James T. Stewart

Comparison of Percutaneous Coronary Intervention and Coronary Artery Bypass Grafting After Acute Myocardial Infarction Complicated by Cardiogenic Shock Results From the Should We Emergently Revascularize Occluded Coronaries for Cardiogenic Shock (SHOCK) Trial

Background—The Should We Emergently Revascularize Occluded Coronaries for Cardiogenic Shock (SHOCK) trial demonstrated the survival advantage of emergency revascularization versus initial medical stabilization in patients developing cardiogenic shock after acute myocardial infarction. The relative merits of coronary artery bypass grafting (CABG) versus percutaneous coronary intervention (PCI) in patients with shock have not been defined. The objective of this analysis was to compare the effects of PCI and CABG on 30-day and 1-year survival in the SHOCK trial. Methods and Results—Of the 302 trial patients, 128 with predominant left ventricular failure had emergency revascularization. The selection of revascularization procedures was individualized. Eighty-one patients (63.3%) had PCI, and 47 (36.7%) had CABG. The median time from randomization to intervention was 0.9 hours (interquartile range [IQR], 0.3 to 2.2 hours) for PCI and 2.7 hours (IQR, 1.3 to 5.5 hours) for CABG. Baseline demographics and hemodynamics were similar, except that there were more diabetics (48.9% versus 26.9%; P=0.02), 3-vessel disease (80.4% versus 60.3%; P=0.03), and left main coronary disease (41.3% versus 13.0%; P=0.001) in the CABG group. In the PCI group, 12.3% had 2-vessel and 2.5% had 3-vessel interventions. In the CABG group, 84.8% received ≥2 grafts, 52.2% received ≥3 grafts, and 87.2% were deemed completely revascularized. The survival rates were 55.6% in the PCI group compared with 57.4% in the CABG group at 30 days (P=0.86) and 51.9% compared with 46.8%, respectively, at 1 year (P=0.71). Conclusions—Among SHOCK trial patients randomized to emergency revascularization, those treated with CABG had a greater prevalence of diabetes and worse coronary disease than those treated with PCI. However, survival rates were similar. Emergency CABG is an important component of an optimal treatment strategy in patients with cardiogenic shock, and should be considered a complementary treatment option in patients with extensive coronary disease.

Drug-eluting stents for coronary bifurcations: Bench testing of provisional side-branch strategies

The objective of this study was to bench‐test provisional bifurcation stenting strategies to provide insights on how best to perform these with drug‐eluting stents (DESs). Bifurcation stenting with DESs reduces restenosis compared with bare metal stents (BMSs). Outcomes with a single DES are better than with two DESs but if the main branch is stented, there needs to be a reliable strategy for provisionally stenting the side‐branch with full ostial scaffolding and drug application. Stents were photographed in a phantom after deployment with different strategies. With provisional T‐stenting, placement of the side‐branch stent without gaps is difficult. The internal (or reverse) crush strategy fully scaffolds the side‐branch ostium but is experimental. The culotte technique providing excellent side‐branch ostial coverage is easier to perform with open‐cell or large‐cell stent design. In general, kissing balloon postdilatation improves stent expansion, especially at the ostium, and corrects distortion. However, a main‐branch kissing balloon of smaller diameter than the deploying balloon causes distortion. Final main‐branch postdilatation or sequential postdilatation prevents distortion after the internal crush strategy.

