HIGHLIGHTS FROM JACC IN 2003
Highlights of the year in JACC 2003
Anthony N. DeMaria, MD*,*,
Ori Ben-Yehuda, MD*,
Daniel Berman, MD ,
Gregory K. Feld, MD*,
Barry H. Greenberg, MD*,
James D. Knoke, PhD*,
Kirk U. Knowlton, MD*,
Wilbur Y. W. Lew, MD* and
Sotirios Tsimikas, MD*
* From the Cardiology Division, University of California-San Diego Medical Center, San Diego, California, USA.
Cedars-Sinai Medical Center, Los Angeles, California, USA.
Manuscript received October 21, 2003;
accepted October 23, 2003.
* Reprint requests and correspondence: Dr. Anthony N. DeMaria, Cardiology Division, UCSD Medical Center, 200 West Arbor Drive, San Diego, California 92103-8411, USA
ademaria{at}ucsd.edu
This month, in lieu of an Editor's Page, the editors of JACC introduce a new feature that will occur annually. The editors have each summarized articles published in JACC that are of particular significance clinically or with regard to research. These papers represent the highlights of the past 12 months in JACC, as selected by the editors. We believe that these manuscripts represent important emerging areas in cardiology and point to additional developments we will see in the future.
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Coronary artery disease/acute myocardial infarction
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Three themes emerged in reports addressing coronary artery disease (CAD) and myocardial infarction (MI) in the pages of the Journal over the past year: 1) the role of inflammation and the value of C-reactive protein (CRP); 2) the refinement of risk assessment both in chronic and acute coronary disease; and 3) the improvement of current therapy, both validating new pharmacologic approaches and implementing proven therapies.
Inflammation.
Inflammation has now been recognized as playing a central role in atherosclerosis and endothelial dysfunction. Emerging evidence points to CRP not only as a marker of disease, but also playing a causal role in endothelial dysfunction and atherogenesis. A study by Cosin-Sales et al. (1) extended the role of CRP as a marker of CAD to patients with chest pain and normal coronary angiograms. Although some of these patients have non-cardiac causes of chest pain, endothelial dysfunction may play an important role in the pathogenesis of syndrome X. Cosin-Sales et al. (1) reported on 137 patients with chest pain and normal coronary angiograms. High-sensitivity C-reactive protein (hs-CRP) levels were higher in patients with frequent and prolonged chest pain episodes, as well as in those with ST-segment depression on Holter monitoring and exercise testing. Moreover, hs-CRP was the only independent variable predictive of positive Holter and exercise test findings. Thus, hs-CRP may assist in the diagnosis of syndrome X patients and further substantiates the role of inflammation in this entity.
Biomarkers.
The field of biomarkers continues to evolve rapidly, with new data not only on acute coronary syndrome but also on other cardiovascular diseases. A study by Landesberg et al. (2) illustrated the power of newer generation troponin assays and creatine kinase-MB isoenzyme to risk-stratify patients undergoing major vascular surgery. In a cohort of 447 consecutive patients, they found that even minor elevations of troponin and creatine kinase-MB isoenzyme were potent risk predictors. Patients having elevations in one marker had a two- to three-fold risk of mortality. Patients with elevation of both markers had a 4.19-fold increase in long-term mortality. Most importantly, although 24% of patients had elevations in biomarkers, only 3.6% presented with symptoms and only 5.6% met previous World Health Organization criteria for MI.
Renal insufficiency.
The effect of renal insufficiency on cardiovascular risk was the subject of numerous articles, increasing our awareness of the importance of renal dysfunction in cardiology. In a retrospective study utilizing data from the Thrombolysis In Myocardial Infarction (TIMI)-10, TIMI-14, and Intravenous nPA for Treatment of Infarcting Myocardium Early (InTIME)-2 trials, Gibson et al. (3) demonstrated that 30-day mortality in ST-segment elevation myocardial infarction (STEMI) patients increased stepwise with increasing creatinine levels and impaired creatinine clearance, independent of other conventional risk factors and the TIMI risk score. An independent contribution of renal dysfunction, after controlling for CRP and the extent of CAD, was also found in a study by Zebrack et al. (4) of patients without MI. In their study of 1,484 patients who underwent angiography and were followed for a mean of three years, renal insufficiency was associated with unadjusted hazard ratios of 2.3 for death/MI and 5.4 for renal failure. Adjustment for CRP, CAD score, and all other risk factors had a minimal or modest impact on the risk, indicating that renal insufficiency is an independent predictor. Although the underlying mechanism of this increased risk is uncertain, clinicians will need greater awareness of renal dysfunction in the assessment of the cardiac patient. Indeed, in a related report, Berger et al. (5), using the End-Stage Renal Disease and Cooperative Cardiovascular Project databases, documented that patients with end-stage renal disease were less likely to be treated with aspirin, beta-blockers, and angiotensin-converting enzyme inhibitors during admission for acute MI, yet the benefit of these simple interventions appeared to be maintained compared with patients without end-stage renal disease.
Pharmacologic therapy of acute MI.
The search for new therapies in MI continue to generate intense study. With the advent of glycoprotein (GP) IIb/IIIa inhibitors and the recognition that platelets play a key role in MI, it was hoped that combination therapy with reduced-dose lytic and GP IIb/IIIa inhibition would improve reperfusion therapy. The Integrilin and Tenecteplase in Acute Myocardial Infarction (INTEGRITI) phase II angiographic trial (6) examined the role of eptifibatide in combination with different tenecteplase doses. Patients randomized to combination therapy tended to have more TIMI 3 flow grade, arterial patency, and ST-segment resolution, but also more major hemorrhage and transfusions. The investigators concluded that further study was necessary before this combination therapy could be recommended for general use.
Glucose-insulin-potassium, an "old" therapy advocated since the early 1960s, was the subject of a clinical trial, the largest such trial reported to date and the first in patients treated with primary percutaneous transluminal coronary angioplasty (7). When infused over 8 to 12 h, glucose-insulin-potassium was studied in an open-label trial of 940 patients undergoing percutaneous transluminal coronary angioplasty for STEMI. Overall, there was a trend toward a mortality reduction at 30 days: 4.8% in the glucose-insulin-potassium group versus 5.8% in the control group. In 856 patients without heart failure (HF) on presentation, there was a significant reduction in mortality from 4.2% to 1.2%. The lack of benefit in patients who presented with HF may be related to the large volume load given in the study. Although further studies are clearly needed, the results of this trial emphasized the potential of metabolic interventions to improve therapy in acute MI.
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Interventional cardiology
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Primary percutaneous coronary intervention (PCI) with adjunctive GP IIb/IIIa inhibitors.
The use of GP IIb/IIIa inhibitors in primary PCI is controversial. The trial reported by Antoniucci et al. (8) randomized 400 patients with acute STEMI to infarct-related artery stenting plus abciximab or stenting alone. The primary end point (composite of death, reinfarction, target vessel revascularization, and stroke at one month) was lower in the abciximab/stenting group compared with the stenting alone group (4.5% vs. 10.5%, p = 0.023). This was also associated with faster ST-segment resolution, improved left ventricular (LV) function at one month, and improved mortality at six months (5.5% vs. 13.5%, p = 0.006). Bleeding complications were similar among groups.
As Topol et al. (9) point out in an accompanying editorial, pooling the data from this trial and four previous trials addressing this issue (RePro in Acute myocardial infarction and Primary PTCA Organization and Randomized Trial [RAPPORT], Intracoronary Stenting and Antithrombotic Regimen [ISAR]-2, Abciximab before Direct Angioplasty and stenting in Myocardial Infarction Regarding Acute and Long-term followup [ADMIRAL], and Controlled Abciximab and Device Investigation to Lower Late Angioplasty Complications [CADILLAC]) resulted in an overall 46% reduction in death, reinfarction, and target vessel revascularization, a 34% reduction in death or reinfarction, and a 26% reduction in death, providing strong and consistent evidence of a benefit for adjunctive use of abciximab with catheter-based reperfusion for MI.
Daytime versus nighttime primary PCI.
