bluuebunny/crossref_metadata_2025 huggingface dataset:
"Intramural" residual interventricular defects after repair of conotruncal malformations.
Authors: Preminger T J , Sanders S P , van der Velde M E , Castañeda A R , Lock J E
Published: June 2012

BACKGROUND

We report an unusual type of residual interventricular communication in patients with conotruncal malformations in which the aorta is completely or partly aligned with the right ventricle (RV). Interventricular communications after surgical repair usually result from additional defects, patch dehiscence, or incomplete closure and lie in the septal plane. However, after a right ventricular aorta is baffled to the left ventricle, the ventricular septal defect (VSD) patch and RV free wall form part of the systemic outflow tract. This "neo-left ventricular" outflow tract may provide a location for residual interventricular communications out of the septal plane.

METHODS AND RESULTS

We reviewed echocardiographic, angiographic, and clinical records of patients who had one or more residual interventricular communications out of the plane of the ventricular septum after repair of a conotruncal anomaly. Between June 1990 and October 1992, we observed such defects in eight patients, 5 to 26 years old, after repair of double-outlet right ventricle (n = 6), tetralogy of Fallot (n = 1), or truncus arteriosus (n = 1). In each, the VSD patch was anchored to the RV free wall near the aortic root. Nonetheless, channels were observed around the edge of the patch, between the neo-systemic outflow tract and the right ventricle. All patients had right ventricular hypertension; in seven, the pulmonary-to-systemic flow ratio (Qp:Qs) was > or = 2. At multiple unsuccessful reoperations (two to four per patient), the patch edges appeared securely attached to myocardium. Angiographic views profiling the septum failed to localize these defects, since they are not in the native septum. Echocardiographic detection of such anterior defects can be difficult. Transcatheter umbrella closure was attempted in the seven patients with large shunts; success was limited by the multiplicity of flow channels. Umbrella closure eliminated the need for further reoperation in four of seven patients, one patient died suddenly awaiting reoperation, and two deaths followed reoperation.

CONCLUSIONS

"Intramural" residual interventricular defects are difficult to diagnose by all modalities. Umbrella placement may reduce the left-to-right shunt. Successful surgical closure may require removal and reattachment of the anterior portion of the patch.
Intravascular ultrasound of coronary arteries in children. Assessment of the wall morphology and the lumen after Kawasaki disease.
Authors: Sugimura T , Kato H , Inoue O , Fukuda T , Sato N , Ishii M , Takagi J , Akagi T , Maeno Y , Kawano T
Published: June 2012

BACKGROUND

The long-term clinical issue in Kawasaki disease (KD) concerns the coronary artery lesion. Two-dimensional echocardiography and coronary angiography are routine examinations to evaluate the coronary lesions; however, these are not adequate to assess the wall morphology of the coronary artery (CA). Intravascular ultrasound imaging (IVUS), a new technology for the evaluation of the coronary artery lumen and wall morphology in vivo, was performed for patients after KD in their long-term follow-up, and we examined the new insights it gave.

METHODS AND RESULTS

IVUS was performed during cardiac catheterization in 20 subjects (10 patients after KD who still had coronary aneurysms or regressed coronary aneurysms, 2 after KD who had no coronary abnormal lesion, and 8 control patients with congenital heart disease and normal CA). We evaluated the wall structure at 10 to 15 sites of the CA in each patient. IVUS was performed with a commercially available ultrasound imaging catheter. Four sites of a CA aneurysm in KD demonstrated a markedly dilated lumen without thickened intima. One site of a CA aneurysm with calcification demonstrated an asymmetrical lumen by a dense echo with acoustic shadows. Twenty-two sites of a regressed CA aneurysm demonstrated a marked symmetrical or asymmetrical thickening of the intima with a dense echo, in which the size of the lumen was similar to that at a site near a regressed aneurysm. The sites of angiographically normal CA revealed normal structures and a thin intima in many instances. Nine of 28 sites in KD with a CA abnormal lesion, particularly near a coronary aneurysm or regressed aneurysm, demonstrated a mild thickening of the intima. All the 10 sites in KD without a CA abnormal lesion and all the 25 sites in patients with congenital heart disease with normal CA demonstrated a smooth intima.

CONCLUSIONS

This study demonstrated that the site of a regressed coronary aneurysm has a markedly thickened but smooth intima. The sites of angiographically normal CA after KD with or without a coronary lesion demonstrated normal IVUS findings in most instances but in some cases revealed a mild intimal thickening. IVUS is useful to evaluate the CA wall morphology and may contribute to the assessment of long-term CA sequelae and the possible development of arteriosclerotic changes in KD.
Increased vascular responsiveness to norepinephrine in rats with heart failure is endothelium dependent. Dissociation of basal and stimulated nitric oxide release.
Authors: Teerlink J R , Gray G A , Clozel M , Clozel J P
Published: June 2012

BACKGROUND

Endothelial dysfunction and abnormal vascular responsiveness to vasoconstrictors may play an important role in chronic heart failure (CHF). The purpose of our study was to (1) evaluate whether the vascular response to norepinephrine is abnormal in a rat model of heart failure; (2) investigate the role of alpha 1- and alpha 2-adrenergic receptors; and (3) assess the contribution of the endothelium, and specifically endothelium-derived nitric oxide, to this response.

