Saqib Chowdhary

Consensus standards for acquisition, measurement, and reporting of intravascular optical coherence tomography studies: a report from the International Working Group for Intravascular Optical Coherence Tomography Standardization and Validation.

OBJECTIVES The purpose of this document is to make the output of the International Working Group for Intravascular Optical Coherence Tomography (IWG-IVOCT) Standardization and Validation available to medical and scientific communities, through a peer-reviewed publication, in the interest of improving the diagnosis and treatment of patients with atherosclerosis, including coronary artery disease. BACKGROUND Intravascular optical coherence tomography (IVOCT) is a catheter-based modality that acquires images at a resolution of ~10 μm, enabling visualization of blood vessel wall microstructure in vivo at an unprecedented level of detail. IVOCT devices are now commercially available worldwide, there is an active user base, and the interest in using this technology is growing. Incorporation of IVOCT in research and daily clinical practice can be facilitated by the development of uniform terminology and consensus-based standards on use of the technology, interpretation of the images, and reporting of IVOCT results. METHODS The IWG-IVOCT, comprising more than 260 academic and industry members from Asia, Europe, and the United States, formed in 2008 and convened on the topic of IVOCT standardization through a series of 9 national and international meetings. RESULTS Knowledge and recommendations from this group on key areas within the IVOCT field were assembled to generate this consensus document, authored by the Writing Committee, composed of academicians who have participated in meetings and/or writing of the text. CONCLUSIONS This document may be broadly used as a standard reference regarding the current state of the IVOCT imaging modality, intended for researchers and clinicians who use IVOCT and analyze IVOCT data.

Randomized Trial of Primary PCI with or without Routine Manual Thrombectomy

BACKGROUND During primary percutaneous coronary intervention (PCI), manual thrombectomy may reduce distal embolization and thus improve microvascular perfusion. Small trials have suggested that thrombectomy improves surrogate and clinical outcomes, but a larger trial has reported conflicting results. METHODS We randomly assigned 10,732 patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary PCI to a strategy of routine upfront manual thrombectomy versus PCI alone. The primary outcome was a composite of death from cardiovascular causes, recurrent myocardial infarction, cardiogenic shock, or New York Heart Association (NYHA) class IV heart failure within 180 days. The key safety outcome was stroke within 30 days. RESULTS The primary outcome occurred in 347 of 5033 patients (6.9%) in the thrombectomy group versus 351 of 5030 patients (7.0%) in the PCI-alone group (hazard ratio in the thrombectomy group, 0.99; 95% confidence interval [CI], 0.85 to 1.15; P=0.86). The rates of cardiovascular death (3.1% with thrombectomy vs. 3.5% with PCI alone; hazard ratio, 0.90; 95% CI, 0.73 to 1.12; P=0.34) and the primary outcome plus stent thrombosis or target-vessel revascularization (9.9% vs. 9.8%; hazard ratio, 1.00; 95% CI, 0.89 to 1.14; P=0.95) were also similar. Stroke within 30 days occurred in 33 patients (0.7%) in the thrombectomy group versus 16 patients (0.3%) in the PCI-alone group (hazard ratio, 2.06; 95% CI, 1.13 to 3.75; P=0.02). CONCLUSIONS In patients with STEMI who were undergoing primary PCI, routine manual thrombectomy, as compared with PCI alone, did not reduce the risk of cardiovascular death, recurrent myocardial infarction, cardiogenic shock, or NYHA class IV heart failure within 180 days but was associated with an increased rate of stroke within 30 days. (Funded by Medtronic and the Canadian Institutes of Health Research; TOTAL ClinicalTrials.gov number, NCT01149044.).