It is unclear whether the benefits of PCI are comparable for nighttime and daytime. Henriques et al. (10) evaluated the impact of circadian patterns in the onset and treatment of STEMI on the outcomes of primary angioplasty in 1,702 consecutive patients. They observed circadian variation in frequency of symptom onset, hospital admission, and first balloon inflation, with the majority of patients ( 52%) presenting and having PCI during routine duty hours. There were no differences in baseline clinical characteristics or treatment delays between patients treated during routine duty hours (8 AM to 6 PM) and off-hours (6 PM to 8 AM). However, daytime hospital admission was associated with a lower angioplasty failure rate (3.8% vs. 6.9%, p < 0.01) and 30-day mortality (1.9% vs. 4.2%, p < 0.01), compared with nighttime hospital admission. The authors postulated several explanations for these findings, including different patient characteristics, improved care during the daytime, and possibly increased resistance of fibrinolyis and prothrombotic tendencies in the evening due to circadian mechanisms. This intriguing observation was editorialized by Spencer and Becker (11), who suggested that much of this effect may be due to baseline patient characteristics (i.e., patients with HF may present in a circadian pattern and more often in the evening), differences in health-seeking behavior or health care delivery, and physician availability. With the increasing use of primary PCI, these findings warrant further research, as the public health impact is very significant.
Facilitated PCI.
Recent studies have shown a superiority of primary stenting over thrombolytics in STEMI patients. However, it was uncertain whether rapid transfer to a PCI-capable hospital was beneficial to patients arriving at a hospital without PCI facilities. The Streptokinase in Acute Myocardial Infarction (SIAM III) study by Scheller at al. (12), was a multicenter, randomized, prospective, controlled trial including 163 patients receiving thrombolysis during STEMI. One cohort was transferred within 6 h after thrombolysis for catheterization and PCI, whereas the other group received elective coronary angiography at two weeks after initial thrombolysis and, if indicated, stenting of the infarct-related artery. Immediate stenting after thrombolysis was associated with a significant reduction in the combined end point after six months (ischemic events, death, reinfarction, target lesion revascularization; 25.6% vs. 50.6%, p = 0.001), despite a 23% crossover in the thrombolysis only group. There was an improvement in LV function at six months. However, there was an 8.6% risk of major bleeding and a 2.4% incidence of stroke. No difference in mortality was noted, but the trial was not powered for this end point. This trial complements the findings of previous trials, such as DANish trial in Acute Myocardial Infarction (DANAMI-2), PRimary Angioplasty in patients transferred from General community hospitals to specialized PTCA Units with or without Emergency thrombolysis (PRAGUE), and AIR-PAMI, showing improved outcomes in patients transferred to a specialized center for facilitated PCI. As McKay (13) points out in an accompanying editorial, only 25% of hospitals in the U.S. and 10% in Europe can offer PCI, and there is often a significant time delay in transferring patients for PCI. Although this study has the limitations of a prolonged delay in reperfusion and a substantial bleeding risk and is underpowered for hard events, the approach of facilitated PCI is viable but requires additional studies "to end the long-standing debate about the relative superiority of pharmacologic over mechanical intervention, so that we can move forward in an attempt to find an even better reperfusion option."
Do GP IIb/IIIa inhibitors prevent mortality?.
Although GP IIb/IIIa inhibitors reduce post-PCI cardiac enzyme elevations, previous studies were not powered to show a benefit in overall mortality. In a meta-analysis of all PCI trials using GP IIb/IIIa inhibitors, including over 20,000 patients, Karvouni et al. (14) showed that GP IIb/IIIa inhibitors decreased the risk of death at 30 days and up to 1 year (21% relative risk reduction, p = 0.008). This risk reduction was independent of clinical presentation, PCI approach (stent vs. balloon), or use of postprocedural heparin. Major bleeding was significantly increased only in trials where heparin was continued after the procedure. Although this study has all the limitations of a meta-analysis, it does suggest that GP IIb/IIIa inhibitors may have a beneficial effect on mortality in PCI.
Treatment of in-stent restenosis (ISR).
Balloon angioplasty versus repeat stenting for ISR
Coronary brachytherapy is not widely available worldwide to treat all patients with ISR (estimated at 150,000 per year in the U.S.) and has certain regulatory and technical limitations. To evaluate alternative strategies to treat ISR, Alfonso et al. (15) performed the first randomized clinical trial comparing repeat stenting with conventional balloon angioplasty in patients with ISR. They randomly assigned ISR patients to stent implantation (n = 224) or conventional balloon angioplasty (n = 226). The primary end point—recurrent restenosis rate at six months—was similar (38% to 39%), as was one-year event free survival, despite a larger postprocedural minimum lumen diameter in the stenting group (2.77 vs. 2.25 mm, p < 0.001). Prespecified subgroup analyses in large vessels (>3 mm) showed a reduced restenosis rate (27% vs. 49%, p = 0.007) and improved event-free survival (84% vs. 62%, p = 0.002) in the repeat stenting group, largely due to a reduced need for repeat interventions. The authors conclude that in patients with ISR, repeat coronary stenting provides better initial angiographic results but failed to improve the restenosis rate and clinical outcome, as compared with conventional balloon angioplasty. However, in patients with large vessels, coronary stenting improved the long-term clinical and angiographic outcome.
Conventional balloon angioplasty versus cutting balloon angioplasty for ISR
To compare cutting balloon angioplasty with conventional balloon angioplasty, Albiero et al. (16) reported the REStenosis CUtting balloon evaluation Trial (RESCUT), a multicenter, randomized, prospective study that enrolled 428 patients with all types of ISR (focal, multifocal, diffuse, or proliferative). At seven-month follow-up, there was no difference between the groups in angiographic binary restenosis rate (cutting balloon angioplasty 29.8%; conventional balloon angioplasty 31.4%), pattern of recurrent restenosis, and clinical events. However, cutting balloon angioplasty was associated with some procedural advantages over conventional balloon angioplasty, such as use of fewer balloons, less requirement of additional stenting, and lower incidence of balloon slippage.
Sirolimus-eluting stents for ISR
This small observational study from the Thoraxcenter by Degertekin et al. (17) reports the first human experience with drug-eluting stents for ISR. One or more sirolimus-eluting stents were implanted in 16 patients with severe, recurrent ISR in a native coronary artery and with objective evidence of ischemia. Quantitative angiographic and three-dimensional intravascular ultrasound follow-up performed at four months showed four patients (25%) with recurrent restenosis. Clinical follow-up at nine months revealed that three patients had experienced four major adverse cardiac events (two deaths and one acute MI necessitating repeat target vessel angioplasty).
These studies on the treatment of ISR show that repeat stenting and cutting balloon angioplasty for ISR do not lead to an overall reduction in dichotomous angiographic restenosis or major adverse cardiac events; therefore, their use will find niche applications such as balloon slippage, inadequate angiographic results, or restenosis in very large vessels. Pending further studies, coronary brachytherapy appears to be the best initial modality for the initial episode of ISR, although the jury is out for recurrent ISR.
Appropriate hospital volumes for PCI.
Significant debate has taken place over the past decade regarding the appropriate volumes of PCI for both interventional cardiologists and hospitals. The American College of Cardiology (ACC)/American Heart Association (AHA)-proposed guidelines recommend a minimum of 400 procedures for hospitals that offer PCI. Krumholz et al. (18) conducted a retrospective analysis of the Agency for Healthcare Research and Quality nationwide inpatient sample hospital discharge database to evaluate in-hospital mortality among patients (n = 362,748) who underwent PCI between 1998 and 2000 at low (5 to 199 cases/year), medium (200 to 399 cases/year), high (400 to 999 cases/year), and very high ( 1,000 cases/year) PCI-volume hospitals.
An inverse association was found between hospital PCI volume and in-hospital mortality (2.56%, 1.83%, 1.64%, and 1.36% at low-, medium-, high-, and very-high-volume hospitals, respectively; p < 0.001 for trend). After multivariate adjustment, patients at low-volume hospitals remained at increased risk (odds ratio 1.21, 95% confidence interval 1.06 to 1.28), whereas patients at medium- and very-high-volume hospitals had a comparable mortality risk. The study lacked angiographic information to relate to procedural risk, data on whether low-volume hospitals referred high-risk cases to high-volume centers, and data on the outcomes of individual physicians. The authors suggest a re-evaluation of the ACC/AHA guidelines regarding the minimum standards required for hospitals performing PCI, which will have major implications on the number of hospitals able to provide PCI to their patients.