METHODS AND RESULTS

Concentration-response curves of rat thoracic aortic rings were studied in isolated organ baths at 1 week after coronary artery ligation. In CHF rats, norepinephrine-induced contractions were increased in intact rings compared with rings from sham rats, despite decreased contraction in denuded rings. Decreased alpha 1-receptor sensitivity was demonstrated by the increased EC50 of methoxamine in endothelium-denuded rings from CHF rats, although maximal responses to KCl contraction were also decreased in CHF. There was no difference in the vascular response to clonidine, and acetylcholine-mediated relaxations were preserved in CHF rats, suggesting normal stimulated nitric oxide release. However, nitric oxide synthase inhibition with N omega-nitro-L-arginine methyl ester, as well as measurements of basal cGMP, demonstrated that basal nitric oxide release was decreased in CHF rats.

CONCLUSIONS

This study demonstrates that the increased vascular responsiveness to norepinephrine in intact vessels from rats with heart failure is the result of decreased basal nitric oxide release and suggests that the dissociation of basal and stimulated nitric oxide release may play a pathophysiology role at an early stage of heart failure.
Interaction of acute ventricular dilatation and d-sotalol during sustained reentrant ventricular tachycardia around a fixed obstacle.
Authors: Reiter M J , Zetelaki Z , Kirchhof C J , Boersma L , Allessie M A
Published: June 2012

BACKGROUND

Antiarrhythmic therapy of ventricular tachycardia is associated with decreased efficacy and increased proarrhythmia in patients with congestive heart failure, but the explanation for these observations is not known. This study examined the interaction of ventricular dilatation and d-sotalol in a model of reentry ventricular tachycardia.

METHODS AND RESULTS

Thin epicardial layers of anisotropic myocardium were created in Langendorff-perfused rabbit left ventricles by a cryo procedure. A fluid-filled, latex balloon was secured within the left ventricle to change ventricular volume. Sustained reentrant ventricular tachycardia, around a central cryolesion, was induced by rapid pacing in all preparations (n = 7). Epicardial mapping was performed through 248 electrodes. Single premature beats introduced within the reentry circuit were used to define the excitable gap. Dilatation did not influence ventricular tachycardia cycle length or conduction velocity. A 1.25-mL increase in left ventricular volume widened the excitable gap by 12% (range, 5% to 29%) (P < .001) because of a decrease in myocardial refractoriness. d-Sotalol (final concentration, 10 mg/L) narrowed the excitable gap 18% (range, 7% to 29%) (P = .002) in the undilated left ventricle. d-Sotalol was less effective in the dilated left ventricle, narrowing the excitable gap only 9%, a difference that was not statistically significant. During pacing to induce or terminate tachycardia, tachycardia acceleration was observed significantly more frequently in the dilated than in the undilated ventricle. Ventricular tachycardia acceleration was due to the development of double-wave reentry (two successive waves traveling in the same circuit in the same direction). d-Sotalol, which narrowed the excitable gap, prevented tachycardia acceleration and double-wave reentry.

CONCLUSIONS

Antiarrhythmic efficacy may be decreased by dilatation because of widening of the initial excitable gap and a decrease in the gap-narrowing effect of these agents. Double-wave reentry, more likely with a widening of excitable gap, may partially explain tachycardia acceleration in the dilated ventricle.
History of drugs for thrombotic disease. Discovery, development, and directions for the future.
Authors: Mueller R L , Scheidt S
Published: June 2012

The history of the antithrombotic agents--aspirin, heparin, warfarin, and the thrombolytics--is a rich and lively odyssey of serendipity, perseverance, vision, and conflict involving a number of striking personalities. The history of aspirin spans ages and continents from Hippocrates' analgesic for women in labor to the rediscovery of the white willow bark by English country scholar Reverend Edward Stone. Bayer chemist Felix Hoffmann reinvented aspirin for his ailing father; suburban physician L.L. Craven pioneered the prophylactic antithrombotic uses of aspirin; and Sir John Vane elucidated aspirin's mechanism of action as the inhibition of prostaglandin synthetase. Heparin was discovered by McLean, working as a medical student in 1915 in search of a pure procoagulant in dog liver. His original impure material differed somewhat from today's heparin, but purified heparin was rapidly accepted for a myriad of clinical uses; to this day, diverse new properties of this complex glycosaminoglycan continue to be elucidated. The oral anticoagulants emerged from veterinary research in the 1920s on a hemorrhagic disorder afflicting cattle that consumed spoiled sweet clover hay. Several chance encounters led Karl Link and his University of Wisconsin team to the identification of dicumarol as the offending agent in 1939 and its widespread therapeutic use by Wright and others in the 1940s. Link later developed warfarin as a rodenticide, but its use in humans soon followed in the 1950s. Vitamin K was discovered in the 1930s; its involvement in the mechanism of the anticoagulant agents was not delineated until the 1970s. The intrinsic ability of clotted blood to liquify and the fibrinolytic properties of normal urine were noted in the 1800s. Tillett and Sherry's group stumbled on the fibrinolytic properties of streptokinase in the 1930s and pioneered the therapeutic use of streptokinase in the 1940s and of urokinase in the 1960s. Several teams found tissue-type plasminogen activator in various body sites beginning in the 1940s, leading to its cloning and widespread use in the 1980s; anisoylated plasminogen-streptokinase activator complex is an example of rational drug design. The discoverers of these diverse agents have not only provided physicians with a potent armamentarium of antithrombotic drugs but also helped elucidate much basic science and vividly demonstrated the merits of perseverance, independent thought, and adherance to the scientific method.
The impending crisis awaiting cardiac transplantation. Modeling a solution based on selection.
Authors: Stevenson L W , Warner S L , Steimle A E , Fonarow G C , Hamilton M A , Moriguchi J D , Kobashigawa J A , Tillisch J H , Drinkwater D C , Laks H
Published: June 2012

BACKGROUND

Each month, the number of transplant candidates added to the waiting list exceeds the number of transplantations performed, and many outpatients deteriorate to require transplantation urgently. The current list of 2400 candidates and the average wait of 8 months continue to increase.

