A Placebo-Controlled Trial of Percutaneous Coronary Intervention for Stable Angina.

BACKGROUND: Percutaneous coronary intervention (PCI) is frequently performed to reduce the symptoms of stable angina. Whether PCI relieves angina more than a placebo procedure in patients who are not receiving antianginal medication remains unknown. METHODS: We conducted a double-blind, randomized, placebo-controlled trial of PCI in patients with stable angina. Patients stopped all antianginal medications and underwent a 2-week symptom assessment phase before randomization. Patients were then randomly assigned in a 1:1 ratio to undergo PCI or a placebo procedure and were followed for 12 weeks. The primary end point was the angina symptom score, which was calculated daily on the basis of the number of angina episodes that occurred on a given day, the number of antianginal medications prescribed on that day, and clinical events, including the occurrence of unblinding owing to unacceptable angina or acute coronary syndrome or death. Scores range from 0 to 79, with higher scores indicating worse health status with respect to angina. RESULTS: A total of 301 patients underwent randomization: 151 to the PCI group and 150 to the placebo group. The mean (±SD) age was 64±9 years, and 79% were men. Ischemia was present in one cardiac territory in 242 patients (80%), in two territories in 52 patients (17%), and in three territories in 7 patients (2%). In the target vessels, the median fractional flow reserve was 0.63 (interquartile range, 0.49 to 0.75), and the median instantaneous wave-free ratio was 0.78 (interquartile range, 0.55 to 0.87). At the 12-week follow-up, the mean angina symptom score was 2.9 in the PCI group and 5.6 in the placebo group (odds ratio, 2.21; 95% confidence interval, 1.41 to 3.47; P<0.001). One patient in the placebo group had unacceptable angina leading to unblinding. Acute coronary syndromes occurred in 4 patients in the PCI group and in 6 patients in the placebo group. CONCLUSIONS: Among patients with stable angina who were receiving little or no antianginal medication and had objective evidence of ischemia, PCI resulted in a lower angina symptom score than a placebo procedure, indicating a better health status with respect to angina. (Funded by the National Institute for Health and Care Research Imperial Biomedical Research Centre and others; ORBITA-2 ClinicalTrials.gov number, NCT03742050.).

Adjunctive Intracoronary Fibrinolytic Therapy During Primary Percutaneous Coronary Intervention.

Despite routinely restoring epicardial coronary patency, with primary percutaneous coronary intervention (PCI), microvascular obstruction affects approximately half of patients and confers an adverse prognosis. There are no evidence-based treatments for microvascular obstruction. A key contributor to microvascular obstruction is distal embolisation and microvascular thrombi. Adjunctive intracoronary fibrinolytic therapy may reduce thrombotic burden, potentially reducing distal embolisation of atherothrombotic debris to the microcirculation. In this review, the evidence from published randomised trials on the effects of adjunctive intracoronary fibrinolytic therapy during primary PCI is critically appraised, the ongoing randomised trials are described, and conclusions are made from the available evidence. Clinical uncertainties, to be addressed by future research, are highlighted.

DIAGNOSIS AND MANAGEMENT OF BENIGN PROSTATIC HYPERPLASIA IN A PIED TAMARIN (SAGUINUS BICOLOR).

An intact male pied tamarin (Saguinus bicolor) presented with a hunched posture while moving, dysuria, pollakiuria, and hematuria. After diagnostic imaging assessment and prostate biopsy, benign prostatic hyperplasia was diagnosed. Treatments with delmadinone acetate and osaterone caused clinical signs and hematuria to resolve temporarily for a variable period of time. Because of frequent recurrence, elective surgical castration was performed, leading to resolution of the clinical signs.

Patent foramen ovale closure following cryptogenic stroke or transient ischaemic attack: Long-term follow-up of 301 cases.