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Noninvasive cardiology
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Strain rate and backscatter imaging in diabetes.
Although abnormalities in contractile performance have been recorded in asymptomatic diabetics, the potential contribution of co-existing hypertension or CAD to these findings remains uncertain. Therefore, Fang et al. (19) studied 186 patients with a normal ejection fraction and no evidence of CAD: 48 patients with diabetes only, 45 patients with LV hypertrophy only, 45 patients with both diabetes and LV hypertrophy, and 48 normal controls. Measurements of peak strain and strain rate derived from Doppler tissue imaging demonstrated impaired systolic function compared with controls in all groups; values were lowest in the group with both diabetes and hypertrophy. Integrated backscatter imaging revealed increased intensity levels in all patient groups compared with controls. Thus, this study documented the existence of impaired myocardial performance in diabetics, even in the absence of hypertension/hypertrophy and coronary disease. Moreover, it demonstrated the sensitivity of strain rate imaging in detecting abnormal myocardial performance, even in the setting of normal LV structure and ejection fraction.
Flow-mediated brachial artery dilation.
It is now recognized that coronary atherosclerosis is very prevalent in patients with peripheral vascular disease and is likely to result in adverse events either with surgical interventions or during long-term follow-up. To further identify patients with peripheral vascular disease at risk of coronary events, Gokce et al. (20) assessed endothelial function by measuring changes in flow-mediated brachial artery diameter by ultrasound in approximately 200 patients with peripheral artery disease scheduled for vascular surgery. This study demonstrated that endothelium-dependent flow-mediated dilation was significantly lower in the 35 of 199 patients who experienced an event over a 15-month follow-up than in those who did not (4.4% vs. 7.0%, p < 0.001). In fact, abnormal endothelial function was one of three independent risk factors in addition to older age and more invasive surgery for cardiac events. Thus, this study established that impaired endothelial function, as delineated by ultrasound measurements of brachial artery diameter, identified patients with peripheral vascular disease who were at risk of a coronary event and who might benefit by more intensive management.
Integrated backscatter analysis in muscular dystrophy.
Although congestive HF is common in the late stages of Duchenne's muscular dystrophy, the onset of myocardial abnormalities in this entity remains uncertain. Therefore, Giglio et al. (21) assessed integrated myocardial backscatter by means of acoustic densitometry in 20 patients with Duchenne's muscular dystrophy compared with age-matched normal subjects. They observed that cyclic variation of integrated backscatter was reduced in the muscular dystrophy patients (4.4 vs. 8.8 dB), whereas total integrated backscatter values were increased. These data demonstrate that myocardial abnormalities occur early in the course of Duchenne's muscular dystrophy and antedate any evidence of impaired LV ejection fraction. The study provides important evidence of the ability of acoustic integrated backscatter analysis to detect subclinical abnormalities of the myocardium. As pointed out by Towbin (22) in an accompanying editorial, since all patients with dystrophin deficiency are at risk for the development of dilated cardiomyopathy (DCM), they are candidates to be screened by this type of noninvasive technique. Moreover, ultrasonic findings could conceivably provide an end point for assessing the value of drug therapy in these patients.
Echocardiographic findings after mediastinal irradiation.
Although a variety of cardiovascular complications are known to follow mediastinal irradiation, particularly when administered for Hodgkin's disease, the prevalence and nature of cardiac abnormalities in asymptomatic patients after irradiation is unknown. Heidenreich et al. (23) studied this question by performing standard transthoracic echocardiography in 294 asymptomatic patients, many of whom had received mediastinal irradiation for Hodgkin's disease over 20 years before evaluation. Compared with patients who had been irradiated <10 years earlier, patients treated >20 years earlier had a greater incidence of aortic regurgitation (62% vs. 4%), moderate or greater mitral regurgitation (6% vs. 2%), and aortic stenosis (16% vs. 0%). Moreover, in comparison to a control population from the Framingham Heart Study, more patients manifested reduced LV shortening, and the group exhibited a lower LV mass. These data demonstrate that cardiac abnormalities are very prevalent in asymptomatic patients who have received at least 35 Gy of mantle radiation, and that such abnormalities are more common over time. As pointed out in an accompanying editorial by Byrd (24), the valvular regurgitation and reduced LV function and mass observed in this study raise the question as to whether treatment with prophylactic antibiotics and angiotensin-converting enzyme inhibitors should be attempted in these patients. Despite the assumed resistance of cardiac structures to radiation therapy, this report documents that newer methods of irradiation are necessary to protect the heart and great vessels.
Left atrial appendage obliteration to reduce thromboembolism.
The potential benefit of left atrial obliteration in patients with atrial fibrillation (AF) who have contraindications to warfarin remains controversial. In the past year, two studies addressed this problem. Garcia-Fernandez et al. (25) evaluated the value of ligation of the left atrial appendage in patients undergoing mitral valve replacement/repair. The left atrial appendage was ligated in 58 of 205 patients. During a median time from surgery of 69 months, 27 patients had an embolic event for which the absence of left atrial appendage ligation or the presence of left atrial thrombus was the only independent predictor. Furthermore, when the absence of left atrial appendage ligation was considered in combination with evidence of incomplete closure identified by transesophageal echocardiography, the risk of embolism increased approximately 12 times. These data attest to the role of the left atrial appendage in systemic embolization, the value of ligation, and the role of transesophageal echocardiography in detecting incomplete closure. In patients with AF who are not candidates for warfarin therapy, a new thorascopic approach to obliteration of the left atrial appendage was described by Blackshear et al. (26). Using either a loop snare or stapler, these investigators obliterated the left atrial appendage without thoracotomy in 14 of 15 patients. Two strokes were observed in these patients after a mean follow-up of 42 months. Thus, this thorascopic approach warrants further evaluation as an alternative therapy to reduce thromboembolism in AF patients in whom warfarin is contraindicated. As pointed out in an accompanying editorial by Halperin (27), patients with AF often have many potential sources of systemic emboli. These studies provide evidence that left atrial appendage remains a likely cause for emboli in such patients, and that a variety of interventions may be of value in preventing these events.
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Heart failure/heart transplantation
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Implementation of clinical trial results.
The Randomized ALdactone Evaluation Study (RALES) (28) showed that adding spironolactone to standard therapy could improve survival in some HF patients. To determine how the results of RALES were being translated into clinical practice, Bozkurt et al. (29) evaluated spironolactone use at a large VA Hospital immediately after release of the RALES results. They found that spironolactone was initiated in many patients who had less severe HF or more severe renal dysfunction than did the patients in RALES, and that follow-up measurements of serum potassium levels were less frequent in practice than in the trial. Furthermore, patients at their hospital experienced a considerably higher incidence of hyperkalemia than did the patients in RALES. These results imply that patients with less severe HF (who might not derive as much benefit as the RALES population) were exposed to the same (or greater, in the case of renal dysfunction patients) risk as RALES patients, and that the potentially serious adverse effects of spironolactone therapy were not given as much attention as the beneficial ones. In an accompanying editorial, Tang and Francis (30) commented that the trial results from a carefully defined population may be inappropriately translated into the general population, and that problems remain in disseminating information from clinical trials to practicing physicians.
Post-transplant hypertension.
Hypertension is a frequent and often difficult-to-treat problem after heart transplantation. Although a number of factors probably contribute to the development of this condition, the mechanism(s) involved are poorly understood. In an elegant study, Braith et al. (31) found that the diuretic and natriuretic response to a volume load is blunted in transplant recipients due to an inability to suppress the activity of the renin-angiotensin-aldosterone system. As noted in the accompanying editorial by Eisen (32), these results imply that the use of angiotensin-converting enzyme inhibitors and salt restriction should be particularly effective in treating hypertension after heart transplantation.
Post-infarct remodeling.
