Ian R. Starkey

Randomized Trial of Simple Versus Complex Drug-Eluting Stenting for Bifurcation Lesions The British Bifurcation Coronary Study: Old, New, and Evolving Strategies

Background The optimal strategy for treating coronary bifurcation lesions remains a subject of debate. With bare-metal stents, single-stent approaches appear to be superior to systematic 2-stent strategies. Drug-eluting stents, however, have low rates of restenosis and might offer improved outcomes with complex stenting techniques. Methods and Results Patients with significant coronary bifurcation lesions were randomized to either a simple or complex stenting strategy with drug-eluting stents. In the simple strategy, the main vessel was stented, followed by optional kissing balloon dilatation/T-stent. In the complex strategy, both vessels were systematically stented (culotte or crush techniques) with mandatory kissing balloon dilatation. Five hundred patients 64 10 years old were randomized; 77% were male. Eighty-two percent of lesions were true bifurcations ( 50% narrowing in both vessels). In the simplegroup (n 250), 66 patients (26%) had kissing balloons in addition to main-vessel stenting, and 7 (3%) had T stenting. In the complex group (n 250), 89% of culotte (n 75) and 72% of crush (n 169) cases were completed successfully with final kissing balloon inflations. The primary end point (a composite at 9 months of death, myocardial infarction, and target-vessel failure) occurred in 8.0% of the simple group versus 15.2% of the complex group (hazard ratio 2.02, 95% confidence interval 1.17 to 3.47, P 0.009). Myocardial infarction occurred in 3.6% versus 11.2%, respectively (P 0.001), and in-hospital major adverse cardiovascular events occurred in 2.0% versus 8.0% (P 0.002), respectively. Procedure duration and x-ray dose favored the simple approach. Conclusions When coronary bifurcation lesions are treated, a systematic 2-stent technique results in higher rates of in-hospital and 9-month major adverse cardiovascular events. This difference is largely driven by periprocedural myocardial infarction. Procedure duration is longer, and x-ray dose is higher. The provisional technique should remain the preferred strategy in the majority of cases.Background— The optimal strategy for treating coronary bifurcation lesions remains a subject of debate. With bare-metal stents, single-stent approaches appear to be superior to systematic 2-stent strategies. Drug-eluting stents, however, have low rates of restenosis and might offer improved outcomes with complex stenting techniques. Methods and Results— Patients with significant coronary bifurcation lesions were randomized to either a simple or complex stenting strategy with drug-eluting stents. In the simple strategy, the main vessel was stented, followed by optional kissing balloon dilatation/T-stent. In the complex strategy, both vessels were systematically stented (culotte or crush techniques) with mandatory kissing balloon dilatation. Five hundred patients 64±10 years old were randomized; 77% were male. Eighty-two percent of lesions were true bifurcations (>50% narrowing in both vessels). In the simple group (n=250), 66 patients (26%) had kissing balloons in addition to main-vessel stenting, and 7 (3%) had T stenting. In the complex group (n=250), 89% of culotte (n=75) and 72% of crush (n=169) cases were completed successfully with final kissing balloon inflations. The primary end point (a composite at 9 months of death, myocardial infarction, and target-vessel failure) occurred in 8.0% of the simple group versus 15.2% of the complex group (hazard ratio 2.02, 95% confidence interval 1.17 to 3.47, P=0.009). Myocardial infarction occurred in 3.6% versus 11.2%, respectively (P=0.001), and in-hospital major adverse cardiovascular events occurred in 2.0% versus 8.0% (P=0.002), respectively. Procedure duration and x-ray dose favored the simple approach. Conclusions— When coronary bifurcation lesions are treated, a systematic 2-stent technique results in higher rates of in-hospital and 9-month major adverse cardiovascular events. This difference is largely driven by periprocedural myocardial infarction. Procedure duration is longer, and x-ray dose is higher. The provisional technique should remain the preferred strategy in the majority of cases. Clinical Trial Registration Information— URL: http://www.clinicaltrials.gov. Unique identifier: NCT 00351260.

