previous coronary bypass surgery. Different diet compositions were prescribed to enhance the differential in blood cholesterol responses between the two groups. The annual rate of change in computer-estimated atherosclerosis (CEA), a measure of lumen abnormality, was evaluated between treatment groups. A significant per-segment therapy effect was found in segments with moderately severe atherosclerosis (p less than 0.04) and in proximal segments (p less than 0.02). When segmental CEA measures were combined into a per-patient score using an adaptation of the National Heart, Lung, and Blood Institute scoring procedure, a significant therapy effect was observed (p less than 0.02). Total variance of the annual change rate in CEA was as predicted from pilot studies, but measurement variation was larger. The therapy effect observed in femoral arteries, although significant, was less marked than the strong and consistent benefit previously reported for both native coronary arteries and aortocoronary bypass grafts.
Changes in left ventricular volume, mass, and function during the development and regression of supraventricular tachycardia-induced cardiomyopathy. Disparity between recovery of systolic versus diastolic function.
Authors: Tomita M , Spinale F G , Crawford F A , Zile M R
Published: June 2012

Chronic supraventricular tachycardia causes a dilated cardiomyopathy in man. Terminating this tachycardia appears to result in symptomatic improvement; however, its effects on left ventricular (LV) volume, mass, and function have not been fully examined. Accordingly, hemodynamic studies using simultaneous echocardiography and catheterization were performed in three groups of pigs: 1) those subjected to rapid left atrial pacing (240 beats/min) for 3 weeks (SVT, n = 8), 2) those subjected to supraventricular tachycardia for 3 weeks followed by termination of pacing and a 4-week recovery period (PSVT, n = 9), and 3) sham-operated controls (CTR, n = 10). Systolic pump function was assessed using fractional shortening (FS), peak ejection rate [peak (-)dD/dt], and maximum rate of pressure development [peak (+)dP/dt]. Diastolic function was assessed using the time constant of isovolumic pressure decline (tau), peak early diastolic filling rate [peak (+)dD/dt], the chamber stiffness constant (Kc), and the myocardial stiffness constant (Km). Supraventricular tachycardia caused LV dilation (end-diastolic dimension [EDD] increased from 3.5 +/- 0.4 cm in CTR to 4.9 +/- 0.5 cm in SVT, p less than 0.05) but no change in LV mass (LV weight-to-body weight ratio [LV/BW]) was 2.58 +/- 0.3 g/kg in CTR and 2.66 +/- 0.4 g/kg in SVT), all indexes of systolic function became abnormal (FS fell from 30 +/- 4% in CTR to 13 +/- 5% in SVT, p less than 0.05), and the indexes of relaxation and filling were slowed (tau increased from 36 +/- 3 msec in CTR to 51 +/- 13 msec in SVT, p less than 0.05). There were no significant changes in Kc or Km. After terminating the supraventricular tachycardia, LV volume fell but remained greater than that in CTR (EDD was 4.2 +/- 0.4 cm in PSVT, p less than 0.05 versus CTR) and substantial LV hypertrophy developed (LV/BW was 3.48 +/- 0.5 g/kg in PSVT, p less than 0.05 versus CTR). Systolic function returned to normal (FS was 31 +/- 5% in PSVT) but diastolic function remained abnormal. In PSVT, tau remained prolonged (49 +/- 12 msec, p less than 0.05 versus CTR), Kc increased from 3.7 +/- 1.0 in CTR to 7.4 +/- 1.2 (p less than 0.05), and Km increased from 4.4 +/- 1.5 in CTR to 13.9 +/- 9.7 (p less than 0.05). Thus, the improvement in systolic function that occurs after the termination of supraventricular tachycardia is associated with the development of LV hypertrophy and persistent diastolic dysfunction.
Kistrin, a polypeptide platelet GPIIb/IIIa receptor antagonist, enhances and sustains coronary arterial thrombolysis with recombinant tissue-type plasminogen activator in a canine preparation.
Authors: Yasuda T , Gold H K , Leinbach R C , Yaoita H , Fallon J T , Guerrero L , Napier M A , Bunting S , Collen D
Published: June 2012

BACKGROUND

Kistrin is a 68-amino acid polypeptide from the venom of the Malayan pit viper Agkistrodon rhodostoma, which inhibits the platelet GPIIb/IIIa receptor. Its effect on thrombolysis, reocclusion, and bleeding associated with administration of recombinant tissue-type plasminogen activator (rt-PA) was studied in a canine model of coronary artery thrombosis.