Post-MI LV remodeling adversely affects cardiac function and is recognized as a major cause of HF. The role of cardiac myocyte apoptosis in the development of structural changes and HF during post-MI remodeling was assessed by Abbate et al. (33) in a postmortem study of the hearts of 14 patients who died late after acute MI. The investigators found that the rate of apoptosis at both the infarct site and in noninfarcted segments of myocardium correlated significantly with measures of unfavorable LV remodeling. As noted by Mani and Kitsis (34), this report suggests that continued apoptosis of cardiac myocytes may play an important role in post-MI remodeling and the transition to HF. These results imply that anti-apoptotic therapies may prove useful in preventing HF, and this report will help provide a baseline for future studies in this area.
Beta-blocker therapy.
Although beta-blocking agents have now been established as standard therapy for HF due to systolic dysfunction, the value of this approach for HF complicated by renal dysfunction requiring dialysis is unknown. Cice et al. (35) reported the results of a placebo-controlled trial of carvedilol treatment in 114 patients with DCM on dialysis. They found that carvedilol was associated with significant attenuation of pathologic LV remodeling, and that there were significantly fewer deaths and hospitalizations in patients receiving active drug compared with placebo. These results provide a rationale for the initiation of carvedilol therapy in HF patients requiring dialysis.
Nutrition and HF.
Reduced physical activity is characteristic of patients with HF. To determine whether inadequate nutrition might contribute to this important problem, Aquilani et al. (36) assessed the nutritional intake in lean patients with HF compared with matched controls. From a seven-day diary, they found that the HF patients had a negative caloric and nitrogen balance compared with controls, and that energy availability in HF patients was significantly lower. Thus, HF patients may have reduced energy available for physical activities, and this may contribute to the exercise limitation seen in this condition. In an accompanying editorial, Silver (37) notes that although HF patients are given frequent advice about salt intake, little attention has been paid to the mechanisms responsible for and the clinical consequences of inadequate nutritional intake. Because poor nutrition, impaired absorption across the intestinal wall, and increased metabolic demands may all be present in HF patients (in particular, those patients with more advanced disease), greater attention to these issues is clearly warranted by clinicians and researchers alike.
Left lateral decubitus avoidance.
To assess whether avoidance of the left lateral decubitus position occurs in HF and to provide insight into the mechanisms responsible, Leung et al. (38) extensively studied a group of 75 HF patients and a comparable control group using nocturnal polysonography. Heart failure patients also underwent echocardiographic and right heart catheterization studies. Compared with control subjects, the HF patients spent significantly less time on their left side, which was accentuated in patients with a larger heart size and evidence of more severely compromised hemodynamic parameters. These results confirm that HF patients avoid lying on their left side and suggest that this preference is related to chest wall discomfort due to an increased heart size or further hemodynamic or autonomic compromise brought on by the left lateral decubitus position.
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Electrophysiologic disorders
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Risk stratification in asymptomatic Wolff-Parkinson-White (WPW) syndrome.
To risk-stratify patients with WPW syndrome, Manguso et al. (39) performed electrophysiologic studies in 212 consecutive asymptomatic patients with WPW syndrome, 162 of whom underwent a second electrophysiologic study at five years. At the electrophysiologic study, 115 patients had no inducible arrhythmia, whereas 47 patients were inducible. Of the 115 patients with no inducible arrhythmia, only 3.4% became symptomatic. Of the 47 patients who were inducible at the follow-up electrophysiologic study, 29 patients developed symptomatic arrhythmias, 8 of whom developed AF and 2 of whom experienced cardiac arrest. Those with symptoms or AF were younger and had a shorter accessory pathway refractory period and multiple accessory pathways. The authors concluded that in asymptomatic patients with WPW syndrome, electrophysiologic testing might be a valuable tool for identifying patients at risk of developing symptomatic arrhythmias and possibly sudden death. Thus, it may be warranted to perform electrophysiologic testing even in asymptomatic WPW patients and then to perform ablation to eliminate accessory pathway conduction in those at risk.
Pulmonary vein ablation for AF.
Pappone et al. (40) compared the clinical course of 589 patients who underwent pulmonary vein isolation using radiofrequency catheter ablation for AF with that of 582 patients who underwent medical therapy, from a total of 1,171 consecutive patients referred for treatment. After a median of 900 days of follow-up, Kaplan-Meier analysis showed a statistically significant advantage of pulmonary vein ablation over medical therapy for recurrence of AF, all-cause mortality, and morbidity due to congestive HF and ischemic cerebrovascular events. Quality-of-life assessment reached normal values at six-month follow-up and remained normal up to one year, in contrast to medically treated patients. Thus, this study raises the remarkable possibility that pulmonary vein ablation may not only cure AF, but may also improve quality of life and reduce morbidity and mortality. These findings suggest the need for a large, randomized trial of pulmonary vein ablation for atrial versus medical therapy.
Genetic model of cardiac hypertrophy and WPW syndrome.
Recent studies have demonstrated that several different missense mutations in PRKAG2, the gene for the two regulatory subunits of adenosine monophosphate-activated protein kinase, may cause cardiac disease characterized by conduction disorders and WPW syndrome, both with and without ventricular hypertrophy. Berul et al. (41) demonstrated in a transgenic mouse model that a clinical phenotype consistent with cardiac hypertrophy and pre-excitation syndrome (WPW) could be produced by overexpression of a mutant human gene. By week four after birth, seven of eight mice with mutant deoxyribonucleic acid (DNA) developed pre-excitation patterns on the electrocardiogram (ECG). Electrophysiologic testing revealed that mice expressing the mutant human gene, but not wild-type, had evidence of atrioventricular (AV) connections separate from the AV node. These accessory connections could be blocked by procainamide, whereas adenosine produced AV block in wild-type mice but not in those with mutant DNA and accessory connections. Histologic examination revealed evidence of a myocardial connection through the annulus fibrosum in mutant but not wild-type mice. Thus, although this study did not reveal the molecular mechanism by which mutant Asn488Ile human PRKAG2 complementary DNA resulted in the development of accessory AV connections similar to those observed in humans with the same mutation, it did establish a potentially useful model for studying such mechanisms in the future.
Microvolt T-wave alternans to predict ventricular tachyarrhythmia.
Hohnloser et al. (42) prospectively followed 137 patients with DCM for a period of 14 ± 6 months for three main end points: 1) sudden death, 2) resuscitated ventricular fibrillation, and 3) hemodynamically unstable ventricular tachycardia. Patients were risk-stratified for these end points during the follow-up using noninvasive tests, including: microvolt T-wave alternans, LV ejection fraction, baroreflex sensitivity, heart rate variability, presence of nonsustained ventricular tachycardia, signal-averaged ECG, and presence of intraventricular conduction defect. During follow-up, a total of 18 patients (13%) developed one of the prespecified study end points. Statistical analysis revealed that microvolt T-wave alternans and baroreflex sensitivity were univariate predictors of the occurrence of any arrhythmic end points, but multivariate Cox regression analysis indicated that only microvolt T-wave alternans was a significant independent predictor of risk. Thus, this study provides evidence that noninvasive risk stratification may be useful in patients with DCM, as opposed to ischemic cardiomyopathy, to identify those at risk of life-threatening ventricular arrhythmia in whom prophylactic treatment, including amiodarone or implantable-cardioverter defibrillator placement, may be warranted.
Prevalence of AF.
Tsang et al. (43) evaluated a resident population, reviewing demographic and medical data spanning a 30-year period, for evidence of a change in the prevalence of AF. A total of 1,871 (mean age 75 years) stroke cases and matched controls were evaluated. For stroke cases, age-adjusted estimates of AF prevalence for the years 1960 to 1969, 1970 to 1979, and 1980 to 1989 were 11%, 13%, and 16%, respectively, for men, and 13%, 16%, and 20%, respectively, for women. For controls, the rates were 5%, 8%, and 12%, respectively, for men, and 4%, 6%, and 8%, respectively, for women. An increasing prevalence of AF was observed to be associated with increasing age, calendar time (after adjusting for age), and gender. The rates of increase with calendar time were similar between the genders. The authors concluded that the prevalence of AF increased significantly in ischemic stroke patients and controls from 1960 to 1989, and that this increase was independent of both age and gender. These findings are of interest because they suggest that the apparent epidemic of AF in this country may not be entirely due to increased diligence on the part of physicians and the public to diagnose or detect AF. Rather, for as yet unknown epidemiologic reasons, there may actually be a greater prevalence (and probably incidence) of AF in the U.S. population today than that observed over the past four decades, not just due to our aging population.