METHODS AND RESULTS

To determine the size at which the outpatient and critical candidate pools will stabilize, population models were constructed using current statistics for donor hearts, candidate listing, sudden death, and outpatient decline to urgent status and revised to predict the impact of alterations in policies of candidate listing. If current practices continue, within 48 months the predicted list will stabilize as the sum of an estimated 270 hospitalized candidates, among whom, together with newly listed urgent candidates, all hearts will be distributed and 3700 outpatient candidates with virtually no chance of transplantation unless they deteriorate to an urgent status. Decreasing the upper age limit now to 55 years would reduce the number listed each month by 30% and result within 48 months in a list of only 1490. The list could also be decreased by 30%, however, if it were possible to list only a candidate group with an 80% chance (compared with 52% estimated currently) of sudden death or deterioration during the next year. With this strategy, the waiting list would equilibrate within 48 months to one-third the current size, with 50% of hearts for outpatient candidates, who would then have an 11% chance each month of receiving a heart compared with 0% if recent policies prevail. Total deaths, with and without transplantation, would be minimized by this rigorous selection of outpatient candidates.

CONCLUSIONS

This study implies that immediate provisions should be made to limit candidate listing and revise expectations to reflect the diminishing likelihood of transplantation for outpatient candidates. Future emphasis should be on improved selection of candidates at highest risk without transplantation.
Exercise training confers anticipatory protection from sudden death during acute myocardial ischemia.
Authors: Hull S S , Vanoli E , Adamson P B , Verrier R L , Foreman R D , Schwartz P J
Published: June 2012

Seven conscious dogs documented to be at high risk by the occurrence of ventricular fibrillation (VF) during acute myocardial ischemia were randomly assigned to 6 weeks of either daily exercise training or cage rest followed by exercise training. After 6 weeks of daily treadmill training, heart rate variability, a marker of vagal tone, increased by 74% (P < .001); baroreflex sensitivity, a marker of the capability to reflexly augment vagal activity, increased by 69% (P < .01); the repetitive extrasystole threshold, a marker of ventricular electrical stability, increased by 44% (P < .05). After exercise training, the incidence of ventricular fibrillation during acute myocardial ischemia decreased by 100%, as all animals survived. Neither passage of time nor heart rate level during ischemia contributed to the outcome. The most likely mechanism to explain the striking change in risk status is the shift in autonomic balance characterized by increased cardiac vagal activity, which was previously shown to have an antifibrillatory effect. These results suggest that exercise training in healthy individuals may decrease their likelihood of developing lethal arrhythmias during acute myocardial ischemia.
Oral verapamil inhibits platelet thrombus formation in humans.
Authors: L-Lacoste L , Lam J Y , Hung J , Waters D
Published: June 2012

BACKGROUND

Calcium antagonists such as verapamil are potent coronary and systemic vasodilators that are used in the treatment of coronary disease. They have also been shown to inhibit platelet aggregation in vitro, but whether they have beneficial antithrombotic effects in humans is unclear, and whether they can potentiate the antithrombotic effects of aspirin is unknown.

METHODS AND RESULTS

Platelet thrombus formation and whole blood platelet aggregation were measured in 18 stable coronary patients on three separate occasions: at baseline when receiving no active medications, after 7 days of receiving oral verapamil SR (240 mg/d), and after 7 days of receiving a combination of oral verapamil SR and aspirin (325 mg/d). Thrombus formation on porcine aortic media that were placed into cylindrical flow chambers and exposed to flowing antecubital venous blood for 3 minutes was assessed morphometrically at a shear rate of 2546 s-1, which is typical of arterial flow at sites of stenoses. Thrombus formation under basal conditions was 7.0 +/- 1.6 microns 2, and this was decreased to 3.1 +/- 0.5 microns 2 (P < .05) after 7 days of treatment with oral verapamil SR and to 2.6 +/- 0.5 microns 2 (P < .05) after 7 days of treatment with oral verapamil and aspirin. Whole blood platelet aggregation levels in response to 0.050 and 0.075 U of thrombin at baseline were 10.8 +/- 1.0 and 11.9 +/- 1.0 omega; aggregation was inhibited after 7 days of treatment with verapamil to 6.5 +/- 1.1 and 7.8 +/- 0.9 omega (P < .05 versus baseline) and after 7 days of treatment with verapamil and aspirin to 6.1 +/- 1.1 and 7.2 +/- 1.0 omega (P < .05), respectively.

CONCLUSIONS

The present study demonstrates that part of the benefit of verapamil in ischemic heart disease may occur by inhibition of platelet aggregation and thrombus formation. This beneficial antithrombotic effect may be important in preventing acute coronary ischemic events resulting from thrombus formation at sites of plaque rupture.
A prospective study of the health effects of alcohol consumption in middle-aged and elderly men. The Honolulu Heart Program.
Authors: Goldberg R J , Burchfiel C M , Reed D M , Wergowske G , Chiu D
Published: June 2012

BACKGROUND

The study objective was to determine the association between reported alcohol consumption and total mortality, mortality from selected causes, and incident nonfatal chronic disease events in middle-aged (51 to 64 years old) and elderly (65 to 75 years old) men during an approximate 15-year follow-up period.