METHODS AND RESULTS

Coronary patency was monitored for 2 hours by ultrasonic flow probe and repeated coronary angiography. The rt-PA was given as 0.45-mg/kg bolus injections at 15-minute intervals until recanalization or to a maximum of four boluses. Four groups of four or five dogs were studied: a control group that received intravenous heparin (4,000-unit bolus and 1,000 units each hour) and three groups that received heparin and 0.48, 0.24, or 0.12 mg/kg kistrin, administered as a 10% bolus injection and an infusion during a 60-minute period. In the control group, reflow occurred in four of five dogs within 37 +/- 47 minutes but was followed by cyclic reflow and reocclusion. Kistrin at a dose of 0.48 and 0.24 mg/kg reduced the time to reflow to 6 +/- 5 and 10 +/- 3 minutes, respectively, and abolished reocclusion. With 0.12 mg/kg kistrin, reflow occurred in all four animals, within 27 +/- 23 minutes, and reocclusion occurred in two animals. Kistrin induced a dose-related prolongation of the template bleeding time: with 0.48 mg/kg kistrin, the bleeding time was prolonged from 3.8 +/- 1.3 minutes before infusion to 29 +/- 2 minutes during infusion, but it was shortened to 8.3 +/- 2.6 minutes at 90 minutes after the end of infusion. Kistrin also caused a dose-related inhibition of platelet aggregation with ADP and collagen: with 0.48 mg/kg kistrin, platelet aggregation was abolished during the infusion but had partially recovered toward the end of the observation period. Pathological examination of recanalized coronary arterial segments of dogs given 0.48 or 0.24 mg/kg kistrin revealed widely patent arteries with some platelets layered on the damaged intimal surface.

CONCLUSIONS

Kistrin increases the rate and extent of thrombolysis with a reduced dose of rt-PA, and it prevents reocclusion. At an effective dose, it is associated with a transient prolongation of the bleeding time and inhibition of platelet aggregation. Kistrin may offer promise as adjunctive treatment to thrombolytic agents in patients with acute myocardial infarction.
Relative efficacy of antithrombin compared with antiplatelet agents in accelerating coronary thrombolysis and preventing early reocclusion.
Authors: Haskel E J , Prager N A , Sobel B E , Abendschein D R
Published: June 2012

BACKGROUND

Optimal coronary thrombolysis should be prompt and persistent. Although activation of platelets and increased thrombin activity have been associated with clinical thrombolysis, the role of each in delaying thrombolysis or inducing early coronary reocclusion has been difficult to define.

METHODS AND RESULTS

In conscious dogs with coronary thrombosis induced by electrical current, we assessed the impact on the rapidity of thrombolysis and the incidence of reocclusion of two types of adjunctive treatment given concomitantly with intravenous tissue-type plasminogen activator (t-PA): 1) inhibition of platelet function with a peptide mimetic antagonist of platelet glycoprotein IIb/IIIa receptors or with lysine acetylsalicylic acid (ASA) and 2) inhibition of thrombin activity with recombinant hirudin or with heparin. ASA but not the receptor antagonist shortened the time to thrombolysis with t-PA (20 +/- 13 [mean +/- SD] minutes with ASA, 36 +/- 15 minutes with receptor antagonist, and 43 +/- 16 minutes with the saline control). Reocclusion occurred promptly after completion of the infusion of t-PA in all seven dogs given saline. Reocclusion was delayed and prevented in some dogs within 90 minutes after the end of the infusion of t-PA by both antiplatelet agents but still occurred in 42% despite continued inhibition of platelet function (i.e., three of six dogs given ASA and two of six given receptor antagonist). In contrast, inhibition of thrombin activity with recombinant hirudin in a dose that prolonged the partial thromboplastin time modestly (1.5-2-fold) resulted in accelerated lysis (19 +/- 10 minutes) and prevention of reocclusion in each of six dogs. Heparin given in doses that elicited similar prolongation of the partial thromboplastin time did not accelerate lysis nor prevent reocclusion, which occurred in five of six dogs.

CONCLUSIONS

Inhibition of thrombin by recombinant hirudin facilitates thrombolysis and maintains patency of coronary arteries recanalized with t-PA particularly effectively. The benefit conferred may reflect direct anticoagulant effects plus diminished activation of platelets secondary to decreased thrombin activity.
Prospective comparison of a conventional and an accelerated protocol for programmed ventricular stimulation in patients with coronary artery disease.
Authors: Morady F , Kadish A , de Buitleir M , Kou W H , Calkins H , Schmaltz S , Rosenheck S , Sousa J
Published: June 2012

BACKGROUND

This study compared the sensitivity, specificity, and efficiency of a "conventional" and "accelerated" programmed stimulation protocol in 293 patients with coronary artery disease who had a history of sustained or nonsustained monomorphic ventricular tachycardia (VT).