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Cardiac therapeutics
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Aspirin resistance.
Aspirin has antiplatelet effects that reduce vascular events, but some patients are resistant to aspirin, with unknown consequences. Gum et al. (44) measured platelet aggregation in 326 patients with stable cardiovascular disease and found a 5% incidence of aspirin resistance. After a mean follow-up of two years, there was a greater likelihood of death, MI, or cerebrovascular accident in patients with aspirin resistance, compared with those without aspirin resistance (24% vs. 10%). This prospective trial demonstrated that aspirin resistance is not uncommon and influences clinical outcomes. In an editorial, Eikelboom and Hankey (45) noted it will be important to standardize the criteria and methodology for defining aspirin resistance to develop strategies to reduce thrombotic complications in these patients.
Myoblast transplantation.
Cell transplantation is a novel experimental approach to replace lost cardiomyocytes after MI to treat HF. Transplanting autologous skeletal muscle myoblasts provides potential advantages, including the ease of procuring an abundant number of cells that are resistance to ischemia and rejection. Menasche et al. (46) tested the feasibility and safety of this approach in a phase I human trial. Myoblasts grown from thigh muscle biopsies were injected into nonviable, akinetic LV scar tissue in 10 patients with LV dysfunction after MI. Two deaths occurred unrelated to cell transplantation, and four patients developed ventricular tachycardia that was managed with automatic implantable-cardioverter defibrillators. There was suggestion of improved regional and global LV function over 11 months, although the trial was not designed to test efficacy. Minami and Murry (47) note the importance of this as the first clinical study to demonstrate the feasibility and safety of transplanting skeletal myoblasts. This sets the stage for future clinical trials to evaluate efficacy using this novel approach.
Nitrate tolerance.
Continuous exposure to organic nitrates, such as transdermal glyceryl trinitrate, attenuates its therapeutic effectiveness. The mechanisms of nitrate tolerance may include impaired release of nitric oxide and increased superoxide generation in the vascular endothelium that may cause endothelial dysfunction. Muller et al. (48) examined nitrate tolerance in an experimental study in rabbits using isosorbide mononitrate with eccentric dosing (twice a day) similar to that used clinically. Mild nitrate tolerance developed at higher doses without increasing vascular superoxide production or impairing endothelial function. Thus, long-term therapy with this nitrate preparation can be used safely without aggravating endothelial dysfunction. Horowitz (49) noted that the induction of nitrate tolerance is nitrate-specific with variable effects on oxidative stress and endothelial dysfunction. The efficacy of nitrate therapy can be improved, while minimizing adverse effects on endothelial function by understanding the mechanisms of nitrate tolerance.
Myocardial preconditioning.
Brief episodes of myocardial ischemia have protective effects against subsequent episodes of ischemia, a phenomenon termed "preconditioning." An early phase of preconditioning that lasts for a few hours occurs clinically. There is a late phase of preconditioning that lasts for days, but this is not well established in humans. Lambiase et al. (50) found that exercise-induced ischemia triggers late preconditioning measured 24 h later in 30 patients with stable CAD. Preconditioning attenuated the effects of exercise or PCI on ST-segment changes on the ECG and was unrelated to changes in coronary collateral flow. Thus, exercise (at levels sufficient to induce ischemia) has myocardial protective effects against subsequent episodes of ischemia for at least 24 h in humans.
Peroxisome proliferator-activated receptor (PPAR)-gamma agonists.
The thiazolidinediones, including rosiglitazone, are insulin-sensitizing agents that target PPAR-gamma. The PPAR-gamma agonists have anti-inflammatory effects, including those on atherosclerotic plaques that express PPAR-gamma, and attenuate endothelial dysfunction. Sidhu et al. (51) investigated the potential benefits of rosiglitazone in 84 patients with stable CAD without diabetes mellitus. Compared with placebo, patients randomized to receive rosiglitazone for 12 weeks exhibited decreases in insulin resistance, markers of endothelial cell activation (E-selectin, von Willebrand factor), and acute-phase reactants (CRP and fibrinogen). Plutzky (52) noted the emerging potential role of PPAR-alpha agonists to target PPAR-alpha in vascular and inflammatory cells in atherosclerosis, in addition to diabetes mellitus and insulin resistance.
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Age and cardiac disease
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CAD in young adults.
Cole et al. (53) followed 843 patients under the age of 40 years old who were diagnosed with CAD by coronary angiography for 15 years. They concluded that coronary disease in young adults carries a poor long-term prognosis and that previous MI, diabetes, active tobacco abuse, and lower ejection fraction predicted significantly higher mortality. In an accompanying editorial comment, Klein and Nathan (54) noted that while the incidence of MI and symptomatic CAD in young adults is low, the consequences can be tragic. They also noted that young adults with CAD have a rapidly progressive form of the disease and that the traditional risk factors for CAD generally lack a strong association in these patients.
Quality of life after cardiac surgery in the elderly
Two articles in the October 2003 issue of JACC noted that quality-of-life improvements in elderly patients were comparable to those observed in younger patients after two different types of cardiac surgery.
Age and cardiac valve surgery
Sedrakyan et al. (55) prospectively studied 148 patients with aortic valve procedures and 72 patients with mitral valve procedures. They concluded that in patients referred for cardiac valve surgery, age does not appear to limit the quality-of-life benefits of surgery. In an accompanying editorial, Rumsfeld (56) noted that the primary implication of the study is that older patients undergoing cardiac valve surgery have significant improvements in quality of life, on par with the improvements seen in younger patients.
The elderly: health status benefits and recovery of function one year after coronary artery bypass graft surgery
Conaway et al. (57) compared the health status (symptoms, function, and quality of life) changes of elderly patients undergoing coronary artery bypass graft surgery to those of younger patients. They concluded that, despite a slower rate of physical recovery, older patients derived health status benefits from coronary artery bypass graft surgery similar to those of younger patients. In an accompanying editorial, Maurer (58) noted that age should not be considered a non-modifiable risk for worse outcomes and suggested that systems of care that address the possibilities of poor outcomes for older patients should be developed.
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Basic science
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Genetic polymorphisms affect the severity of atherosclerosis.
Traditional risk factors for atherosclerosis such as dyslipidemia, diabetes, hypertension, and smoking account for only a portion of the risk burden for atherosclerosis. Therefore, as we enter the genomic era of risk stratification, considerable effort has been applied toward identification of polymorphisms in the human genome that increase the risk for atherosclerosis. Single nucleotide polymorphisms are small genetic variations that can occur commonly (present in >0.5% to 1% of the population) within an individual's DNA sequence. Single nucleotide polymorphisms are distinct from and more common than a mutation where there is a change in a wild-type gene itself.
Given the large number of genes that could contribute to atherosclerosis and the polygenic nature of the disorder, it is a challenge to determine which of many polymorphisms are causally linked to disease. Glutamate-cysteine ligase is a rate-limiting enzyme for synthesis of glutathione that plays a crucial role in the intracellular antioxidant defense systems. Kugiyama et al. (59) demonstrated in a modest number of patients that a polymorphism in the glutamate-cysteine ligase catalytic subunit gene was associated with an increased risk of MI. Importantly, the authors also demonstrated that this polymorphism in the promoter region of the gene altered binding of a nuclear protein to the promoter, affected the expression of the gene, and had a functional effect on acetylcholine-induced coronary artery vasodilation. Although additional analysis with larger and more genetically diverse populations will be required to confirm the significance of these findings, this article demonstrates the importance of combining functional analysis of a polymorphism with population studies to determine which of the many polymorphisms that are identified are important in the pathogenesis of atherosclerotic disease.