METHODS AND RESULTS

We conducted a prospective epidemiological study of Japanese-American men who were participating in the Honolulu Heart Program and were free from coronary heart disease, cerebrovascular disease, and cancer at baseline examination and at subsequent reexamination 6 years later. Self-reported alcohol consumption was determined twice: at the baseline examination in 1965 through 1968 and at reexamination approximately 6 years later (1971 through 1974). Four primary alcohol consumption groups who reported similar alcohol intake at the time of these two clinical examinations were considered: abstainers and light (1 to 14 mL of alcohol per day), moderate (15 to 39 mL of alcohol per day), and heavy (> or = 40 mL of alcohol per day) drinkers. Study end points were also determined in very light (1 to 4.9 mL of alcohol per day) drinkers and in men who reported a change in their alcohol intake between examinations. Longitudinal follow-up was carried out through the end of 1988 with determination of selected fatal and nonfatal events according to alcohol intake. After controlling for several potentially confounding factors, total mortality exhibited a J-shaped pattern in relation to alcohol consumption in middle-aged and elderly men. There was a trend for lower rates of occurrence of combined fatal and nonfatal coronary heart disease events with increasing alcohol consumption in both middle-aged and elderly men. Increasing alcohol consumption was related to an increased risk of fatal and nonfatal strokes in middle-aged men, whereas elderly light and moderate drinkers were at increased risk for fatal and nonfatal strokes. Heavy drinkers were at increased risk for fatal and nonfatal malignant neoplasms in the two age groups examined.

CONCLUSIONS

The results of this long-term prospective study provide a balanced perspective of the health effects of alcohol consumption in middle-aged and elderly men. High levels of alcohol consumption were shown to be related to an increasing risk of diseases of considerable public health importance. These findings suggest that caution be taken in formulating population-wide recommendations for increases in the population levels of alcohol consumed given the associated significant social and biological problems of high consumption levels.
Identification of coronary artery stenoses and poststenotic blood flow patterns using a miniature high-frequency epicardial transducer.
Authors: Kenny A , Shapiro L M
Published: June 2012

BACKGROUND

Intraoperative epicardial coronary Doppler ultrasound has the potential to provide anatomic and functional information. This technique has been hindered by the large size of standard transducers, but a miniature transducer is available that may fulfill the potential of coronary ultrasound.

METHODS AND RESULTS

Twenty consecutive patients who were undergoing coronary artery bypass grafting were studied and compared with 9 control patients with normal coronary arteries who were undergoing routine mitral valve surgery. A miniature 6.5-MHz transducer was used to image coronary arteries and measure coronary blood flow velocities. Seventeen proximal left anterior descending and 3 right coronary artery stenoses were studied. As defined by coronary angiography (1 to 34 days before surgery), there were 13 severe stenoses (> 70%), 4 moderate stenoses (40% to 70%), 2 minor stenoses (< 40%), and 1 subtotal occlusion. Stenoses were readily identified by ultrasound. Color flow mapping demonstrated laminar flow in normal arteries and nonlaminar flow across moderate and severe stenoses. In the control patients with unobstructed arteries, peak and mean diastolic velocities were 35 +/- 2.1 and 26 +/- 1.9 cm/s with peak and mean systolic velocities of 16 +/- 1.4 and 11 +/- 0.8 cm/s, respectively. Prestenotic flow velocities were not significantly different from normal control values, but a wide range of poststenotic flow disturbances were detected. Analysis of the 20 study patients did not reveal significant differences in poststenotic compared with prestenotic flow. A subgroup analysis of 12 patients with severe left anterior descending coronary artery stenoses was performed, and reversed poststenotic systolic flow was seen in 9. Prestenotic peak and mean systolic velocities were 16.5 +/- 1.7 and 11.9 +/- 1.1 cm/s, respectively, and were significantly altered downstream of the stenoses at -22.7 +/- 17.2 and -15.9 +/- 10.9 cm/s (P < .05 and P < .01, respectively). Reversed systolic flow was seen only distal to severe left anterior descending coronary artery stenoses and did not correlate with retrograde collateral filling as determined by preoperative coronary angiography. Moderate stenoses appeared to increase both systolic and diastolic components of poststenotic flow.

CONCLUSIONS

Epicardial Doppler ultrasound with a miniature transducer identifies coronary stenoses and associated blood flow disturbances. Compared with moderate lesions, severe stenoses demonstrated different poststenotic flow patterns. Intraoperative use of this technique may determine the hemodynamic significance of coronary stenoses.
Chronic dynamic exercise improves a functional abnormality of the G stimulatory protein in cardiomyopathic BIO 53.58 Syrian hamsters.
Authors: Tomita T , Murakami T , Iwase T , Nagai K , Fujita J , Sasayama S
Published: June 2012

BACKGROUND

The effects of chronic exercise training on myocardial contractility and beta-adrenergic signal transduction in hearts with left ventricular dysfunction have not been determined.