Patent foramen ovale has been identified as a conduit for paradoxical embolism resulting in cryptogenic stroke or transient ischemic attack (TIA). We aimed to establish rates of death, recurrent stroke or TIA among patients undergoing PFO closure for stroke or TIA at our unit. A retrospective analysis of all PFO closure patients was performed between May 2004 and January 2013. Follow up was performed by mortality tracing using the Medical Research Information Service of the Office of National Statistics. With regard to stroke or TIA recurrence, written consent forms and questionnaires were mailed with follow up telephone calls. Medical notes and imaging records were consulted where adverse events were noted. 301 patients aged 48.6 ± 11.0 years, 54.4% male, with ≥1 thromboembolic neurovascular event had percutaneous PFO closure with one of eight devices, with successful implantation in 99% of cases. Follow-up duration was 40.2 ± 26.2 months (range 1.3-105.3); complete in 301 patients for mortality (100%) and 283 patients (94.0%) for neurovascular events. Two patients died during follow-up (respiratory failure n = 1; road traffic accident n = 1). Recurrent stroke (MRI or CT confirmed) was observed in five patients (0.5%; 0.55 per 100 person-years) and TIA in 9 (1.1%; 0.98 per 100 person-years). Atrial fibrillation requiring treatment was documented in 14 patients (1.7%). Percutaneous PFO closure in patients with cryptogenic stroke or TIA is a safe treatment with a low incidence of procedural complications and recurrent neurovascular events. Registry data like these may help to demonstrate the utility of PFO closure in stroke.

Symptoms as a Predictor of the Placebo-Controlled Efficacy of PCI in Stable Coronary Artery Disease.

BACKGROUND: Placebo-controlled evidence from ORBITA-2 (Objective Randomised Blinded Investigation with Optimal Medical Therapy of Angioplasty in Stable Angina-2) found that percutaneous coronary intervention (PCI) in stable coronary artery disease with little or no antianginal medication relieved angina, but residual symptoms persisted in many patients. The reason for this was unclear. OBJECTIVES: This ORBITA-2 secondary analysis investigates the relationship between presenting symptoms and disease severity (anatomic, noninvasive, and invasive ischemia) and the ability of symptoms to predict the placebo-controlled efficacy of PCI. METHODS: Prerandomization symptom severity and nature were assessed using the ORBITA smartphone application and symptom and quality of life questionnaires including the World Health Organization Rose angina questionnaire (Rose). Disease severity was assessed using quantitative coronary angiography, stress echocardiography, fractional flow reserve, and instantaneous wave-free ratio. Bayesian ordinal regression was used. RESULTS: At prerandomization, the median number of daily angina episodes was 0.8 (Q1-Q3: 0.4-1.6), 64% had Rose angina, quantitative coronary angiography diameter stenosis was 61% (Q1-Q3: 49%-74%), stress echocardiography score was 1.0 (Q1-Q3: 0.0-2.7), fractional flow reserve was 0.63 (Q1-Q3: 0.49-0.75), and instantaneous wave-free ratio was 0.78 (Q1-Q3: 0.55-0.87). There was little relationship between symptom severity and nature and disease severity: angina symptom score with quantitative coronary angiography ordinal correlation coefficient: 0.06 (95% credible interval [CrI]: 0.00-0.08); stress echocardiography: 0.09 (95% CrI: 0.02-0.10); fractional flow reserve: 0.04 (95% CrI: -0.03 to 0.07); and instantaneous wave-free ratio: 0.04 (95% CrI: -0.01 to 0.07). However, Rose angina and guideline-based typical angina were strong predictors of placebo-controlled PCI efficacy (angina symptom score: OR: 1.9; 95% CrI: 1.6-2.1; probability of interaction [PrInteraction] = 99.9%; and OR: 1.8; 95% CrI: 1.6-2.1; PrInteraction = 99.9%, respectively). CONCLUSIONS: Although symptom severity and nature were poorly associated with disease severity, the nature of symptoms powerfully predicted the placebo-controlled efficacy of PCI.

Effect of coronary tortuosity on invasive physiology.

We present a case of angina, where extreme coronary tortuosity affected invasive physiology interpretation. Extreme coronary tortuosity may lower fractional flow reserve and instantaneous wave-free ratio. Therefore, invasive physiology can be misleading in this setting, when used to evaluate stenosis significance, or when used post-percutaneous coronary (PCI) intervention for physiology guided stent optimisation.

Revascularisation or medical therapy in elderly patients with acute anginal syndromes: the RINCAL randomised trial.