Randomised study comparing complex versus simple drug-eluting stent strategies for coronary bifurcations

Background The optimal strategy for treating coronary bifurcation lesions remains a subject of debate. With bare-metal stents, single-stent approaches appear to be superior to systematic 2-stent strategies. Drug-eluting stents, however, have low rates of restenosis and might offer improved outcomes with complex stenting techniques. Methods and Results Patients with significant coronary bifurcation lesions were randomized to either a simple or complex stenting strategy with drug-eluting stents. In the simple strategy, the main vessel was stented, followed by optional kissing balloon dilatation/T-stent. In the complex strategy, both vessels were systematically stented (culotte or crush techniques) with mandatory kissing balloon dilatation. Five hundred patients 64 10 years old were randomized; 77% were male. Eighty-two percent of lesions were true bifurcations ( 50% narrowing in both vessels). In the simplegroup (n 250), 66 patients (26%) had kissing balloons in addition to main-vessel stenting, and 7 (3%) had T stenting. In the complex group (n 250), 89% of culotte (n 75) and 72% of crush (n 169) cases were completed successfully with final kissing balloon inflations. The primary end point (a composite at 9 months of death, myocardial infarction, and target-vessel failure) occurred in 8.0% of the simple group versus 15.2% of the complex group (hazard ratio 2.02, 95% confidence interval 1.17 to 3.47, P 0.009). Myocardial infarction occurred in 3.6% versus 11.2%, respectively (P 0.001), and in-hospital major adverse cardiovascular events occurred in 2.0% versus 8.0% (P 0.002), respectively. Procedure duration and x-ray dose favored the simple approach. Conclusions When coronary bifurcation lesions are treated, a systematic 2-stent technique results in higher rates of in-hospital and 9-month major adverse cardiovascular events. This difference is largely driven by periprocedural myocardial infarction. Procedure duration is longer, and x-ray dose is higher. The provisional technique should remain the preferred strategy in the majority of cases.Background— The optimal strategy for treating coronary bifurcation lesions remains a subject of debate. With bare-metal stents, single-stent approaches appear to be superior to systematic 2-stent strategies. Drug-eluting stents, however, have low rates of restenosis and might offer improved outcomes with complex stenting techniques. Methods and Results— Patients with significant coronary bifurcation lesions were randomized to either a simple or complex stenting strategy with drug-eluting stents. In the simple strategy, the main vessel was stented, followed by optional kissing balloon dilatation/T-stent. In the complex strategy, both vessels were systematically stented (culotte or crush techniques) with mandatory kissing balloon dilatation. Five hundred patients 64±10 years old were randomized; 77% were male. Eighty-two percent of lesions were true bifurcations (>50% narrowing in both vessels). In the simple group (n=250), 66 patients (26%) had kissing balloons in addition to main-vessel stenting, and 7 (3%) had T stenting. In the complex group (n=250), 89% of culotte (n=75) and 72% of crush (n=169) cases were completed successfully with final kissing balloon inflations. The primary end point (a composite at 9 months of death, myocardial infarction, and target-vessel failure) occurred in 8.0% of the simple group versus 15.2% of the complex group (hazard ratio 2.02, 95% confidence interval 1.17 to 3.47, P=0.009). Myocardial infarction occurred in 3.6% versus 11.2%, respectively (P=0.001), and in-hospital major adverse cardiovascular events occurred in 2.0% versus 8.0% (P=0.002), respectively. Procedure duration and x-ray dose favored the simple approach. Conclusions— When coronary bifurcation lesions are treated, a systematic 2-stent technique results in higher rates of in-hospital and 9-month major adverse cardiovascular events. This difference is largely driven by periprocedural myocardial infarction. Procedure duration is longer, and x-ray dose is higher. The provisional technique should remain the preferred strategy in the majority of cases. Clinical Trial Registration Information— URL: http://www.clinicaltrials.gov. Unique identifier: NCT 00351260.