METHODS AND RESULTS

Fourteen-week-old cardiomyopathic BIO 53.58 and normal F1B Syrian hamsters underwent 10 weeks of treadmill training and were compared with 24-week-old BIO 53.58 and F1B untrained controls. Left ventricular isovolumic maximum positive dP/dt and peak developed pressure were significantly lower in BIO 53.58 than in F1B controls. Exercise training improved left ventricular contractile indices in BIO 53.58 but not F1B hamsters. The left ventricular beta-adrenergic receptor number (Bmax) was similar in BIO 53.58 and F1B controls. Basal adenylate cyclase activity (ACA) and ACAs stimulated by isoproterenol, 5'-guanylylimidodiphosphate (GppNHp), sodium fluoride, and forskolin were significantly lower in BIO 53.58 than in F1B controls. The functional activity of stimulatory guanine nucleotide-binding protein (Gs), as determined by reconstitution with S49 lymphoma cyc- cell membranes, was significantly lower in BIO 53.58 controls. After 10 weeks of exercise training, Bmax and basal and isoproterenol-stimulated ACAs were unchanged in either BIO 53.58 or F1B hamsters compared with controls. However, in F1B hamsters, training decreased ACAs stimulated by GppNHp, sodium fluoride, and forskolin, with a reduced functional activity of Gs. In contrast, these ACAs increased significantly in association with an enhanced Gs activity in cardiomyopathic BIO 53.58 hamsters after training.

CONCLUSIONS

Chronic exercise training does not change receptor-mediated beta-adrenergic responsiveness in either F1B or BIO 53.58 hamsters. However, exercise training reduces Gs activity in normal F1B hamsters and improves the functional abnormality of Gs in cardiomyopathic BIO 53.58 hamsters. This improvement may potentially contribute to augmented left ventricular contractility in BIO 53.58 after training.
Mapping of reset of anatomic and functional reentry in anisotropic rabbit ventricular myocardium.
Authors: Boersma L , Brugada J , Kirchhof C , Allessie M
Published: June 2012

BACKGROUND

Premature stimulation is used to characterize the reentrant circuit during ventricular tachycardia (VT) in patients. The goal of this study was to compare the effects of premature stimulation on functional and anatomic reentrant VT.

METHODS AND RESULTS

In 18 Langendorff-perfused rabbit hearts, thin layers of anisotropic left ventricular subepicardium were created by a cryoprocedure. In 8 hearts, rapid pacing induced reentry around a line of functional conduction block; in 10 hearts, reentry occurred around a fixed epicardial obstacle created by a cryoprobe. The cycle lengths (CL) of functional and anatomic VT were 110 +/- 10 and 167 +/- 17 milliseconds, respectively. During anatomic VT, the excitable gap measured 43% of the CL and premature stimuli could always reset VT (44 +/- 12 milliseconds). During early premature beats, conduction of the orthodromic wave was slightly depressed, but anatomic VT was never terminated. Reset curves at different sites in the ventricle revealed three different response types, both determined by and characterizing the spatial and temporal relation between pacing and recording sites. Premature stimulation during functional VT revealed a local excitable gap at the pacing site measuring 27% of the cycle length of VT. However, in only 3 of 8 hearts, premature stimuli could reset functional VT by 8%. In 5 VTs, advancement of the paced activation was fully compensated by prolongation of the return cycle, and VT was not reset. Due to slow conduction both toward and inside the circuit, the paced orthodromic wave lost its prematurity already within a distance of 6 to 10 mm from the pacing site.

CONCLUSIONS

Both during anatomic and functional reentry, an excitable gap is present in the reentrant circuit. Three different response curves reveal the localization of the pacing and recording sites in the circuit. Anatomic VT can always be reset by premature stimuli, whereas in 5 of 8 hearts, functional VT could not be reset. In the other 3 hearts, VT could only be reset for less than 7% to 11% of the VT interval. Therefore, it seems very unlikely that clinical VT based on functional reentry can be reset.
Major clinical events after coronary stenting. The multicenter registry of acute and elective Gianturco-Roubin stent placement. The Gianturco-Roubin Intracoronary Stent Investigator Group.
Authors: Sutton J M , Ellis S G , Roubin G S , Pinkerton C A , King S B , Raizner A E , Holmes D R , Kereiakes D J , Topol E J
Published: June 2012

BACKGROUND

Abrupt vessel closure and early reocclusion remain the principal vascular events underlying early recurrent ischemia complicating elective percutaneous transluminal coronary angioplasty (PTCA). Intracoronary stenting has been used to circumvent emergency bypass surgery after acute vessel closure and as an adjunct for the elective treatment of restenosis. The initial multicenter experience with the Gianturco-Roubin stent is presented, and predictors for early recurrent ischemic events are identified.