Nitric Oxide and Cardiac Autonomic Control in Humans

Cardiac autonomic control is of prognostic significance in cardiac disease, yet the control mechanisms of this system remain poorly defined. Animal data suggest that nitric oxide (NO) modulates cardiac autonomic control. We investigated the influence of NO on the baroreflex control of heart rate in healthy human subjects. In 26 healthy male volunteers (mean age, 23+/-5 years), we measured heart rate variability and baroreflex sensitivity during inhibition of endogenous NO production with N(G)-monomethyl-L-arginine (L-NMMA) (3 mg/kg per hour) and during exogenous NO donation with sodium nitroprusside (1 to 3 mg/h). Increases from baseline (Delta) in high-frequency (HF) indexes of heart rate variability were smaller with L-NMMA in comparison to an equipressor dose of the control vasoconstrictor phenylephrine (12 to 42 microg/kg per hour): Deltaroot mean square of successive RR interval differences (DeltaRMSSD)=23+/-32 versus 51+/-48 ms (P<0.002); Deltapercentage of successive RR interval differences >50 ms (DeltapNN50)=5+/-15% versus 14+/-12% (P<0.05); and DeltaHF normalized power=-2+/-7 versus 9+/-8 normalized units (P<0.01), respectively. Relative preservation of these indexes was observed during unloading of the baroreflex with sodium nitroprusside compared with a matched fall in blood pressure produced by a control vasodilator, hydralazine (9 to 18 mg/h): DeltaRMSSD=-8+/-8 versus -24+/-15 ms (P<0.001); DeltapNN50=-6+/-11% versus -15+/-19% (P<0.01); DeltaHF normalized power=-7+/-13 versus -13+/-11 normalized units (P<0.05), respectively. The change in cross-spectral alpha-index calculated as the square root of the ratio of RR interval power to systolic spectral power in the HF band (although not alpha-index calculated in the same way for the low-frequency bands or baroreflex sensitivity assessed by the phenylephrine bolus method) was attenuated with L-NMMA compared with phenylephrine (Delta=4+/-8 versus 14+/-15 ms/mm Hg, respectively; P<0.02) and with sodium nitroprusside compared with hydralazine (Delta=-7+/-6 and -9+/-7 ms/mm Hg, respectively; P<0.05). In conclusion, these data demonstrate that NO augments cardiac vagal control in humans.

Heart rate variability – a therapeutic target?

Reduced heart rate variability (HRV) is a powerful and independent predictor of an adverse prognosis in patients with heart disease and in the general population. The HRV is largely determined by vagally mediated beat to beat variability, conventionally known as respiratory sinus arrhythmia. Thus, HRV is primarily an indicator of cardiac vagal control. It is still unclear whether the relationship between measures of cardiac vagal control and mortality is causative or mere association. Possible mechanisms by which cardiac vagal activity might beneficially influence prognosis include a decrease in myocardial oxygen demand, a reduction in sympathetic activity and a decreased susceptibility of the ventricular myocardium to lethal arrhythmia. In animals, augmentation of cardiac vagal control by nerve stimulation or by drugs is associated with a reduction in sudden death in susceptible models. In humans a number of drugs which have been shown to reduce mortality and sudden death in large randomised trials can also be demonstrated to increase HRV. As a result of this evidence, it has been suggested that the effect of drugs or other therapeutic manoeuvres on HRV might be used to predict clinical efficacy. The use of HRV as a therapeutic target is discussed in this review.

The influence of small fibre muscle mechanoreceptors on the cardiac vagus in humans

We have previously shown that activation of muscle receptors by passive stretch (PS) increases heart rate (HR) with little change in blood pressure (BP). We proposed that PS selectively inhibits cardiac vagal activity. We attempted to test this by performing PS during experimental alterations in vagal tone. Large decreases in vagal tone were induced using either glycopyrrolate or mild rhythmic exercise. Milder alterations in vagal tone were achieved by altering carotid baroreceptor input: neck pressure (NP) or neck suction (NS). PS of the triceps surae was tested in 14 healthy human volunteers. BP, ECG and respiration were recorded. PS alone caused a significant decrease (P < 0.05) in R–R interval (962 ± 76 ms at baseline compared to 846 ± 151 ms with PS), and showed a reduction in HR variability, which was not significant. The decrease in R–R interval with PS was significantly less (P < 0.05, n= 3) following administration of glycopyrrolate (−8.1 ± 4.5 ms) compared to PS alone (−54 ± 11 ms), and also with PS during handgrip (+10 ± 10 ms) compared with PS alone (−74 ± 15 ms) (P < 0.05, n= 5). Milder reductions in vagal activity (NP) resulted in a small but insignificant further decrease in R–R interval in response to PS (−107 ± 17 ms compared to PS alone −96 ± 13 ms, n= 5). Mild increases in vagal activity (NS) during PS resulted in smaller decreases in R–R interval (−39 ± 5.5 ms) compared to PS alone (−86 ± 17 ms) (P < 0.05, n= 8). BP was not significantly changed by stretch in any tests. The results indicate that amongst muscle receptors there is a specific group activated by stretch that selectively inhibit cardiac vagal tone to produce tachycardia.

Standalone balloon aortic valvuloplasty: Indications and outcomes from the UK in the transcatheter valve era

We sought to characterize UK‐wide balloon aortic valvuloplasty (BAV) experience in the TAVI era.