Value of the electrocardiogram in identifying heart failure due to left ventricular systolic dysfunction

Chronic heart failure due to left ventricular systolic dysfunction has a high morbidity and mortality. Angiotensin converting enzyme inhibitors reduce symptomatic deterioration, hospitalisation, and death. Most patients with suspected heart failure present first to general practitioners. Recent studies have emphasised the difficulty of diagnosing heart failure in the community. Fewer than half of patients treated for heart failure by general practitioners have objective evidence of cardiac disease.1 2 To improve diagnosis and treatment Dargie and McMurray suggested that echocardiography should be performed in all patients suspected of having chronic heart failure.3 Screening patients before referral for diagnostic investigation may lessen the considerable resource implications of this approach. We assessed the value of the electrocardiogram in identifying patients with possible chronic heart failure. An open access echocardiography …

Differences in myocardial velocity gradient measured throughout the cardiac cycle in patients with hypertrophic cardiomyopathy, athletes and patients with left ventricular hypertrophy due to hypertension

OBJECTIVES We sought to compare the myocardial velocity gradient (MVG) measured across the left ventricular (LV) posterior wall during the cardiac cycle between patients with hypertrophic cardiomyopathy (HCM), athletes and patients with LV hypertrophy due to systemic hypertension and to determine whether it might be used to discriminate these groups. BACKGROUND The MVG is a new ultrasound variable, based on the color Doppler technique, that quantifies the spatial distribution of transmyocardial velocities. METHODS A cohort of 158 subjects was subdivided by age into two groups: Group I (mean [+/-SD] 30 +/- 7 years) and Group II (58 +/- 8 years). Within each group there were three categories of subjects: Group Ia consisted of patients with HCM (n = 25), Group Ib consisted of athletes (n = 21), and Group Ic consisted of normal subjects; Group IIa consisted of patients with HCM (n = 19), Group IIb consisted of hypertensive patients (n = 27), and Group IIc consisted of normal subjects (n = 33). RESULTS The MVG (mean [+/-SD] s-1) measured in systole was lower (p < 0.01) in patients with HCM (Group Ia 3.2 +/- 1.1; Group IIa 2.9 +/- 1.2) compared with athletes (Group Ib 4.6 +/- 1.1), hypertensive patients (Group IIb 4.2 +/- 1.8) and normal subjects (Group Ic 4.4 +/- 0.8; Group IIc 4.8 +/- 0.8). In early diastole, the MVG was lower (p < 0.05) in patients with HCM (Group Ia 3.7 +/- 1.5; Group IIa 2.6 +/- 0.9) than in athletes (Group Ib 9.9 +/- 1.9) and normal subjects (Group Ic 9.2 +/- 2.0; Group IIc 3.6 +/- 1.5), but not hypertensive patients (Group IIb 3.3 +/- 1.3). In late diastole, the MVG in patients with HCM (Group Ia 1.3 +/- 0.8; Group IIa 1.4 +/- 0.8) was lower (p < 0.01) than that in hypertensive patients (Group IIb 4.3 +/- 1.7) and normal subjects (Group IIc 3.8 +/- 0.9). An MVG < or = 7 s-1, as a single diagnostic approach, differentiated accurately (0.96 positive and 0.94 negative predictive value) between patients with HCM and athletes when the measurements were taken during early diastole. CONCLUSIONS In both age groups, the MVG was lower in both systole and diastole in patients with HCM than in athletes, hypertensive patients or normal subjects. The MVG measured in early diastole in a group of subjects 18 to 45 years old would appear to be an accurate variable used to discriminate between HCM and hypertrophy in athletes.

Open access echocardiography in management of heart failure in the community.

Abstract Objective: To assess the value of an open access echocardiography service. Design: Study of new open access service for general practitioners, who were invited to refer patients taking diuretics for suspected heart failure, untreated patients with symptoms of possible heart failure, and asymptomatic patients with risk factors for left ventricular systolic dysfunction. Setting: Regional cardiology centre. Subjects: 259 consecutive patients. Main outcome measures: Presence or absence of left ventricular systolic dysfunction and consequent changes in clinical management. Results: 119 treated patients, 99 untreated patients, and nine asymptomatic patients were referred over five months. 32 were considered to be inappropriately referred. Among the treated patients, 31 had impaired left ventricular systolic function and five had valvular disease; angiotensin converting enzyme inhibitors were recommended for 34 of these patients. In addition, 53 were thought not to need diuretics. Eight untreated patients had impaired systolic function and six valvular disease. Conclusions: The service was well used by general practitioners and led to advice to change management in more than two thirds of patients. Key messages Key messages Without accurate diagnosis many patients will be treated inappropriately Echocardiography allows rapid confirmation of the diagnosis Providing general practitioners with open access to echocardiography led to a change in treatment being recommended for 70% of patients taking diuretics for suspected heart failure The open access service was popular with general practitioners and did not lead to an unmanageable increase in workload

Predisposing factors for cerebral infarction: the Oxfordshire community stroke project.