METHODS AND RESULTS

Data accrued from 639 serial patients undergoing emergency stenting for abrupt closure (n = 415; 65%) or elective deployment for restenosis (n = 224; 35%) from October 1989 through May 1991 were analyzed. The incidence of subsequent ischemic events, including death, nonfatal myocardial infarction, and bypass surgery referral within 90 days of the procedure, was higher after acute deployment (20%) compared with elective stenting (9%; P = .0004). Although mortality within the two cohorts was the same (3%; P = NS), there were significant differences in the incidence of nonfatal myocardial infarction (5% versus 0.5%; P = .002) and bypass surgery (12% versus 6%; P = .02) between the acutely and electively stented patients, respectively. These events were significantly more common when the stent was undersized to the target vessel diameter (stent:artery ratio for event, 0.95 +/- 0.14 versus no event, 1.04 +/- 0.22; P = .0001) or when there was less expansion of the lesion by the deployed device (stent-to-lesion diameter ratio for event, 6.6 +/- 9.2 versus no event, 11.0 +/- 21.4; P = .0001). In a stepwise logistic regression model, acute stenting (odds ratio [OR], 1.8; 95% confidence interval [CI], 1.3 to 2.4), multivessel disease (OR, 1.4; CI, 1.1 to 1.8), larger target lesion diameter (OR, 2.1; CI, 1.4 to 3.2), larger target vessel (OR, 2.9; CI, 1.7 to 4.7), and smaller stent size (OR, 6.1; CI, 3.0 to 12.3) were independent predictors of early, recurrent ischemic events. The presence of thrombus was associated with a higher event rate after elective stenting (OR, 2.3; CI, 1.06 to 5.4) but was not associated with a higher early event rate after acute stenting.

CONCLUSIONS

Early ischemic events are more common after acute stenting for abrupt or threatened closure than after elective deployment. These events may be avoided with careful attention to morphometric characteristics to avoid undersizing the stent to the target vessel and ensure adequate lesion expansion.
Lipoprotein(a) in restenosis after percutaneous transluminal coronary angioplasty and coronary artery disease.
Authors: Cooke T , Sheahan R , Foley D , Reilly M , D'Arcy G , Jauch W , Gibney M , Gearty G , Crean P , Walsh M
Published: June 2012

BACKGROUND

The purpose of the study was to investigate the relation of lipoprotein(a) and serum lipid parameters to restenosis after percutaneous transluminal coronary angioplasty (PTCA) and to assess the association of these same biochemical markers to coronary artery disease (CAD) in individuals with angiographically defined normal and diseased coronary arteries.

METHODS AND RESULTS

Sixty-two patients with successful PTCA had follow-up angiography at 35 +/- 10 weeks. Restenosis occurred in 21 male patients (46%) and 6 female patients (38%). Elevated apolipoprotein B (P < .01) and decreased high-density lipoprotein-2 cholesterol (P < .02) were found to be independently associated with restenosis after angioplasty, whereas lipoprotein(a) was not. Eighty-five patients undergoing PTCA were compared with 46 subjects who had no evidence of CAD on angiography. Elevated lipoprotein(a) (P < .001) and reduced apolipoprotein A1 to B ratio (P < .001) were found to be strong independent risk factors for the presence of CAD when adjustment was made for age (P < .005), male sex (P < .01), smoking (P < .005), and hypertension (P = .06).

CONCLUSIONS

Serum lipoprotein(a) levels are not associated with restenosis after PTCA, but elevated levels are strongly associated with CAD. Low-serum, high-density lipoprotein-2 cholesterol concentration and elevated apolipoprotein B concentration were found to be associated with restenosis after PTCA.
Effects of cardiac transplantation on bioenergetic abnormalities of skeletal muscle in congestive heart failure.
Authors: Stratton J R , Kemp G J , Daly R C , Yacoub M , Rajagopalan B
Published: June 2012

BACKGROUND

Patients with advanced heart failure have bioenergetic abnormalities of skeletal muscle metabolism during exercise. Using 31P magnetic resonance spectroscopy, we sought to determine whether skeletal metabolic responses to exercise are normalized by orthotopic cardiac transplantation.

METHODS AND RESULTS

Four groups were studied: healthy normal volunteers (n = 9), subjects awaiting heart transplantation (n = 10), subjects < 6 months (mean, 4 months) after transplant (n = 9), and subjects > 6 months (mean, 15 months) after transplant (n = 8). None of the posttransplant patients had biopsy evidence of rejection at the time of study. There were no significant differences in age, preoperative functional class, or symptom duration among the three patient groups. Metabolic responses were monitored in the dominant arm during incremental weight pull exercise and 10 minutes of recovery by 31P magnetic resonance spectroscopy, with measurement of pH and the phosphocreatine (PCr)/(PCr + inorganic phosphate [Pi]) ratio, an index of PCr concentration. In addition, based on recovery data, the rate of PCr resynthesis was calculated as a measure of oxidative metabolism that is independent of work level, recruitment, or muscle mass, and the effective maximal rate of mitochondrial ATP synthesis (Vmax) was determined. Analysis was by ANOVA. There were no differences between groups in pH or PCr/(PCr + Pi) at rest. Compared with the normal control group, the pretransplant group had a decreased exercise duration (11.3 +/- 2.5 versus 15.0 +/- 1.3 minutes, P = .02), a lower submaximal exercise PCr/(PCr + Pi) ratio (0.58 +/- 0.11 versus 0.76 +/- 0.08, P < .05), a reduced PCr resynthesis rate (13 +/- 6 versus 22 +/- 9 mmol/L per minute, P < .05), and a lower calculated Vmax (26 +/- 14 versus 53 +/- 26 mmol/L per minute, P < .05). In the group studied early after transplantation, all the changes noted in the pretransplant group persisted and were if anything somewhat worse. In the group studied late after transplantation, there was a significant improvement in the PCr resynthesis rate compared with the early-posttransplant group (27 +/- 6 late versus 15 +/- 6 mmol/L per minute early, P < .05) and statistically nonsignificant trends toward improvements in submaximal exercise pH (6.86 +/- 0.24 late versus 6.72 +/- 0.24 early) and submaximal PCr/(PCr + Pi) ratio (0.56 +/- 0.14 late versus 0.44 +/- 0.15 early) and Vmax (45 +/- 21 late versus 33 +/- 15 mmol/L per minute early). However, compared with normal subjects, exercise duration and submaximal PCr/(PCr + Pi) were still reduced in the late-posttransplant group.