Novel organ-specific circulating cardiac autoantibodies in dilated cardiomyopathy

To determine whether organ-specific cardiac autoantibodies are present in dilated cardiomyopathy, indirect immunofluorescence on human heart and skeletal muscle was used to test sera from 200 normal subjects and from 65 patients with dilated cardiomyopathy, 41 with chronic heart failure due to myocardial infarction and 208 with other cardiac disease. Three immunofluorescence patterns were observed: diffuse cytoplasmic on cardiac tissue only (organ-specific), fine striational on cardiac and, to a lesser extent, skeletal muscle (cross-reactive 1) and broad striational on both cardiac and skeletal muscle (cross-reactive 2). Cardiac specificity of the cytoplasmic pattern was confirmed by absorption studies with homogenates of human atrium, skeletal muscle and rat liver. Organ-specific cardiac antibodies (IgG; titer range 1/10 to 1/80) were more frequent in patients with dilated cardiomyopathy (17 [26%] of 65) than in those with other cardiac disease (2 [1%] of 208, p less than 0.0001) or heart failure (0 [0%] of 41, p less than 0.001) or in normal subjects (7 [3.5%] of 200, p less than 0.0001). Organ-specific cardiac antibodies were more common in patients with dilated cardiomyopathy and in those with fewer symptoms (8 of 15 in New York Heart Association functional class I versus 9 of 50 in classes II to IV, p less than 0.01) and more recent (less than 2 years) onset of disease (9 of 19 versus 8 of 46, p less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

Drug-eluting stents for coronary bifurcations: insights into the crush technique.

Sirolimus‐eluting stents appear to reduce substantially restenosis following percutaneous coronary bifurcation intervention. The crush technique was devised to reduce restenosis further by improving stent and drug application to the side‐branch ostium. We aimed to investigate the performance of drug‐eluting stent (DES) platforms with the crush technique, to identify deployment pitfalls, and to clarify the best deployment strategies. Each stage of the crush technique was photographed in a bifurcation phantom. Simultaneous side‐ and main‐branch dilatation (kissing balloons) fully expanded the stent in the side‐branch ostium, widened the gaps between stent struts covering the side branch, and eliminated main‐branch distortion. With side branches angled at > 70°, sequential (side‐ then main‐branch) inflations may be needed to achieve best results. Postdilatation of the main branch with a balloon of narrower diameter than the deploying balloon caused main‐branch stent distortion. These principles applied to all the bifurcation strategies and stent designs tested. Cathet Cardiovasc Interv 2004;63:332–336.

The Pharmacogenetics and Pharmacodynamics of Clopidogrel Response: An Analysis From the PRINC (Plavix Response in Coronary Intervention) Trial

OBJECTIVES This study assessed the effect of pharmacogenetics on the antiplatelet effect of clopidogrel. BACKGROUND Variability in clopidogrel response might be influenced by polymorphisms in genes coding for drug metabolism enzymes (cytochrome P450 [CYP] family), transport proteins (P-glycoprotein) and/or target proteins for the drug (adenosine diphosphate-receptor P2Y12). METHODS Sixty patients undergoing elective percutaneous coronary intervention in the randomized PRINC (Plavix Response in Coronary Intervention) trial had platelet function measured using the VerifyNow P2Y12 analyzer after a 600-mg or split 1,200-mg loading dose and after a 75- or 150-mg daily maintenance dosage. Polymerase chain reaction-based genotyping evaluated polymorphisms in the CYP2C19, CYP2C9, CYP3A4, CYP3A5, ABCB1, P2Y12, and CES genes. RESULTS CYP2C19*1*1 carriers had greater platelet inhibition 2 h after a 600-mg dose (median: 23%, range: 0% to 66%), compared with platelet inhibition in CYP2C19*2 or *4 carriers (10%, 0% to 56%, p = 0.029) and CYP2C19*17 carriers (9%, 0% to 98%, p = 0.026). CYP2C19*2 or *4 carriers had greater platelet inhibition with the higher loading dose than with the lower dose at 4 h (37%, 8% to 87% vs. 14%, 0% to 22%, p = 0.002) and responded better with the higher maintenance dose regimen (51%, 15% to 86% vs. 14%, 0% to 67%, p = 0.042). CONCLUSIONS Carriers of the CYP2C19*2 and *4 alleles showed reduced platelet inhibition after a clopidogrel 600-mg loading dose but responded to higher loading and maintenance dose regimens. Genotyping for the relevant gene polymorphisms may help to individualize and optimize clopidogrel treatment. (Australia New Zealand Clinical Trials Registry; ACTRN12606000129583).