BACKGROUND: Historically the elderly have been under-represented in non-ST-elevation myocardial infarction (NSTEMI) management trials. AIMS: The aim of this trial was to demonstrate that an intervention-guided strategy is superior to optimal medical therapy (OMT) alone for treating NSTEMI in elderly individuals. METHODS: Patients (≥80 years, chest pain, ischaemic ECG, and elevated troponin) were randomised 1:1 to an intervention-guided strategy plus OMT versus OMT alone. The primary endpoint was a composite of all-cause mortality and non-fatal myocardial reinfarction at 1 year. Ethics approval was obtained by the institutional review board of every recruiting centre. RESULTS: From May 2014 to September 2018, 251 patients (n=125 invasive vs n=126 conservative) were enrolled. Almost 50% of participants were female. The trial was terminated prematurely due to slow recruitment. A Kaplan-Meier estimate of event-free survival revealed no difference in the primary endpoint at 1 year (invasive 18.5% [23/124] vs conservative 22.2% [28/126]; p=0.39). No significant difference persisted after Cox proportional hazards regression analysis (hazard ratio 0.79, 95% confidence interval 0.45-1.35; p=0.39). There was greater freedom from angina at 3 months (p<0.001) after early intervention but this was similar at 1 year. Both non-fatal reinfarction (invasive 9.7% [12/124] vs conservative 14.3% [18/126]; p=0.22) and unplanned revascularisation (invasive 1.6% [2/124] vs conservative 6.4% [8/126]; p=0.10) occurred more frequently in the OMT alone cohort. CONCLUSIONS: An intervention-guided strategy was not superior to OMT alone to treat very elderly NSTEMI patients. The trial was underpowered to demonstrate this definitively. Early intervention resulted in fewer cases of reinfarction and unplanned revascularisation but did not improve survival.

Decreasing operators' radiation exposure during coronary procedures: the transradial radiation protection board.

AIM: Transradial coronary procedures are associated with decreased vascular access site complications and other benefits compared to the femoral approach. There is some concern however about high-recorded radiation doses for interventional cardiologists using the transradial route. We therefore designed and investigated the effect of a transradial radiation protection board (TRPB) on operator radiation exposure during coronary procedures. METHODS AND RESULTS: One hundred and six patients were randomly assigned by time period to undergo radial coronary procedures either with or without a TRPB. This is a grooved arm board with a detachable 0.5-mm lead equivalent shield designed to rest between the patient's arm and side. Individual case-specific radiation exposures were measured using electronic personal dosimeter worn on the left outer pocket of the lead apron at chest level. The TRPB was used in addition to standard lead apron and thyroid shielding, below-table leaded flaps, and leaded glass. Operator radiation exposure was significantly decreased in the TRPB group overall: 28 [18-65] microSV versus 19.5 [10.5-35] microSV, P = 0.003. There were no significant differences in procedure duration, total fluoroscopy dose, or contrast load between the two groups. conclusion: Identification of methods to reduce operator radiation dose is important. The use of the TRPB can significantly reduce radiation exposure to radial operators.

Predictors for permanent pacing after transcatheter aortic valve implantation.

BACKGROUND: Transcatheter aortic valve implantation (TAVI) is a new treatment strategy for patients with symptomatic aortic stenosis who are high risk for traditional surgical aortic valve replacement. The incidence of conduction system abnormalities after the procedure is significant. We examine our experience with CoreValve TAVI focusing on electrocardiographic changes found pre-, peri-, and postintervention. METHODS: During 2007-08 we undertook 33 cases utilizing the CoreValve revalving system (CoreValve, Paris, France). Assessment of ECGs, with particular reference to the PR and QRS duration, was made daily during each patient's hospital stay. RESULTS: Patients were aged 81.7 ± 6.7 years and the majority were male (57%). Baseline cardiac rhythm was sinus (n = 28, 80%); atrial fibrillation (n = 6, 18%) or ventricular paced (n = 1, 3%). Following CoreValve implantation, prolongation of both the PR interval and QRS duration was seen. Preprocedural PR interval was 193.5 ± 38.7 ms and QRS interval preprocedure was 115.3 ± 24.8 ms. PR interval increased after the procedure by 23.5 ± 23.9 ms and peaked at day 4 with a mean increase of 66.1 ± 72.7 ms. QRS duration increased by a mean of 30.6 ± 26.1 ms postprocedure and remained stable thereafter during the remaining hospital stay. The need for PPM insertion was partially predicted by pre-procedural QRS morphology: patients with pre-existing right bundle branch block had an 83% chance of requiring a permanent pacemaker (P < 0.01 OR 28 95%CI 2.4-326.7); those with LBBB had a 33% chance of requiring a pacemaker (P = ns OR 2.3 95%CI 0.2-34.9). Patients undergoing the procedure later in our experience showed a decreased incidence of pacing (P = 0.046 OR 0.36 95% CI 0.07-1.82). Pre-procedural annulus measurements also predicted the requirement for pacing with larger annulus sizes more likely to require a pacemaker (P = 0.044 OR 3.3 95% CI 0.63-17.6). The requirement for pacing was not predicted by age, baseline PR interval or gender. Requirement for pacing overall was 32% with an additional 13% having had a pacemaker inserted prior to the TAVI. CONCLUSION: CoreValve insertion was associated with an increase in PR interval and QRS duration. PR interval continued to rise during admission, peaking on Day 4 post procedure, making a prolonged period of monitoring highly desirable. There was a significant requirement for permanent pacing, which was predicted by pre-procedural QRS morphology, annulus measurement, and the learning curve. © 2010 Wiley-Liss, Inc.