CONCLUSIONS

Despite successful heart transplantation, skeletal muscle abnormalities of advanced heart failure persist for indefinite periods, although partial improvement occurred at late times. The persistent abnormalities may contribute to the reduced exercise capacity that is present in most patients after transplantation.
Survival in primary pulmonary hypertension. Validation of a prognostic equation.
Authors: Sandoval J , Bauerle O , Palomar A , Gómez A , Martínez-Guerra M L , Beltrán M , Guerrero M L
Published: June 2012

BACKGROUND

The prognosis of patients with primary pulmonary hypertension (PPH) remains a major problem for the planning and assessment of therapeutic interventions. The objectives of this study were (1) to characterize mortality in a Mexican population of patients with PPH and to investigate factors associated with survival and (2) to test the applicability in this population of the prognostic equation proposed by the US National Institutes of Health study on PPH.

METHODS AND RESULTS

A dynamic cohort of patients with PPH at our institution were enrolled between June 1977 and August 1991 and prospectively followed at regular intervals through September 1992. Measurements at diagnosis included hemodynamic and pulmonary function variables in addition to information on demographic data and medical history. The response to vasodilator treatment was also analyzed. The estimated median survival of the group was 4.04 years (95% confidence interval, 2.98 to 5.08 years). Variables associated with poor survival (univariate analysis) included an elevated mean right atrial pressure, a decreased cardiac index, and a decreased mixed venous PO2. A reduced forced vital capacity and the absence of vasodilator treatment were also associated with poor survival. A multivariate Cox proportional-hazards regression analysis was used to assess the adjusted hazard ratios, hence the relative contributions of the variables controlling for confounding. Reduced forced vital capacity and cardiac index and increased right atrial pressure were still significantly associated as risk factors for survival in patients with PPH. Survival as computed by the equation correlated with real survival of PPH patients with positive predictive values of 87%, 91%, and 89% at 1, 2, and 3 years, respectively. The equation, however, was relatively unable to predict deaths in our population, in part because of the strict limits of poor prognosis.

CONCLUSIONS

Mortality in PPH is largely associated with hemodynamic variables that assess right ventricular function. The proposed prognostic equation had a high sensitivity and a relatively low specificity to predict survival in our PPH population. To improve this specificity it may be necessary to increase the limits of poor prognosis as defined by the equation.
Arterial reactivity is significantly impaired in normotensive young adults after successful repair of aortic coarctation in childhood.
Authors: Gardiner H M , Celermajer D S , Sorensen K E , Georgakopoulos D , Robinson J , Thomas O , Deanfield J E
Published: June 2012

BACKGROUND

Despite successful repair of coarctation of the aorta in childhood, adult survivors often have hypertension at rest or on exercise, and their life expectancy is shorter than normal because of premature coronary and cerebrovascular disease. This may be related to persistent structural and functional arterial abnormalities after surgery.

METHODS AND RESULTS

Using high-resolution ultrasound, we studied the right brachial arteries of 25 normotensive young adults who had undergone successful repair of coarctation in childhood (mean age at repair, 62 months; range, 0 to 167 months, including 8 patients operated on in infancy; mean age at study, 19 years; range, 14 to 27 years) and 50 age- and sex-matched control subjects. We assessed the degree of reactive hyperemia (RH) produced after distal cuff occlusion and release and the changes in arterial diameter in response to RH (with increased flow causing endothelium-dependent dilation) and to glyceryltrinitrate (GTN, an endothelium-independent dilator). The response of the right femoral artery to GTN was also measured in 12 coarctation subjects and 12 control subjects. Studies were performed 13.7 years (range, 7 to 21 years) after surgery. RH was significantly lower in coarctation subjects (343 +/- 130% versus 482 +/- 147%), as were endothelium-dependent dilation (3.8 +/- 3.3% versus 8.8 +/- 3.6%) and GTN response (13.3 +/- 6.0% versus 20.5 +/- 6.1%) (P < .001 for each), reflecting abnormal dilatory capacity in both the resistance and conduit arteries. In contrast, GTN-induced dilation in the femoral arteries was similar to that in control subjects (9.5 +/- 2.6% versus 10.1 +/- 4.1%, P = .70). On multivariate analysis, GTN response and systolic blood pressure at peak exercise were inversely correlated (r = -.52, P = .04). Vascular responses were not related to the age at repair.

CONCLUSIONS

Despite successful repair of coarctation in childhood, arterial dilation is significantly impaired in the precoarctation vascular bed of healthy young adults. This may be an important contributor to exercise-related hypertension and late morbidity or mortality.
Intracoronary versus intravenous effects of cocaine on coronary flow and ventricular function.
Authors: Zimring H J , Fitzgerald R L , Engler R L , Ito B R
Published: June 2012

BACKGROUND

Cocaine use has been associated with cardiomyopathy and ischemic coronary syndromes. However, the pathophysiological mechanisms responsible for these syndromes are not clear and have been suggested to involve direct effects of cocaine on myocyte contractility and coronary resistance as well as indirect effects via altered autonomic tone, secondary mediators, and myocardial metabolism. We sought to distinguish direct from indirect effects of cocaine on ventricular function and coronary resistance by comparison of the administration of intracoronary cocaine (0.12 to 0.36 mg/min constant infusion) with intravenous cocaine (5 mg/kg bolus infusion) in an in vivo anesthetized pig preparation.