Role for adenovirus infection in patients of all ages with myocarditis and DCM.
Infectious myocarditis and DCM have been associated with a number of different viruses, but coxsackievirus has been the most extensively studied. Towbin et al. (60) tested for the presence of a broad range of viruses from 624 patients with myocarditis and 149 patients with DCM using reverse transcription polymerase chain reaction or just polymerase chain reaction. Both pediatric and adult patients were evaluated. They demonstrated that 238 of the samples (38%) were positive for at least one virus. Of these, 142 samples were positive for adenoviral DNA, whereas 85 sample were positive for coxsackieviral ribonucleic acid. They also demonstrated that adenoviral DNA was present in samples from patients of all ages.
As pointed out by Baboonian and McKenna in the accompanying editorial (61), these findings are interesting from the perspective that the receptor for both viruses is the coxsackie-adenoviral receptor, indicating an important role for the interaction between coxsackie-adenoviral receptor and viruses that most commonly cause myocarditis. In addition, it indicates the probable importance of an under-recognized cause of myocarditis and DCM (i.e., adenoviral infection). Future mechanistic and therapeutic strategies for viral heart disease should consider these results.
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Cardiac imaging
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Identification of multivessel CAD.
A drawback of myocardial perfusion single-photon emission computed tomography (SPECT), or MPS, techniques is that patients with ischemia in multiple coronary territories often do not manifest perfusion defects in all ischemic territories due to the competitive nature of SPECT perfusion defect assessment. Lima et al. (62) hypothesized that by combining perfusion and function measurements with gated SPECT (Fig. 1 in Lima et al. [62]), identification of patients with multivessel perfusion abnormalities can be enhanced. These investigators studied 143 patients with angiographic three-vessel CAD and 112 control subjects. The MPS results were interpreted sequentially—first perfusion data only, followed by combined perfusion and function data. In patients with angiographic three-vessel CAD, the combination of perfusion and function data identified significantly more abnormal segments/patient (6.2 ± 4.7 vs. 4.1 ± 2.8, p < 0.001) and more defects in multiple vascular territories (60% vs. 46%, p < 0.05) than perfusion alone. On the other hand, there were no differences between the combined perfusion/function and perfusion alone interpretations in the control group. Multivariate modeling revealed patient age and the number of vascular territories determined to be abnormal by either perfusion or function analysis as the most powerful predictors of three-vessel CAD. This study established that functional data yielded incremental information over and above that yielded by clinical and perfusion data for predicting the presence of three-vessel CAD.
Risk after normal perfusion SPECT.
How long after a normal MPS study patients remain at low risk has yet to be examined. Hachamovitch et al. (63) addressed this issue in a study that identified 7,376 consecutive patients who had a normal exercise or adenosine MPS study. Over a mean follow-up of 1.8 years (96% complete), 78 hard events occurred, for an overall cumulative rate of 1.1%, or 0.6%/year in patients with a negative MPS. Significant increases in hard-event rates occurred in diabetic women, CAD patients undergoing exercise stress, and patients undergoing adenosine stress. Importantly, with respect to exercise stress, hard-event rates were higher in patients who achieved <80% of the predicted maximum heart rate. Cox proportional hazards analysis identified pharmacologic stress, known previous CAD, diabetes mellitus, male gender, and increasing age as the most significant predictors of hard events.
With respect to time and risk, in patients without previous CAD, the predicted risk increased significantly with age, with the presence of diabetes mellitus in women, and with adenosine stress. For any combination of clinical factors, the level of risk in these patients appeared to stay uniform year after year. However, for any combination of clinical factors in patients with known CAD, the risk increased with time. Hence, although a normal MPS study, in general, confers low risk, certain patient characteristics result in greater risk. The accelerating temporal characteristics of risk in patients with known CAD are probably explained by the CAD itself, whereas the majority of patients without known CAD who are found to have a normal MPS most likely do not have CAD.
Effect of beta-blockade on dipyridamole MPS.
Although it is well recognized that beta-blockers blunt the effects of exercise on MPS, whether these agents exert a similar effect on dipyridamole MPS is less well studied. Taillefer et al. (64) performed a prospective, double-blinded, placebo-controlled study in 21 patients with angiographically documented CAD. All patients underwent three dipyridamole sestamibi SPECT studies after intravenous placebo and low- and high-dose intravenous metoprolol. The sensitivity of dipyridamole MPS for detection of CAD was 86% with placebo versus 71% with low- and high-dose metoprolol. The sensitivity for detecting CAD in individual vessels was 69% with placebo versus 52% with metoprolol; the summed stress score was larger after placebo compared with either dose of metoprolol (p < 0.05). In an accompanying editorial, Gerson (65) ascribed the effect to an improvement of subendocardial flow secondary to the negative inotropic and chronotropic effects of the beta-blocker and suggested that cautious withdrawal of patients from beta-blockers before dipyridamole MPS should be considered.
Combined life-style and pharmacologic lipids.
The effects of aggressive medical management on myocardial perfusion and long-term outcomes were addressed by Sdringola et al. (66). They studied 324 patients undergoing dipyridamole myocardial perfusion positron emission tomography (PET) before and 2.6 years after the institution of medical therapy and repeated the PET study five years after the second scan. A maximal treatment group received intense life-style modification, including a diet containing <10% fat and exercise, as well as aggressive treatment of low- and high-density lipoprotein cholesterol; a moderate treatment group was treated with lipid-lowering drugs or dietary restriction, but not to the goals of the maximal group; a poor treatment group (n = 92) was actively smoking or not on a lipid reduction regimen. Patients in the maximal treatment group showed a significant improvement in the size/severity of perfusion abnormalities, whereas those in the moderate and poor treatment groups showed worsening of PET perfusion. Over the subsequent five-year follow-up, revascularization, MI, and cardiac death occurred in 6.6%, 20.3%, and 30.6% of the maximal, moderate, and poor treatment groups, respectively. By multivariate analysis, multiple clinical variables, including combined intense life-style change plus active lipid drugs, initial PET findings, and degree of PET improvement, were independent predictors of cardiac events. As editorialized by Parmley (67), although not a randomized clinical trial, this study provides evidence of the benefit of aggressive medical and life-style management on long-term outcomes and is also one of the largest studies to date demonstrating that improvement of stress myocardial perfusion on medical therapy is predictive of this benefit.
Delayed enhancement by magnetic resonance in hypertrophic cardiomyopathy (HCM).
Patients suffering a sudden cardiac death with HCM are known to have increased myocardial fibrosis. Delayed hyperenhancement on cardiac magnetic resonance after gadolinium injection has been shown to be a sensitive and specific marker of myocardial necrosis or fibrosis. Moon et al. (68) studied 53 patients with HCM, 23 of whom had two or more clinical markers of high risk for sudden death or had demonstrated progressive LV remodeling. Myocardial hyperenhancement was found in 42 patients, involving a mean of 10.9% of the LV mass, and was more extensive with progressive remodeling and in patients with a high risk of sudden death. This study, in combination with a study by Kim et al. (69), provides evidence that the unique capability of hyperenhancement cardiac magnetic resonance to define myocardial necrosis/fibrosis may be useful in assessing risk in HCM patients. Pending confirmation in larger trials, these findings may improve the identification of a subgroup of HCM patients warranting consideration of an implantable-cardioverter defibrillator to prevent sudden cardiac death.