Prognostic benefit of transcatheter aortic valve implantation compared with medical therapy in patients with inoperable aortic stenosis.

OBJECTIVES: To compare survival in patients with inoperable aortic stenosis who undergo transcatheter aortic valve implantation against those managed medically. BACKGROUND: Without surgical correction, survival of patients with severe symptomatic aortic stenosis is poor. It is unknown whether patients undergoing transcatheter aortic valve implantation (TAVI) have a better prognosis than similar patients who are treated with medical management. METHODS: Survival rates were compared in consecutive patients with severe symptomatic aortic stenosis who either underwent TAVI or continued on medical management following multidisciplinary team assessment. All patients had been turned down, or considered at unacceptably high risk, for conventional aortic valve surgery. Patients were reviewed in clinic or by telephone six monthly. Mortality data was obtained from the United Kingdom Office of National Statistics. RESULTS: The study group included 85 patients aged 81 +/- 7 years (range 62-94), of whom 48 were male. Thirty eight patients underwent TAVI while 47 patients were deemed unsuitable based on echocardiographic, angiographic, or clinical criteria and remained on medical therapy. The calculated EuroSCORE for the TAVI group was 11 +/- 2 and for the medical group 9 +/- 2 (P < 0.001). TAVI-related procedural mortality was 2.6%, and 30-day mortality was 5.2%. Among the medically-treated patients, 14 (30%) underwent palliative balloon aortic valvuloplasty, with a trend toward improved survival (P = 0.06). During overall follow-up of 215 +/- 115 days there were a total of 18 deaths; TAVI N = 5 (13%); Medical N = 13 (28%) (P = 0.04). CONCLUSIONS: Patients with severe aortic valve disease who are not suitable for surgical aortic valve replacement have an improved prognosis if treated with transcatheter aortic valve implantation rather than continuing on medical management alone.

Percutaneous aortic valve implants under sedation: our initial experience.

OBJECTIVES: We have developed an approach where percutaneous aortic valve (PAVI) procedures are done under remifentanil-based sedation administered by an anesthetist. We report here our initial experience. BACKGROUND: Percutaneous aortic valve implantation is proving to be an effective treatment for aortic stenosis in patients with significant comorbidity precluding surgical aortic valve replacement. Most PAVIs have been done under general anesthetic with transoesophageal echocardiography (TOE). General anesthesia in this patient group is hazardous and associated with significant complications. METHODS AND RESULTS: CoreValve implantation was performed via the retrograde approach in 12 patients at our cardiothoracic center between December 2007 and May 2008. Three had the procedure under general anesthetic and nine under sedation. There were no differences between the groups in terms of comorbidities and clinical characteristics. The procedure was visualized using fluoroscopic aortic calcification coupled with multiple small volume aortograms. One patient converted from sedation to general anesthetic during the procedure. One patient in the general anesthetic group died from respiratory complications. There were no significant differences in procedural success, procedure time, or hospital stay between the two groups. CONCLUSION: Percutaneous aortic valve implantation can, in the majority of cases, be performed under remifentanil-based sedation. Our initial experience suggests that this should result in a shorter implant procedure time, reduced stay in high dependency areas, and shorter time to hospital discharge.

First-in-human use of the OneShot™ renal denervation system from Covidien.