METHODS AND RESULTS

In the conventional protocol, one and two extrastimuli were introduced during sinus rhythm and during basic drive trains at cycle lengths of 600 and 400 msec at the right ventricular apex and then at the outflow tract or septum. In the accelerated protocol, one, two, and then three extrastimuli were introduced at each of three basic drive train cycle lengths (350, 400, and 600 msec) at the right ventricular apex; the procedure was repeated at a second right ventricular site. Six hundred thirty-four electrophysiological tests were performed using one of these two protocols either in the baseline state (293 tests) or during drug testing (341 tests). The yield of sustained, monomorphic VT was 89% with the conventional protocol and 92% with the accelerated protocol during baseline tests in patients who had a history of sustained VT (p = 0.05); 20% and 34%, respectively, during baseline tests in patients with a history of nonsustained VT (p = 0.06); and 70% and 77%, respectively, during drug testing (p = 0.2). To induce sustained, monomorphic VT, 10.1 +/- 5.0 (mean +/- SD) protocol steps and 14.4 +/- 8.7 minutes were required with the conventional protocol, compared with 4.0 +/- 3.7 steps and 5.6 +/- 6.1 minutes with the accelerated protocol (p less than 0.001 for each comparison). Among the tests in which sustained, monomorphic VT was induced, sustained polymorphic VT or ventricular fibrillation was induced more often with the conventional protocol (3.6%) than with the accelerated protocol (0.9%, p = 0.05).

CONCLUSIONS

The efficiency of programmed stimulation can be improved by the early use of a basic drive train cycle length of 350 msec and three extrastimuli. Compared with a conventional stimulation protocol, the accelerated protocol used in this study reduces the number of protocol steps and duration of time required to induce monomorphic VT by an average of more than 50% and improves the specificity of programmed stimulation without impairing the yield of monomorphic VT.
Prognostic significance of Doppler measures of diastolic function in cardiac amyloidosis. A Doppler echocardiography study.
Authors: Klein A L , Hatle L K , Taliercio C P , Oh J K , Kyle R A , Gertz M A , Bailey K R , Seward J B , Tajik A J
Published: June 2012

BACKGROUND

We have previously characterized the left ventricular diastolic filling abnormalities in cardiac amyloidosis by Doppler methods. The various filling patterns were shown to be related to the degree of cardiac amyloid infiltration. The purpose of this study was to determine the value of Doppler diastolic filling variables for assessing prognosis in cardiac amyloidosis.

METHODS AND RESULTS

We performed pulsed-wave Doppler studies of the left ventricular inflow and obtained clinical follow-up data in 63 consecutive patients with biopsy-proven systemic amyloidosis. All patients had typical echocardiographic features of cardiac involvement. The patients were subdivided into two groups according to deceleration time: Group 1 (33 patients) had a deceleration time of 150 msec or less, indicative of restrictive physiology, and group 2 (30 patients) had a deceleration time of more than 150 msec. Of the 63 patients, 32 (51%) died during a mean follow-up period of 18 +/- 12 months. Of these deaths, 25 (78%) were cardiac deaths, and 19 of the 25 patients (76%) were from group 1. The 1-year probability of survival in group 1 was significantly less than that in group 2 (49% versus 92%, p less than 0.001). Bivariate analysis revealed that the combination of the Doppler variables of shortened deceleration time and increased early diastolic filling velocity to atrial filling velocity ratio were stronger predictors of cardiac death than were the two-dimensional echocardiographic variables of mean left ventricular wall thickness and fractional shortening.

CONCLUSIONS

Doppler-derived left ventricular diastolic filling variables are important predictors of survival in cardiac amyloidosis.
Safety of transesophageal echocardiography. A multicenter survey of 10,419 examinations.
Authors: Daniel W G , Erbel R , Kasper W , Visser C A , Engberding R , Sutherland G R , Grube E , Hanrath P , Maisch B , Dennig K
Published: June 2012

BACKGROUND

During the past few years, transesophageal echocardiography (TEE) has been increasingly used in clinical cardiology; data concerning the practicability and safety of the technique, however, are rare.