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References
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1. Cosin-Sales J, Pizzi C, Brown S, Kaski JC. C-reactive protein, clinical presentation, and ischemic activity in patients with chest pain and normal coronary angiograms. J Am Coll Cardiol. 2003;41:1468–1474[Abstract/Free Full Text]
2. Landesberg G, Shatz V, Akopnik I, et al. Association of cardiac troponin, CK-MB, and postoperative myocardial ischemia with long-term survival following major vascular surgery. J Am Coll Cardiol. 2003;42:1547–1554[Abstract/Free Full Text]
3. Gibson CM, Pinto D, Murphy S, et al. Association of creatinine and creatinine clearance on presentation in acute myocardial infarction with subsequent mortality. J Am Coll Cardiol. 2003;42:1535–1543[Abstract/Free Full Text]
4. Zebrack JS, Anderson JL, Beddhu S, et al. Do associations with C-reactive protein and extent of coronary artery disease account for the increased cardiovascular risk of renal insufficiency? J Am Coll Cardiol. 2003;42:57–63[Abstract/Free Full Text]
5. Berger AK, Duval S, Krumholz HM. Aspirin, beta-blocker, and angiotensin-converting enzyme inhibitor therapy in patients with end-stage renal disease and an acute myocardial infarction. J Am Coll Cardiol. 2003;42:201–208[Abstract/Free Full Text]
6. Giugliano RP, Roe MT, Harrington RA, et al. Combination reperfusion therapy with eptifibatide and reduced-dose tenecteplase for ST-elevation myocardial infarction: results of the Integrilin and Tenecteplase in Acute Myocardial Infarction (INTEGRITI) phase II angiographic trial. J Am Coll Cardiol. 2003;41:1251–1260[Abstract/Free Full Text]
7. van der Horst ICC, Zijlstra F, van't Hof AWJ, et al. Glucose-insulin-potassium infusion in patients treated with primary angioplasty for acute myocardial infarction. J Am Coll Cardiol. 2003;42:784–791[Abstract/Free Full Text]
8. Antoniucci D, Rodriguez A, Hempel A, et al. A randomized trial comparing primary infarct artery stenting with or without abciximab in acute myocardial infarction. J Am Coll Cardiol. 2003;42:1880–1887
9. Topol E, Neumann FJ, Montalescot G. A preferred reperfusion strategy for acute myocardial infarction. J Am Coll Cardiol. 2003;42:1888–1891
10. Henriques JP, Haasdijk AP, Zijlstra F. Outcome of primary angioplasty for acute myocardial infarction during routine duty hours versus during off-hours. J Am Coll Cardiol. 2003;41:2138–2142[Abstract/Free Full Text]
11. Spencer FA, Becker RC. Circadian variations in acute myocardial infarction: patients or health care delivery? J Am Coll Cardiol. 2003;41:2143–2146[Free Full Text]
12. Scheller B, Hennen B, Hammer B, et al. Beneficial effects of immediate stenting after thrombolysis in acute myocardial infarction. J Am Coll Cardiol. 2003;42:634–641[Abstract/Free Full Text]
13. McKay RG. Evolving strategies in the treatment of acute myocardial infarction in the community hospital setting. J Am Coll Cardiol. 2003;42:642–645[Free Full Text]
14. Karvouni E, Katritsis DG, Ioannidis JP. Intravenous glycoprotein IIb/IIIa receptor antagonists reduce mortality after percutaneous coronary interventions. J Am Coll Cardiol. 2003;41:26–32[Abstract/Free Full Text]
15. Alfonso F, Zueco J, Cequier A, et al. A randomized comparison of repeat stenting with balloon angioplasty in patients with in-stent restenosis. J Am Coll Cardiol. 2003;42:796–805[Abstract/Free Full Text]
16. Albiero R, Silber S, Di Mario C, et al. Cutting balloon versus conventional balloon angioplasty for the treatment of in-stent restenosis: results of the REStenosis CUTting balloon evaluation trial (RESCUT). J Am Coll Cardiol 2004. In press
17. Degertekin M, Regar E, Tanabe K, et al. Sirolimus-eluting stent for treatment of complex in-stent restenosis: the first clinical experience. J Am Coll Cardiol. 2003;41:184–189[Abstract/Free Full Text]
18. Krumholz H, Epstein A, Rathore S, Volpp K. Hospital percutaneous coronary intervention volume and patient mortality, 1998 to 2000: does the evidence support current procedure volume minimums? J Am Coll Cardiol 2004. In press
19. Fang ZY, Yuda S, Anderson V, Short L, Case C, Marwick TH. Echocardiographic detection of early diabetic myocardial disease. J Am Coll Cardiol. 2003;41:611–617[Abstract/Free Full Text]
20. Gokce N, Keaney JF, Hunter LM, et al. Predictive value of noninvasively determined endothelial dysfunction for long-term cardiovascular events in patients with peripheral vascular disease. J Am Coll Cardiol. 2003;41:1769–1775[Abstract/Free Full Text]
21. Giglio V, Pasceri V, Messano L, et al. Ultrasound tissue characterization detects preclinical myocardial structural changes in children affected by Duchenne muscular dystrophy. J Am Coll Cardiol. 2003;42:309–316[Abstract/Free Full Text]
22. Towbin JA. A noninvasive means of detecting preclinical cardiomyopathy in Duchenne muscular dystrophy? (editorial comment). J Am Coll Cardiol. 2003;42:317–318[Free Full Text]
23. Heidenreich PA, Hancock SL, Lee BK, Mariscal CS, Schnittger I. Asymptomatic cardiac disease following mediastinal irradiation. J Am Coll Cardiol. 2003;42:743–749[Abstract/Free Full Text]
24. Byrd BF. Cardiac complications of mediastinal radiotherapy—the other side of the coin. (editorial comment). J Am Coll Cardiol. 2003;42:750–751[Free Full Text]
25. Garcia-Fernandez MA, Perez-David E, Quiles J, et al. Role of left atrial appendage obliteration in stroke reduction in patients with mitral valve prosthesis. J Am Coll Cardiol. 2003;42:1253–1258[Abstract/Free Full Text]
26. Blackshear JL, Johnson WD, Odell JA, et al. Thoracoscopic extracardiac obliteration of the left atrial appendage for stroke risk reduction in atrial fibrillation. J Am Coll Cardiol. 2003;42:1249–1252[Abstract/Free Full Text]
27. Halperin JL. Obliteration of the left atrial appendage for prevention of thromboembolism (editorial comment). J Am Coll Cardiol. 2003;42:1259–1261[Free Full Text]
28. Pitt B, Zannad F, Remme WJ, et al. The Randomized Aldactone Evaluation Study Investigators. The effect of spironolactone on morbidity and mortality in patients with severe heart failure. N Engl J Med. 1999;341:709–717[Abstract/Free Full Text]
29. Bozkurt B, Agoston I, Knowlton AA. Complications of inappropriate use of spironolactone in heart failure: when an old medicine spirals out of new guidelines. J Am Coll Cardiol. 2003;41:211–214[Abstract/Free Full Text]
30. Tang WHW, Francis GS. Spironolactone in chronic heart failure: all's well that ends well (editorial comment). J Am Coll Cardiol. 2003;41:215–216[Free Full Text]
31. Braith RW, Mills RM, Wilcox CS, David GL, Hill JA, Wood CE. High-dose angiotensin-converting enzyme inhibition restores body fluid homeostasis in heart-transplant recipients. J Am Coll Cardiol. 2003;41:426–432[Abstract/Free Full Text]
32. Eisen HJ. Hypertension in heart transplant recipients: more than just cyclosporine (editorial comment). J Am Coll Cardiol. 2003;41:433–434[Free Full Text]
33. Abbate A, Biondi-Zoccai GGL, Bussani R, et al. Increased myocardial apoptosis in patients with unfavorable left ventricular remodeling and early symptomatic post-infraction heart failure. J Am Coll Cardiol. 2003;41:753–760[Abstract/Free Full Text]
34. Mani K, Kitsis RN. Myocyte apoptosis: programming ventricular remodeling (editorial comment). J Am Coll Cardiol. 2003;41:761–764[Free Full Text]
35. Cice G, Ferrara L, D'Andrea A, et al. Carvedilol increases two-year survival in dialysis patients with dilated cardiomyopathy: a prospective, placebo-controlled trial. J Am Coll Cardiol. 2003;41:1438–1444[Abstract/Free Full Text]