The frequency of known causative factors of cerebral infarction was studied in 244 cases of first ever stroke due to cerebral infarction proved by computed tomography or at necropsy who were registered in the first two years of a prospective community based study. Risk factors for cerebral infarction were present in 196 (80%) cases; hypertension in 126 (52%); ischaemic heart disease in 92 (38%); peripheral vascular disease in 60 (25%); a cardiac lesion that was a major potential source of embolism to the brain in 50 (20%); transient ischaemic attacks in 35 (14%); cervical arterial bruit in 33 (14%); and diabetes mellitus in 24 (10%). Thirty one patients (13%) were in atrial fibrillation. Of the 48 patients who were free of risk factors or a major potential cardiac source of embolism at the time of the stroke, 18 were found to have hypertension after the stroke and 10 to have non-atheromatous non-embolic conditions (migrainous cerebral infarction (three), arteritis (two), inflammatory bowel disease (one), arterial trauma (one), autoimmune disease (one), carcinoma of the thyroid (one), and major operation (one). In 20 patients no causative factors could be identified. In this unselected series of patients with first ever stroke due to cerebral infarction most of the strokes were presumed to be due to either atheromatous arterial disease or embolism from the heart, and only 4% (95% confidence interval 2 to 7%) were probably due to non-atheromatous non-embolic causes. This has implications for research into strokes and allocation of public health expenditure.

Characterisation of coronary atherosclerotic morphology by spectral analysis of radiofrequency signal: in vitro intravascular ultrasound study with histological and radiological validation

Objective To determine whether spectral analysis of unprocessed radiofrequency (RF) signal offers advantages over standard videodensitometric analysis in identifying the morphology of coronary atherosclerotic plaques. Methods 97 regions of interest (ROI) were imaged at 30 MHz from postmortem, pressure perfused (80 mm Hg) coronary arteries in saline baths. RF data were digitised at 250 MHz. Two different sizes of ROI were identified from scan converted images, and relative amplitudes of different frequency components were analysed from raw data. Normalised spectra was used to calculate spectral slope (dB/MHz), y-axis intercept (dB), mean power (dB), and maximum power (dB) over a given bandwidth (17–42 MHz). RF images were constructed and compared with comparative histology derived from microscopy and radiological techniques in three dimensions. Results Mean power was similar from dense fibrotic tissue and heavy calcium, but spectral slope was steeper in heavy calcium (−0.45 (0.1)) than in dense fibrotic tissue (−0.31 (0.1)), and maximum power was higher for heavy calcium (−7.7 (2.0)) than for dense fibrotic tissue (−10.2 (3.9)). Maximum power was significantly higher in heavy calcium (−7.7 (2.0) dB) and dense fibrotic tissue (−10.2 (3.9) dB) than in microcalcification (−13.9  (3.8) dB). Y-axis intercept was higher in microcalcification (−5.8 (1.1) dB) than in moderately fibrotic tissue (−11.9  (2.0) dB). Moderate and dense fibrotic tissue were discriminated with mean power: moderate −20.2 (1.1) dB, dense −14.7 (3.7) dB; and y-axis intercept: moderate −11.9 (2.0) dB, dense −5.5  (5.4) dB. Different densities of fibrosis, loose, moderate, and dense, were discriminated with both y-axis intercept, spectral slope, and mean power. Lipid could be differentiated from other types of plaque tissue on the basis of spectral slope, lipid −0.17 (0.08). Also y-axis intercept from lipid (−17.6 (3.9)) differed significantly from moderately fibrotic tissue, dense fibrotic tissue, microcalcification, and heavy calcium. No significant differences in any of the measured parameters were seen between the results obtained from small and large ROIs. Conclusion Frequency based spectral analysis of unprocessed ultrasound signal may lead to accurate identification of atherosclerotic plaque morphology.