METHODS AND RESULTS

This report analyzes the experience of 15 European centers performing TEE studies for at least 1 year. At the time of this survey, 10,419 TEE examinations had been attempted or performed in these institutions. These TEE examinations were carried out by 54 physicians, 53.7% of whom had been trained in endoscopic techniques. Within the same time period, 160,431 precordial echocardiographic examinations were performed in the 15 institutions; the ratio between TEE and transthoracic studies averaged 9.03 +/- 6.4% (range of the 15 centers, 1.4-23.6%). Of the 10,419 patients, 9,240 (88.7%) were conscious inpatients or outpatients at the time of the TEE examination; the vast majority of the conscious patients did not receive intravenous sedation before TEE. In 201 cases (1.9%), insertion of the TEE probe was unsuccessfully attempted because of a lack of patient cooperation and/or operator experience (98.5%) or because of anatomical reasons (1.5%). In 90 of 10,218 TEE studies (0.88%) with successful probe insertion, the examination had to be interrupted because of the patient's intolerance of the echoscope (65 cases); because of pulmonary (eight cases), cardiac (eight cases), or bleeding complications (two cases); or for other reasons (seven cases). One of the bleeding complications resulted from a malignant lung tumor with esophageal infiltration and was fatal (mortality rate, 0.0098%).

CONCLUSIONS

This multicenter survey documents that TEE studies are associated with an acceptable low risk when used by experienced operators under proper safety conditions.
Noninvasive quantification of regional myocardial blood flow in coronary artery disease with oxygen-15-labeled carbon dioxide inhalation and positron emission tomography.
Authors: Araujo L I , Lammertsma A A , Rhodes C G , McFalls E O , Iida H , Rechavia E , Galassi A , De Silva R , Jones T , Maseri A
Published: June 2012

BACKGROUND

Oxygen-15-labeled water is a diffusible, metabolically inert myocardial blood flow tracer with a short half-life (2 minutes) that can be used quantitatively with positron emission tomography (PET). The purpose of this study was to validate a new technique to quantify myocardial blood flow (MBF) in animals and to assess its application in patients.

METHODS AND RESULTS

The technique involves the administration of 15O-labeled carbon dioxide (C15O2) and rapid dynamic scanning. Arterial and myocardial time activity curves were fitted to a single tissue compartment tracer kinetic model to estimate MBF in each myocardial region. Validation studies consisted of 52 simultaneous measurements of MBF with PET and gamma-labeled microspheres in nine closed-chest dogs over a flow range of 0.5-6.1 ml/g/min. A good correlation between the two methods was obtained (y = 0.36 + 1.0x, r = 0.91). Human studies consisted of 11 normal volunteers and eight patients with chronic stable angina and single-vessel disease, before and after intravenous dipyridamole infusion. In the normal group, MBF was homogeneous throughout the left ventricle both at rest and after administration of dipyridamole (0.88 +/- 0.08 ml/g/min and 3.52 +/- 1.12 ml/g/min, respectively; p less than or equal to 0.001). In patients, resting MBF was similar in the distribution of the normal and stenotic arteries (1.03 +/- 0.23 and 0.93 +/- 0.21 ml/g/min, respectively). After dipyridamole infusion, MBF in normally perfused areas increased to 2.86 +/- 0.83 ml/g/min, whereas in the regions supplied by stenotic arteries it increased to only 1.32 +/- 0.27 ml/g/min (p less than or equal to 0.001).

CONCLUSIONS

PET with C15O2 inhalation provides an accurate noninvasive quantitative method for measuring regional myocardial blood flow in patients.
Acute coronary artery occlusion during and after percutaneous transluminal coronary angioplasty. Frequency, prediction, clinical course, management, and follow-up.
Authors: de Feyter P J , van den Brand M , Laarman G J , van Domburg R , Serruys P W , Suryapranata H , Jaarman G
Published: June 2012

BACKGROUND

Acute coronary artery occlusion after percutaneous transluminal coronary angioplasty (PTCA) continues to remain a serious complication despite significant improvement in operator performance and technological advancements. This retrospective study was performed to ascertain the frequency, predictive variables, management, and outcome of acute coronary artery occlusion.

METHODS AND RESULTS

The study was based on data from 1,423 consecutive patients who underwent an elective coronary angioplasty between January 1986 and December 1988. Acute coronary artery occlusion occurred in 104 patients (7.3%). Acute occlusion developed during the dilatation procedure in 80 patients (5.6%) and within 24 hours after the procedure in 24 patients (1.7%). Four clinical and 14 angiographic variables predictive for acute coronary artery occlusion were analyzed in these 104 patients with a complicated procedure and were compared with those in 104 representative patients with successful attempts. Multivariate analysis found three independent predictive variables: unstable angina, multivessel disease, and complex lesions. The overall clinical outcome after management of acute coronary artery occlusion including immediate repeat dilatation (95 patients), use of intracoronary streptokinase (34 patients), or autoperfusion catheter (12 patients) was successful (reduction of lumen diameter to less than 50%, no death, no myocardial infarction [MI], and no emergency surgery) in 42 patients (40%), was a failure without major complication in four patients (4%), and was a failure with major complication (death, MI, and emergency surgery) in 58 patients (56%). The overall mortality rate was 6% (six patients), the overall MI rate was 36% (37 patients), and emergency bypass surgery was required in 30% of patients (31 patients). At 6 months' follow-up of 42 patients with successful management, recurrent angina pectoris due to restenosis occurred in 10 patients (24%), and a late MI occurred in one patient (3%). At 6 months' follow-up of 56 survivors with unsuccessful management (development of MI or need for emergency bypass surgery), recurrent angina occurred in nine patients (16%), and cardiac death in two patients (4%). However, the majority of patients in both groups were either symptom free or had mild angina pectoris.