Hypertrophic cardiomyopathy without hypertrophy: two families with myocardial disarray in the absence of increased myocardial mass.

Two families are described in which individuals showed widespread myocardial disarray at histological examination, in the absence of macroscopic cardiac hypertrophy. In one family the clinical presentation was that of sudden unexpected cardiac death in four family members; members of the other family presented with electrocardiographic repolarisation changes and abnormalities of left ventricular diastolic function. The finding of myocardial disarray, the characteristic histological abnormality of hypertrophic cardiomyopathy, in the absence of increased cardiac mass suggests a wider range of abnormality in hypertrophic cardiomyopathy than is currently recognised.

A next-generation bioresorbable coronary scaffold system: from bench to first clinical evaluation: 6- and 12-month clinical and multimodality imaging results.

OBJECTIVES This study sought to perform clinical and imaging assessments of the DESolve Bioresorbable Coronary Scaffold (BCS). BACKGROUND BCS, which is drug eluting, may have potential advantages compared with conventional metallic drug-eluting stents. The DESolve system, designed to provide vessel support and neointimal suppression, combines a poly-l-lactic acid-based scaffold with the antiproliferative myolimus. METHODS The DESolve First-in-Man (a non-randomized, consecutive enrollment evaluation of the DESolve myolimus eluting bioresorbable coronary stent in the treatment of patients with de novo native coronary artery lesions) trial was a prospective multicenter study enrolling 16 patients eligible for treatment. The principal safety endpoint was a composite of cardiac death, myocardial infarction, and clinically indicated target lesion revascularization. The principal imaging endpoint was in-scaffold late lumen loss (LLL) assessed by quantitative coronary angiography (QCA) at 6 months. Intravascular ultrasound (IVUS) and optical coherence tomography (OCT) imaging was performed at baseline and 6 months; multislice computed tomography (MSCT) was performed at 12 months. RESULTS Acute procedural success was achieved in 15 of 15 patients receiving a study scaffold. At 12 months, there was no scaffold thrombosis and no major adverse cardiac events directly attributable to the scaffold. At 6 months, in-scaffold LLL (by QCA) was 0.19 ± 0.19 mm; neointimal volume (by IVUS) was 7.19 ± 3.56%, with no evidence of scaffold recoil or late malapposition. Findings were confirmed with OCT and showed uniform, thin neointimal coverage (0.12 ± 0.04 mm). At 12 months, MSCT demonstrated excellent vessel patency. CONCLUSIONS This study demonstrated the feasibility and efficacy of the DESolve BCS. Results showing low in-scaffold LLL, low % neointimal volume at 6 months, no chronic recoil, and maintenance of lumen patency at 12 months prompt further study. (DESolve First-in-Man; EudraCT number 2011-000027-32).

Renal denervation for resistant hypertension using an irrigated radiofrequency balloon: 12-month results from the Renal Hypertension Ablation System (RHAS) trial

AIMS Renal denervation using the point-by-point application of radiofrequency energy delivered by the first-generation Symplicity system is effective in lowering office blood pressure but may be time-consuming. The OneShot Renal Denervation System with a balloon-mounted spiral electrode potentially shortens and simplifies the procedure. This study is a hypothesis-generating first-in-human study to assess feasibility, and to provide preliminary efficacy and safety data. METHODS AND RESULTS Eligible patients had a baseline office systolic blood pressure ≥160 mmHg (or ≥150 mmHg for diabetics) and were on two or more antihypertensive medications. Nine patients were enrolled. The primary endpoint, the insertion of the OneShot balloon into each renal artery and the delivery of radiofrequency energy, was achieved in 8/9 (89%) of patients. The one failure (the first patient) was due to generator high-impedance safety shut-off threshold set too low for humans. Adverse events were minor. No patient developed renal artery stenosis. Baseline BP was 185.67 ± 18.7 mmHg and the reductions at 1, 3, 6 and 12 months were 30.1 ± 13.6 (p=0.0004), 34.2 ± 20.2 (p=0.002), 33.6 ± 32.2 (p=0.021) and 30.6 ± 22.0 (p=0.019). CONCLUSIONS The OneShot renal denervation system successfully delivered radiofrequency energy to the renal arteries in a short and straightforward procedure. Australian New Zealand Clinical Trials Registry - URL: anzctr.org.au. Trial identification: ACTRN12611000987965.