Percutaneous transcatheter renal sympathetic denervation (RDN) is a promising treatment for refractory hypertension (HT). RDN was found in one series of clinical studies to reduce systolic blood pressure (SBP) by as much as a mean of 30 mmHg with 85% of subjects experiencing sustained reductions of 10 mm or more out to two years after RDN. This degree of blood pressure reduction may reduce stroke and myocardial infarction rates and is anticipated to translate into improved life expectancy. The lowering of blood pressure by RDN has been shown to improve glycaemic control and reverse left ventricular hypertrophy. Beneficial effects on renal function, sleep apnoea and heart failure are suggested as well. This report describes the first patient treated using the OneShot™ Renal Denervation System (formerly Maya Medical now Covidien, Campbell, CA, USA).

Inorganic coatings for cardiovascular stents: In vitro and in vivo studies.

The in-vitro and in-vivo biocompatibility of two oxides (TiO and ZrO) and diamond-like carbon (D) coated stents has been assessed and compared with uncoated stainless steel (St) stents. In vitro studies demonstrated that both fibrinogen adsorption and platelet adhesion were significantly higher on D coating compared to those on oxide coatings and uncoated stainless steel. In addition TiO and ZrO coatings showed evidence of a minor inflammatory response and more complete endothelialization of the aorta than that seen around D coated and uncoated St stents. The resulting neointimal growth in the aorta with TiO, ZrO, and D coated and uncoated St stents, measured 8 weeks after stenting (the ratio of the neointima in the stented artery to the non-stented artery) was 1.03 + 0.28, 0.85 + 0.36, 1.78 + 1.26, and 1.15 + 0.56, accordingly. From the data obtained it could be concluded that the increased neointima measured around D-coated stents, may be due to both, the inferior haemocompatibility of the diamond-like carbon coating and mechanical instability of D coating observed in an in vivo environment.

Transcatheter aortic valve implantation for stenosed and regurgitant aortic valve bioprostheses CoreValve for failed bioprosthetic aortic valve replacements.

Transcatheter aortic valve implantation is increasingly being used to treat severe aortic stenosis in patients with high operative risk. In an aging population the incidence of aortic stenosis is rising, and increasing numbers of elderly patients are undergoing aortic valve replacement with bioprosthetic valves. Therefore, there is a corresponding increase in prosthetic degeneration. This presents cardiologists with a cohort of patients for whom the risk of re-do aortic valve surgery is prohibitive. We present the first series of such patients with degenerative bioprosthetic stenosis or regurgitation successfully treated with CoreValve (Medtronic, Luxembourg) implantation.

Patent foramen ovale closure without echocardiographic control: use of "standby" intracardiac ultrasound.

OBJECTIVES: Our aim was to develop a "standby intracardiac echocardiography" approach to patent foramen ovale (PFO) closures where intracardiac echocardiography (ICE) is only utilized where there are adverse features. BACKGROUND: Percutaneous closure of PFO is usually aided by transesophageal echocardiography or ICE. This may be unnecessary where anatomical features are straightforward. METHODS: Patients were excluded from standby ICE if they had adverse anatomical features on their diagnostic transoesophageal echocardiogram, a device other than Amplatzer (AGA Medical, Plymouth, Minnesota), STARflex (NMT Medical, Boston, Massachusetts), or BioSTAR (NMT Medical) were to be used, or they were in a clinical trial demanding ICE/transesophageal echocardiography. Procedurally, defect diameter >15 mm on balloon sizing and tunnel length >12 mm warranted ICE guidance. RESULTS: Between April 2006 and October 2007, 124 patients underwent PFO closure. Fifty-four were excluded from standby ICE due to trial protocols (n = 22), hybrid atrial septal defect/PFO (n = 6), additional defect (n = 4), exuberant aneurysm (n = 3), or other device (n = 19, all HELEX, Gore Medical, Flagstaff, Arizona). The remaining 70 patients were age 38.1 +/- 6.4 years, 49% men. Primary indication for PFO closure was stroke (n = 46, 65%), transient ischemic attack (n = 22, 31%), or decompression illness (n = 2, 3%). Sixty-four (91%) underwent contrast fluoroscopic PFO closure alone. Six patients (9%) converted to ICE-controlled closure: PFO sized to >15 mm (n = 2); difficulties crossing PFO (n = 2), or long tunnel requiring transseptal puncture (n = 2). All 70 patients had procedural success without significant complications. Procedure duration and cost favored standby ICE. CONCLUSIONS: PFO closure can, in the majority of cases, be performed safely using contrast media and fluoroscopy alone. Standby ICE facilitates closure in the remaining patients during the index procedure.