CONCLUSION

Acute coronary artery occlusion during PTCA is often unpredictable, but its frequency is higher in patients with unstable angina, multivessel disease, and complex lesions. Despite immediate redilatation, use of intracoronary streptokinase, and emergency bypass surgery, PTCA is associated with a high mortality and morbidity.
Giant cell versus lymphocytic myocarditis. A comparison of their clinical features and long-term outcomes.
Authors: Davidoff R , Palacios I , Southern J , Fallon J T , Newell J , Dec G W
Published: June 2012

BACKGROUND

Giant cell myocarditis has rarely been diagnosed premortem, and little is known about its natural history. In addition, no comparative studies with lymphocytic myocarditis exist.

METHODS AND RESULTS

The clinical features, serial change in left ventricular fraction (LVEF), and outcomes of all patients with histologically verified myocarditis were retrospectively evaluated. Ten patients (22%) were found to have giant cell myocarditis (group 1), whereas the remaining 36 (78%) had lymphocytic myocarditis (group 2). Age at presentation, gender distribution, duration of symptoms, initial LVEF, and resting hemodynamics did not differ between groups. Ventricular tachycardia was detected in 90% of group 1 patients compared with only 25% of group 2 (p = 0.0007). Atrioventricular block that required pacemaker insertion was also more common in group 1 (60%) than in group 2 (8.3%) (p = 0.001). Left ventricular systolic function declined during follow-up in group 1 patients (LVEF, 0.43 +/- 0.07-0.26 +/- 0.05, p = 0.11) but increased in group 2 patients (LVEF, 0.33 +/- 0.03-0.41 +/- 0.03, p = 0.02). When the net change between initial and final LVEF was assessed, a significant difference was evident (giant cell group, -0.17 +/- 0.06; lymphocytic group, +0.07 +/- 0.03; p = 0.0008). Although a greater proportion of patients in group 1 died or required transplantation (seven of 10 versus 11 of 36, p = 0.03), actuarial survival over 4 years was not different for the giant cell group (50%) than for the lymphocytic group (62%).

CONCLUSION

Giant cell myocarditis was more prevalent than previously recognized and highly associated with both ventricular tachycardia and pacemaker requirement. The likelihood of an adverse event, either cardiovascular mortality or cardiac transplantation, was significantly greater for patients with giant cell myocarditis than for those with lymphocytic myocarditis, perhaps because of the progressive decline in left ventricular systolic function that was observed in those with giant cell myocarditis.
Percutaneous balloon versus surgical closed commissurotomy for mitral stenosis. A prospective, randomized trial.
Authors: Turi Z G , Reyes V P , Raju B S , Raju A R , Kumar D N , Rajagopal P , Sathyanarayana P V , Rao D P , Srinath K , Peters P
Published: June 2012

BACKGROUND

We performed a prospective, randomized trial comparing percutaneous balloon commissurotomy with surgical closed commissurotomy in 40 patients with severe rheumatic mitral stenosis.

METHODS AND RESULTS

Data were analyzed by investigators who were masked to treatment assignment or phase of study. Patients randomized to balloon (n = 20) or surgical (n = 20) commissurotomy had severe mitral stenosis without significant baseline differences (left atrial pressure, 26.1 +/- 4.2 versus 27.6 +/- 6.2 mm Hg; mitral valve gradient, 18.0 +/- 4.2 versus 19.7 +/- 6.3 mm Hg; mitral valve area, 1.0 +/- 0.2 versus 1.0 +/- 0.4 cm2, respectively). At 1-week follow-up after balloon commissurotomy, pulmonary wedge pressure was 14.3 +/- 7.2 mm Hg; mitral valve gradient was 9.6 +/- 5.1 mm Hg; and mitral valve area was 1.6 +/- 0.6 cm2 (all p less than 0.0001). At 1-week follow-up after surgical closed commissurotomy, wedge pressure was 13.7 +/- 5.4 mm Hg; mitral valve gradient was 9.4 +/- 4.2 mm Hg (both p less than 0.0001); and mitral valve area was 1.6 +/- 0.7 cm2 (p less than 0.003). At 8-month follow-up, improvement occurred in both groups: Mitral valve area was 1.6 +/- 0.6 cm2 in the balloon commissurotomy group (p less than 0.002) and was 1.8 +/- 0.6 cm2 in the surgical closed commissurotomy group (p less than 0.0001). There was no difference between the groups at 1-week or 8-month follow-up (all p greater than 0.4). One case of severe mitral regurgitation occurred in each group; complications were otherwise related to transseptal catheterization. There was no death, stroke, or myocardial infarction. Cost analysis revealed that balloon commissurotomy may substantially exceed the cost of surgical commissurotomy in developing countries, whereas it may represent a significant savings in industrialized nations.