Ventricular fibrillation in hypertrophic cardiomyopathy is associated with increased fractionation of paced right ventricular electrograms.

BackgroundIntraventricular conduction in hypertrophic cardiomyopathy (HCM) has been characterized to test the hypothesis that myofibrillar disarray will cause dispersion of activation throughout the ventricular myocardium. Methods and ResultsOf 37 patients with HCM, four had spontaneous ventricular fibrillation (VF), five had nonsustained ventricular tachycardia (VT), 13 had no risk factors, and 15 had a family history of sudden death. These patients and four controls were studied by pacing one site in the right ventricle and recording electrograms from three other right ventricular sites. These electrograms were high-pass filtered to emphasize small deflections due to activation of small bundles of myocytes close to the electrode. Intraventricular conduction curves were obtained with S1S2 coupling intervals decreasing in 1-msec steps from 479 msec to ventricular effective refractory period (VERP). These curves were repeated by pacing each RV site in turn and were characterized by two parameters: the point at which latency increased by 0.75 msec/20 msec reduction of the S1S2 coupling interval and an increase in electrogram duration between an S1S2 of 350 msec and VERP. Patients with VF, VT, and family history of sudden death had a mean increase in electrogram duration of 12.8 (2.9–32.3) msec versus 4.6 (−4.2 to 14.0) msec in low-risk patients and controls. Electrogram latency increased at an S1S2 of 363 msec in the VF group (342–386), 269 msec in the controls (266–279), and 326 msec in the non-VF group (260–399). Discriminant analysis separated VF patients from the remainder (p < 0.0001) and VF, VT, and family history of sudden death patients from the low-risk and control groups (p < 10−6). ConclusionsPatients with HCM who are at nrsk of sudden death have increased dispersion and inhomogeneity of intraventricular conduction, and this may create the conditions for reentry and arrhythmogenesis.

Stent longitudinal flexibility : A comparison of 13 stent designs before and after balloon expansion

Longitudinal flexibility is an important property of coronary stents, facilitating delivery and allowing the expanded stent to conform to vessel contour. Subjective descriptions of flexibility abound, but there are few independent quantitative data to aid stent selection. A three‐point bend test was employed to measure stiffness, the reciprocal of flexibility, for 13 stent designs in the unexpanded (bare) state, then after expansion with a 3.5‐mm balloon. For eight of the designs, stiffness of the proprietary stent/balloon delivery system was also measured. In the unexpanded state, there was a wide spread of stiffness, which ranged from 0.5 ± 0.2 to 91.5 ± 10.0 g force/mm, depending on design. Stiffness was least for the coil (Wiktor and Crossflex) and hybrid (AVE GFX and Bard XT) designs. The MultiLink was the most flexible and the Crown the stiffest of the slotted tube designs. All stents became stiffer upon expansion. For most manufacturer‐mounted stents, the delivery balloon was the main determinant of stent/balloon delivery system stiffness. Manufacturer‐mounted stent profile ranged from 1.15 ± 0.11 mm for the Jostent to 1.53 ± 0.05 mm for the MultiLink system. Independent quantitative assessment of characteristics such as flexibility and profile should aid rational comparison of stent designs. Cathet. Cardiovasc. Intervent. 50:120–124, 2000.