36. Aquilani R, Opasich C, Verri M, et al. Is nutritional intake adequate in chronic heart failure patients? J Am Coll Cardiol. 2003;42:1218–1223[Abstract/Free Full Text]
37. Silver MA. Dietary research in heart failure: beyond the salt shaker (editorial comment). J Am Coll Cardiol. 2003;42:1224–1225[Free Full Text]
38. Leung RST, Bowman ME, Parker JD, Newton GE, Bradley TD. Avoidance of the left lateral decubitus position during sleep in patients with heart failure: relationship to cardiac size and function. J Am Coll Cardiol. 2003;41:227–230[Abstract/Free Full Text]
39. Manguso F, Pappone C, Santinelli V, et al. Usefulness of invasive electrophysiologic testing to stratify the risk of arrhythmic events in asymptomatic patients with Wolff-Parkinson-White pattern: results from a large prospective long-term follow-up study. J Am Coll Cardiol. 2003;41:239–244[Abstract/Free Full Text]
40. Pappone C, Rosanio S, Augello G, et al. Mortality, morbidity and quality of life after circumferential pulmonary vein ablation for atrial fibrillation: outcomes from a controlled not-randomized long-term study. J Am Coll Cardiol. 2003;42:185–197[Abstract/Free Full Text]
41. Berul C, Patel V, Arad M, et al. Electrophysiological characterization and postnatal development of ventricular preexcitation in a mouse model of cardiac hypertrophy and Wolff-Parkinson-White syndrome. J Am Coll Cardiol. 2003;42:942–951[Abstract/Free Full Text]
42. Hohnloser S, Klingenheben T, Bloomfield D, Daddous O, Cohen R. Usefulness of microvolt T wave alternans for prediction of ventricular tachyarrhythmic events in patients with dilated cardiomyopathy: results from a prospective observational study. J Am Coll Cardiol. 2003;41:2220–2224[Abstract/Free Full Text]
43. Tsang T, Petty GW, Barnes ME, et al. The prevalence of atrial fibrillation in incident stroke cases and matched population controls in Rochester, Minnesota: changes over three decades. J Am Coll Cardiol. 2003;42:93–100[Abstract/Free Full Text]
44. Gum PA, Kottke-Marchant K, Welsh PA, White J, Topol EJ. A prospective, blinded determination of the natural history of aspirin resistance among stable patients with cardiovascular disease. J Am Coll Cardiol. 2003;41:961–965[Abstract/Free Full Text]
45. Eikelboom JW, Hankey GJ. Aspirin resistance: a new independent predictor of vascular events? (editorial comment). J Am Coll Cardiol. 2003;41:966–968[Free Full Text]
46. Menasche P, Hagege AA, Vilquin JT, et al. Autologous skeletal myoblast transplantation for severe postinfarction of left ventricular dysfunction. J Am Coll Cardiol. 2003;41:1078–1083[Abstract/Free Full Text]
47. Minami E, Murry CE. Skeletal muscle meets cardiac muscle (editorial comment). J Am Coll Cardiol. 2003;41:1084–1086[Free Full Text]
48. Muller S, Laber U, Mullenheim J, Meyer W, Kojda G. Preserved endothelial function after long-term eccentric isosorbide mononitrate despite moderate nitrate tolerance. J Am Coll Cardiol. 2003;41:1994–2000[Abstract/Free Full Text]
49. Horowitz JD. Amelioration of nitrate tolerance: matching strategies with mechanisms (editorial comment). J Am Coll Cardiol. 2003;41:2001–2003[Free Full Text]
50. Lambiase PD, Edwards RJ, Cusack MR, Bucknall CA, Redwood SR, Marber MS. Exercise-induced ischemia initiates the second window of protection in humans independent of collateral recruitment. J Am Coll Cardiol. 2003;41:1174–1182[Abstract/Free Full Text]
51. Sidhu J, Cowan D, Kaski JC. The effects of rosiglitazone, a peroxisome proliferators-activated receptor-gamma agonist, on markers of endothelial cell activation, C-reactive protein, and levels in non-diabetic coronary artery disease patients. J Am Coll Cardiol. 2003;42:1757–1763[Abstract/Free Full Text]
52. Plutzky J. Peroxisome proliferators-activated receptors as therapeutic targets in inflammation (editorial comment). J Am Coll Cardiol. 2003;42:1764–1766[Free Full Text]
53. Cole JH, Miller JI 3rd, Sperling LS, Weintraub WS. Long-term follow-up of coronary artery disease presenting in young adults. J Am Coll Cardiol. 2003;41:521–528[Abstract/Free Full Text]
54. Klein LW, Nathan S. Coronary artery disease in young adults. J Am Coll Cardiol. 2003;41:529–531[Free Full Text]
55. Sedrakyan A, Vaccarino V, Paltiel AD, et al. Age does not limit quality of life improvement in cardiac valve surgery. J Am Coll Cardiol. 2003;42:1208–1214[Abstract/Free Full Text]
56. Rumsfeld JS. Valve surgery in the elderly: question of quality (of life)? J Am Coll Cardiol. 2003;42:1215–1217[Free Full Text]
57. Conaway DG, House J, Bandt K, Hayden L, Borkon AM, Spertus JA. The elderly: health status benefits and recovery of function 1-year after coronary artery bypass surgery. J Am Coll Cardiol. 2003;42:1421–1426[Abstract/Free Full Text]
58. Maurer MS. Age: a non-modifiable risk factor? (editorial comment). J Am Coll Cardiol. 2003;42:1427–1428[Free Full Text]
59. Kugiyama K, Koide S, Sugiyama S, et al. Association of polymorphism in the glutamate-cysteine ligase catalytic subunit gene with coronary vasomotor dysfunction and myocardial infarction. J Am Coll Cardiol. 2003;41:539–545[Abstract/Free Full Text]
60. Towbin J, Bowles JE, Ni J, et al. Detection of viruses in myocardial tissues by polymerase chain reaction: evidence of adenovirus as a common cause of myocarditis in children and adults. J Am Coll Cardiol. 2003;42:466–472[Abstract/Free Full Text]
61. Baboonian C, McKenna W. Eradication of viral myocarditis: is there a hope? J Am Coll Cardiol. 2003;42:473–476[Free Full Text]
62. Lima RSL, Watson DD, Goode AR, Siadaty MS, Ragosta M, Beller GA, Samady H. Incremental value of combined perfusion and function over perfusion alone by gated SPECT myocardial perfusion imaging for detection of severe three-vessel coronary artery disease. J Am Coll Cardiol. 2003;42:64–70[Abstract/Free Full Text]
63. Hachamovitch R, Hayes S, Friedman JD, et al. Determinants of risk and its temporal variation in patients with normal stress myocardial perfusion scans: what is the warranty period of a normal scan? J Am Coll Cardiol. 2003;41:1329–1340[Abstract/Free Full Text]
64. Taillefer R, Ahlberg AW, Masood Y, et al. Acute beta-blockade reduces the extent and severity of myocardial perfusion defects with dipyridamole Tc-99m sestamibi SPECT imaging. J Am Coll Cardiol. 2003;42:1475–1483[Abstract/Free Full Text]
65. Gerson MC. Reduction in dipyridamole-induced single-photon emission computed tomography myocardial defect size by beta-blockers: time to re-examine the patient preparation protocol for pharmacologic stress testing. (editorial comment)J Am Coll Cardiol. 2003;42:1484–1485[Free Full Text]
66. Sdringola S, Nakagawa K, Nakagawa Y, et al. Combined intense lifestyle and pharmacologic lipid treatment further reduce coronary events and myocardial perfusion abnormalities compared with usual-care cholesterol-lowering drugs in coronary artery disease. J Am Coll Cardiol. 2003;41:263–272[Abstract/Free Full Text]
67. Parmley WW. In the statin era, how important are intense lifestyle changes? (editorial comment). J Am Coll Cardiol. 2003;41:273–274[Free Full Text]
68. Moon JCC, McKenna WJ, McCrohon JA, Elliott PM, Smith GC, Pennell DJ. Toward clinical risk assessment in hypertrophic cardiomyopathy with gadolinium cardiovascular magnetic resonance. J Am Coll Cardiol. 2003;41:1561–1567[Abstract/Free Full Text]
69. Kim R, Choudhury L, Maahrholdt H, et al. Myocardial scarring in asymptomatic and mildly symptomatic patients with hypertrophic cardiomyopathy. J Am Coll Cardiol. 2002;40:2156–2164[Abstract/Free Full Text]
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Coronary artery disease/acute...
Interventional cardiology