CONCLUSIONS

We conclude that percutaneous balloon commissurotomy and surgical closed commissurotomy result in comparable hemodynamic improvement that is sustained through 8 months of follow-up.
Relations between heart rate, ischemia, and drug therapy during daily life in patients with coronary artery disease.
Authors: McLenachan J M , Weidinger F F , Barry J , Yeung A , Nabel E G , Rocco M B , Selwyn A P
Published: June 2012

BACKGROUND

Previous studies have shown that little if any increase in heart rate occurs 1 minute before the onset of ischemia in ambulant patients with coronary artery disease. This study tested the hypothesis that there are characteristic relations between heart rate and ischemia in ambulant patients with coronary artery disease.

METHODS AND RESULTS

Twenty-one patients with proven coronary disease demonstrated 212 episodes of ischemia during 504 hours of continuous monitoring of the electrocardiogram. An important increase in heart rate (from 74 +/- 11 to 90 +/- 14 beats/min, p less than 0.001) occurred between 5 and 30 minutes (not 1 minute) before the onset of ischemia. A significantly higher heart rate at onset of ischemia was seen during Bruce protocol exercise testing than during daily life (117 +/- 12 versus 95 +/- 15 beats/min, p less than 0.01). However, when a less-strenuous, but more prolonged, exercise protocol was used in a subgroup of patients (n = 12), ischemia occurred at a heart rate that was significantly lower than during the Bruce protocol (88 +/- 14 versus 103 +/- 15 beats/min, p less than 0.05) and was not significantly different from the threshold heart rate at onset of ischemia during daily life (88 +/- 14 versus 84 +/- 12 beats/min, p = NS). As part of two placebo-controlled trials, treatment with both propranolol and nitroglycerin altered the distribution of ischemic events by heart rate but in opposite directions. Although propranolol largely eliminated events occurring at high (greater than 100 beats/min) and moderate (80-100 beats/min) heart rates, the number of events at low (less than 80 beats/min) heart rates was increased. In contrast, nitroglycerin reduced episodes at low and moderate heart rates only.

CONCLUSIONS

Important increases in heart rate occur before the onset of ischemia during daily life, but this increase occurs much earlier than has been reported. Duration of heart rate increase appears to influence the heart rate threshold for ischemia, and this may contribute to the occurrence of ischemia at lower heart rates during daily life than during standard exercise testing. Last, different classes of drugs appear to have characteristic effects on ischemia occurring at different heart rates that may be useful in planning therapy.
Low rate of treatment of hypercholesterolemia by cardiologists in patients with suspected and proven coronary artery disease.
Authors: Cohen M V , Byrne M J , Levine B , Gutowski T , Adelson R
Published: June 2012

BACKGROUND

Although specific guidelines for the treatment of hypercholesterolemia have been published, it is not known whether physicians treating patients likely to have lipid disorders have adopted the recommendations.

METHODS AND RESULTS

The approach of cardiologists to the treatment of hypercholesterolemia in a metropolitan teaching hospital was assessed by interviewing patients with chest pain who were admitted for coronary angiography in 1988-1989 and by measuring fasting blood lipid profiles. At 1 month and again 12-24 months later, patients were contacted by telephone to determine if there had been any changes in treatment. Of 95 patients evaluated, 81 had coronary artery disease. Only 17% of those with high levels of total cholesterol and/or low density lipoprotein cholesterol were being actively treated with diet and/or drugs. In the remaining patients, either lipid studies had not been done or abnormal results had not been addressed. There was little change in treatment approach during the month after the diagnostic procedure. Furthermore, the experience was similar in those patients subjected to coronary revascularization. One to 2 years after the initial intervention, 69 of the original study group could be contacted again. Although active dietary or pharmacological therapy was initiated in some individuals during this interval, it was stopped in others. Thirty-five percent of hypercholesterolemic patients were receiving targeted therapy.