METHODS AND RESULTS

To control for changes in coronary resistance secondary to autoregulation and myocardial metabolism, the left anterior descending coronary artery was perfused at constant coronary pressure and the interventricular vein was cannulated for coronary venous oxygen saturation measurement. Coronary blood flow, regional percent segment shortening, myocardial oxygen consumption, and serum cocaine concentrations were measured. Intracoronary cocaine produced a dose-dependent decrease in percent segment shortening in the absence of significant changes in coronary flow or systemic hemodynamics. In contrast, intravenous cocaine had mild biphasic effects on coronary resistance with an initial brief vasodilation (30.0 +/- 5% increase in flow from control) followed by more prolonged vasoconstriction (17.0 +/- 3.3% decrease in flow from control), which were independent of autoregulation or myocardial metabolism. In addition, intravenous cocaine caused an early 48% decrease in percent segment shortening, at which time the measured cocaine concentration was 20.1 micrograms/mL blood. This was comparable to the intracoronary cocaine concentration of 17.1 micrograms/mL blood, which produced a similar 48% decrease in percent segment shortening.

CONCLUSIONS

We conclude that the effects of acute cocaine exposure on ventricular function are predominantly direct but of brief duration and therefore probably not clinically relevant. The effects of cocaine on coronary tone are predominantly indirect and biphasic, with early vasodilation followed by mild and more prolonged vasoconstriction. In the absence of coronary stenosis or ventricular hypertrophy, this small amount of vasoconstriction is unlikely to cause ischemia.
Role of endothelium in the maintenance of low pulmonary vascular tone in normal children.
Authors: Celermajer D S , Dollery C , Burch M , Deanfield J E
Published: June 2012

BACKGROUND

Resting vascular tone is low in the normal pulmonary circulation, and experimental studies have suggested that this may be due to the continuous release of endothelium-derived nitric oxide (NO), a locally acting vasodilator. We have investigated whether NO contributes to the normal control of pulmonary vascular tone and resistance in children.

METHODS AND RESULTS

We studied the hemodynamic effects of NG-monomethyl-L-arginine (L-NMMA), a specific inhibitor of NO synthesis, on the pulmonary circulation of six children 2 to 17 years old (mean, 9 years) with congenital heart disease but normal pulmonary blood flow, pressure, and resistance (all had isolated left heart obstructive lesions). The diameter of a segmental pulmonary artery and pulmonary blood flow velocity were measured by quantitative angiography and intra-arterial Doppler catheters. There was a consistent, dose-dependent fall in pulmonary blood flow velocity in response to three increasing doses of L-NMMA (compared with baseline, flow velocity fell to 75 +/- 7%, 62 +/- 8%, and 40 +/- 10%, P < .01). Flow velocity returned to control values with subsequent infusion of L-arginine, the substrate for NO. Thereafter, acetylcholine, an endothelium-dependent dilator, produced an increase in flow velocity (56 +/- 10% greater than baseline, P < .01). Arterial diameter was unchanged during L-NMMA and L-arginine infusions, indicating that the major effect of each agent is to alter vascular tone distal to the segmental pulmonary arteries.

CONCLUSIONS

The dilator action of endothelium-derived NO contributes to the maintenance of low resting pulmonary tone in normal children. Impairment of NO production may contribute to the elevated pulmonary vascular resistance that complicates some cases of congenital heart disease.
Dynamic nature of the aortic regurgitant orifice area during diastole in patients with chronic aortic regurgitation.
Authors: Reimold S C , Maier S E , Fleischmann K E , Khatri M , Piwnica-Worms D , Kikinis R , Lee R T
Published: June 2012

BACKGROUND

The effective aortic regurgitant orifice area varies with aortic pressure in animal models of acute aortic regurgitation. The purpose of this study was to determine whether the aortic regurgitant orifice area changes during diastole in patients with chronic aortic regurgitation.

METHODS AND RESULTS

Two-dimensional and Doppler echocardiography were performed immediately before and after magnetic resonance velocity mapping using a cine phase contrast sequence in 17 patients with chronic aortic regurgitation. ECG-gated continuous-wave Doppler velocity time integrals and magnetic resonance flow rates were measured 16 times per cardiac cycle. The mean aortic regurgitant orifice area (centimeters squared) was calculated by the continuity equation. The regurgitant orifice area was also determined for each diastolic acquisition interval. Changes in the regurgitant orifice area during diastole were modeled using an asymptotic exponential decay model to determine the static and dynamic components of the orifice. The regurgitant orifice area increased directly with regurgitant fraction (y[cm2] = 0.0072[cm2/%]*x[%]-0.0409[cm2]; r = .86, P < .0001). In 15 of 17 (88%) patients, the regurgitant orifice area decreased during diastole. The dynamic component of the regurgitant orifice area decreased with increasing regurgitant fraction (y[%] = -0.98x[%]+96.9[%]; r = -.90, P < .0001). There were no significant differences in heart rate, systolic or diastolic blood pressures, or continuous-wave Doppler velocity time integrals measured before or after the magnetic resonance examination.

CONCLUSIONS

The effective regurgitant orifice area decreases during diastole in patients with chronic aortic regurgitation. This phenomenon should be considered when evaluating aortic regurgitant severity.