Diltiazem in acute myocardial infarction treated with thrombolytic agents: a randomised placebo-controlled trial

BACKGROUND Diltiazem reduces non-fatal reinfarction and refractory ischaemia after non-Q-wave myocardial infarction, an acute coronary syndrome similar to the incomplete infarction that occurs after successful reperfusion. We postulated that this agent would reduce cardiac events in patients after acute myocardial infarction treated initially with thrombolytic agents-a clinical application previously unexplored with heart-rate-lowering calcium antagonists. METHODS A prospective, randomised, double-blind, sequential trial was done in 874 patients with acute myocardial infarction, but without congestive heart failure, who first received thrombolytic agents. Patients received either 300 mg oral diltiazem once daily, or placebo, initiated within 36-96 h of infarct onset, and given for up to 6 months. The trial primary endpoint was the cumulative first event rate of cardiac death, non-fatal reinfarction, or refractory ischaemia. Additional prespecified endpoints included several composites of non-fatal cardiac events (non-fatal reinfarction combined with refractory ischaemia, all recurrent ischaemia, or the need for myocardial revascularisation). The diagnosis of ischaemia, whether refractory or recurrent, and the need for myocardial revascularisation, was always based on objective electrocardiographical evidence of ischaemia, either at rest or on exertion. RESULTS For the trial primary endpoint, 131 events occurred in the 444 placebo patients and 97 events in the 430 diltiazem patients (hazard ratio 0.79; 95% CI, 0.61-1.02; p=0.07). For non-fatal cardiac events, diltiazem treatment was associated with a relative decrease (0.76; 0.58-1.00) in the combined event rate of non-fatal reinfarction and refractory ischaemia. There was a similar decrease in the composite non-fatal endpoints of non-fatal reinfarction combined with all recurrent ischaemia (0.80; 0.64-1.00) and non-fatal reinfarction combined with the need for myocardial revascularisation (0.67; 0.46-0.96). The need for myocardial revascularisation alone was significantly reduced by 42% (0.61; 0.39-0.96). No major safety issues were encountered. CONCLUSIONS Diltiazem did not reduce the cumulative occurrence of cardiac death, non-fatal reinfarction, or refractory ischaemia during a 6-month follow-up, but did reduce all composite endpoints of non-fatal cardiac events, especially the need for myocardial revascularisation.

Contemporary management of acute coronary syndromes: does the practice match the evidence? The global registry of acute coronary events (GRACE)

Objective: To determine to what extent evidence based guidelines are followed in the management of acute coronary syndromes (ACS) in the UK, elsewhere in Europe, and multinationally, and what the outcomes are. Design: Multinational, prospective, observational registry (GRACE, global registry of acute coronary events) with six months’ follow up. Setting: Patients presenting to a cluster of hospitals. The study was designed to collect data representative of the full spectrum of ACS in specific geographic populations. Patients: Patients admitted with a working diagnosis of unstable angina or suspected myocardial infarction (MI). Main outcome measures: Death during hospitalisation and at six months’ follow up (adjusted for baseline risks). Results: In ST elevation MI, reperfusion was applied more often in the UK (71%) than in Europe (65%) and multinationally (59%) (p < 0.01). However, this was almost entirely by lytic treatment, in contrast with elsewhere (primary percutaneous coronary intervention 1%, 29%, 16%, respectively). Statins were applied more frequently in the UK for all classes of patients with ACS (p < 0.0001). In contrast there was lower use of revascularisation procedures in non-ST MI (20% v 37% v 28%, respectively) and glycoprotein IIb/IIIa antagonists (6% v 25% v 26%, respectively). In-hospital death rates, adjusted for baseline risk, were not significantly different but six month death rates were higher in the UK for ST elevation MI (7.2% UK, 4.3% Europe, 5.3% multinationally; p < 0.0001) and non-ST elevation MI (7.5%, 6.2%, and 6.7%, respectively; p  =  0.012, UK v Europe). Conclusions: Current management of ACS in the UK more closely follows the recommendations of the National Service Framework than British or European guidelines. Differences in practice may account for the observed higher event rates in the UK after hospital discharge.

Reduced vascular complications and length of stay with transradial rescue angioplasty for acute myocardial infarction

The aim of this study was to compare clinical outcomes for transradial and transfemoral percutaneous coronary intervention in patients with ST‐segment elevation myocardial infarction undergoing rescue angioplasty.