CONCLUSIONS

Thus, only a small proportion of patients with documented coronary artery disease and hypercholesterolemia were being actively treated for their lipid disorder, suggesting that the published treatment guidelines have not yet been fully accepted. However, an encouraging improvement in frequency of treatment of hypercholesterolemia was documented during the 1-2-year observation period.
Hypertension in African-Americans.
Authors: Saunders E
Published: June 2012

A considerable disparity exists between African-Americans and US Caucasians in the incidence, severity, and management of hypertension. As a consequence, overall hypertension-related morbidity and mortality rates are at least threefold to fivefold higher in African-Americans than in Caucasians. Alarmingly high frequencies of stroke, end-stage renal disease, congestive heart failure, and left ventricular hypertrophy occur in African-Americans. To bring this crisis under control will require a renewed commitment to expanded research, improved public health measures, and more effective clinical intervention. Current hypertension control programs must be expanded and adequately funded. In addition, primary prevention of hypertension should be strongly recommended for the US population, especially African-Americans.
Hypertension in Hispanics, Asians and Pacific-Islanders, and Native Americans.
Authors: Martinez-Maldonado M
Published: June 2012

There is a paucity of information about hypertension and its risk factors, prevalence, morbidity, and mortality in many racial minorities in the United States. Most of the population groups discussed in this section are composed of several subgroups that differ culturally, socioeconomically, educationally, and ethnically. This fact, however, does not lessen the need for more information about the extent of hypertension and risk factors in these groups. Moreover, a bonus from expanded research in these areas will be new information useful to the general population.
Localization of gene for familial hypertrophic cardiomyopathy to chromosome 14q1 in a diverse US population.
Authors: Hejtmancik J F , Brink P A , Towbin J , Hill R , Brink L , Tapscott T , Trakhtenbroit A , Roberts R
Published: June 2012

BACKGROUND

Familial hypertrophic cardiomyopathy, an inherited primary cardiac abnormality characterized by ventricular hypertrophy, is the leading cause of sudden death in the young. Recent application of restriction fragment length polymorphism markers has provided provocative results, with localization to chromosome 18 (Japanese studies), 16 (Italian studies), 14 (US and French-Canadian studies), and two (National Institutes of Health studies) indicating genetic heterogeneity. Interpretation remains speculative until at least one of these loci is confirmed in unrelated pedigrees by independent investigators.

METHODS AND RESULTS

We studied eight unrelated families of varied ethnic origins across the United States. DNA from each individual was digested with restriction enzymes TaqI or BamHI and analyzed by Southern blots followed by hybridization with probes T cell receptor alpha (TCRA), myosin heavy chain beta, D14S25, and D14S26. Multipoint linkage analysis showed a maximum lod score of 4.3, placing the locus 10 cM from D14S26 between D14S26 and TCRA, with an odds ratio of 20,000:1 and 90% confidence limits of 12 cM proximal to D14S25 to 4 cM distal to TCRA. The probability of linkage to 14q1 was more than 99%.

CONCLUSIONS

These results indicate that the loci for familial hypertrophic cardiomyopathy in our families is primarily 14q1 but does not exclude other loci in a small proportion of the families. Thus, 14q1 appears to be the locus for familial hypertrophic cardiomyopathy in a significant proportion of the US population.
Effects of asymptomatic ischemia on long-term prognosis in chronic stable coronary disease.
Authors: Yeung A C , Barry J , Orav J , Bonassin E , Raby K E , Selwyn A P
Published: June 2012

BACKGROUND

Ischemia on ambulatory electrocardiographic monitoring has been shown to adversely affect short-term prognoses in patients with unstable angina, after myocardial infarction, and with chronic stable angina.

METHODS AND RESULTS

In this long-term study, we followed 138 patients (mean age, 59 +/- 9 years) with chronic stable angina and positive exercise tests for cardiac events (e.g. death, myocardial infarction, percutaneous transluminal coronary angioplasty, or coronary artery bypass graft surgery). In 105 patients, ambulatory electrocardiographic monitoring was performed after all antianginal medication was withheld for 48 hours. In 26 patients, the diagnostic tests were repeated while on their usual medication. In addition to the 105 patients, 33 patients had their monitoring performed only while on their usual medication. During 37 +/- 17 months of follow-up, there were nine deaths, nine myocardial infarctions, and 35 revascularization procedures. In patients monitored off medication, Cox survival analysis showed that the occurrence of ischemia on electrocardiographic monitoring was the most significant predictor of death and myocardial infarction in the subsequent 2 years (p = 0.02) and all adverse events for 5 years (p = 0.009). Patients who were monitored on medication and did not have ischemia (n = 18) appeared to have more adverse events than patients who had no ischemia while being monitored off medication (n = 43).

CONCLUSIONS

Asymptomatic ischemia on ambulatory electrocardiographic monitoring in patients with stable angina predicts death and myocardial infarction for 2 years and all adverse events for 5 years. Monitoring performed while on medication may show no ischemia; however, this may not indicate low risk of future coronary events.
Noninvasive identification of myocardium at risk in patients with acute myocardial infarction and nondiagnostic electrocardiograms with technetium-99m-Sestamibi.
Authors: Christian T F , Clements I P , Gibbons R J
Published: June 2012

BACKGROUND

Patients who have chest pain without electrocardiographic ST elevation are not candidates for thrombolytic therapy in most clinical trials. This study examined the value of technetium-99m-Sestamibi tomographic imaging to assess myocardial perfusion in patients during chest pain without ST elevation.

METHODS AND RESULTS

Tc-99m-Sestamibi was injected in 14 patients who had chest pain without ST elevation, who subsequently developed enzymatic evidence of myocardial infarction within 24 hours. Tomographic imaging was performed 1-6 hours after injection. Thirteen of 14 patients showed significant perfusion defects indicative of acute myocardial infarction consistent with absent perfusion (20 +/- 15% of the left ventricle; range, 2-53%); one patient had normal images. Because of the absence of definitive electrocardiographic changes, only five patients received reperfusion therapy within 6 hours of the onset of chest pain. Regional wall motion abnormalities were present in nine of nine patients undergoing contrast ventriculography and correlated with the location of the Tc-99m-Sestamibi perfusion defect. At the time of subsequent coronary angiography, total arterial occlusion was present in 11 of the 14 patients. The infarct-related artery could be identified in 13 of the 14 patients. In six of these 13 patients, the left circumflex was the infarct-related artery.

CONCLUSIONS

Patients who have chest pain without electrocardiographic ST elevation may have arterial occlusion and significant myocardium at risk. Tc-99m-Sestamibi imaging may be of benefit in identifying these patients early so that they can be considered for acute reperfusion therapy.
Anatomic correlates of aortic pulse wave velocity and carotid artery elasticity during atherosclerosis progression and regression in monkeys.
Authors: Farrar D J , Bond M G , Riley W A , Sawyer J K
Published: June 2012

We noninvasively measured changes in average aortic stiffness in 79 cynomolgus monkeys being fed cholesterol progression, regression, and control diets by measuring pulse wave velocity (PWV) in 260 experiments during a 30-month period. Every 6 months, a group of monkeys was studied with invasive aortic PWV techniques and with ultrasonically determined pressure-strain elastic modulus (Ep) of the carotid artery, and then the group was killed so that morphometric evaluation of atherosclerosis severity could be made. After 6 months of a cholesterol progression diet, PWV decreased slightly from 6.2 +/- 0.1 to 5.7 +/- 0.1 m/sec, followed by an approximate linear increase to 8.8 +/- 1.2 m/sec after 30 months on the diet. The corresponding ratio of intimal (plaque) area to medial area (IA/MA) measured on perfusion-fixed cross-sections of the abdominal and thoracic aortas increased from 0.16 +/- 0.07 at 6 months to 1.23 +/- 0.22 at 30 months. Monkeys in the regression groups were fed the cholesterol progression diet for 18 months, followed by a chow diet for 6 or 12 months. In the first 6 months of the cholesterol regression diet, PWV continued to increase from 7.0 +/- 0.2 to 8.1 +/- 0.4 m/sec, and IA/MA was 1.24 +/- 0.18. However, after 12 months of the cholesterol regression diet, PWV decreased to 6.8 +/- 0.4 m/sec, and IA/MA was 0.90 +/- 0.18. The variability of the data demonstrates that PWV is not a simple function of atherosclerosis severity, and the best simple correlation was r = 0.69 (r2 = 0.48) between PWV and intimal area. However, multiple regression analysis of aortic PWV, systolic (SP) and diastolic (DP) blood pressures, and total plasma cholesterol concentration (TPC), all of which can be measured with minimally invasive techniques, improved the prediction of the IA/MA ratio through the following equation: IA/MA = 0.127 PWV-0.039 DP+0.023SP+0.0003TPC-0.292 (r = 0.81, r2 = 0.66). These data suggest that arterial stiffness in combination with minimally invasive parameters can be used to predict the severity of diffuse asymptomatic atherosclerosis in monkeys. However, more widespread application of these data to humans is uncertain because of biological variability and differences between animal models and human subjects.