Intralesional Abciximab and Thrombus Aspiration in Patients With Large Anterior Myocardial Infarction One-Year Results From the INFUSE-AMI Trial

Background—Whether intralesional abciximab administration and thrombus aspiration confer clinical benefits to patients undergoing primary percutaneous coronary intervention for ST-segment–elevation myocardial infarction is controversial. Methods and Results—A total of 452 patients with ST-segment–elevation myocardial infarction caused by proximal or mid left anterior descending artery occlusion undergoing primary percutaneous coronary intervention with bivalirudin anticoagulation were randomized in a 2×2 factorial design to bolus abciximab delivered locally at the infarct lesion site versus no abciximab and to manual thrombus aspiration versus no aspiration. Treatment with intralesional abciximab, thrombus aspiration, or both therapies compared with no active therapy before stent implantation resulted in lower 1-year rates of death (4.5% versus 10.4%; P=0.03), severe heart failure (4.2% versus 10.3%; P=0.02), and stent thrombosis (0.9% versus 3.8%; P=0.046). Between 30 days and 1 year of follow-up, treatment with intralesional abciximab compared with no abciximab was associated with a lower rate of death (1.4% versus 4.9%; P=0.04) and composite major adverse ischemic events (3.3% versus 7.8%; P=0.04), with nonsignificantly different overall 1-year rates of mortality, composite ischemic events, and heart failure–related events. Thrombus aspiration compared with no aspiration was associated with lower rates of new-onset severe heart failure between 30 days and 1 year (0.9% versus 4.5%; P=0.02) and of rehospitalization for heart failure from randomization to 1 year (0.9% versus 5.4%; P=0.0008), with nonsignificantly different rates of mortality. Conclusions—Intralesional abciximab and thrombus aspiration may have long-term benefits in patients with anterior ST-segment–elevation myocardial infarction presenting early after symptom onset and undergoing primary percutaneous coronary intervention with bivalirudin anticoagulation. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT00976521.

CoreValve transcatheter aortic valve implantation via the subclavian artery: comparison with the transfemoral approach.

To the Editor: Transcatheter aortic valve implantation (TAVI) has emerged as a promising alternative to surgical aortic valve replacement for patients with severe aortic stenosis considered to be at high operative risk. TAVI is most commonly performed via the femoral artery. However, the large-

Effects of nitroglycerin treatment on cardiac autonomic control in heart failure

There is substantial animal data suggesting that nitric oxide (NO) has an important role as a modulator of cardiac autonomic control with a net vagotonic and sympatholytic role. Recent human work would support this concept. This study investigated the effects of the NO donor glyceryl trinitrate (GTN) upon measures of cardiac vagal activity in heart failure. Twelve stable chronic heart failure patients were studied in a randomised double blind, placebo controlled crossover study to assess the effects of chronic treatment with transdermal GTN (10 mg per day) on heart rate variability (HRV) measures of cardiac vagal activity. No significant difference between GTN and placebo was observed in mean arterial blood pressure and most measures of HRV and baroreflex sensitivity (BRS). BRS measured by the alpha-LF index showed a small rise. In conclusion, chronic GTN administration does not produce a significant increase in HRV measures of cardiac vagal activity in patients with heart failure.

Chronotropic effects of nitric oxide in the denervated human heart

Nitric oxide synthase is expressed in the sino‐atrial node and animal data suggests a direct role for nitric oxide on pacemaker activity. Study of this mechanism in intact humans is complicated by both reflex and direct effects of nitric oxide on cardiac autonomic control. Thus, we have studied the direct effects of nitric oxide on heart rate in human cardiac transplant recipients who possess a denervated donor heart. In nine patients, the chronotropic effects of systemic injection of the nitric oxide synthase inhibitor NG‐monomethyl‐l‐arginine (l‐NMMA) (3 mg kg−1) or increasing bolus doses of the nitric oxide donor, sodium nitroprusside (SNP), were studied. Injection of l‐NMMA increased mean arterial pressure by 17 ± 2 mmHg (mean ±s.e.m.; P < 0.001) and also had a significant negative chronotropic effect, lengthening the R‐R interval by 54 ± 8 ms (P < 0.001). This bradycardia was not reflex in origin since injection of the non‐NO‐dependent vasoconstrictor, phenylephrine (100 μg) achieved a similar rise in mean arterial pressure (18 ± 3 mmHg; P < 0.001) but failed to change R‐R interval duration (ΔR‐R =−3 ± 4 ms). Furthermore, no change in levels of circulating adrenaline was observed with l‐NMMA. Conversely, injection of sodium nitroprusside resulted in a positive chronotropic effect with a dose‐dependent shortening of R‐R interval duration, peak ΔR‐R =−25 ± 8 ms with 130 μg (P < 0.01). These findings indicate that nitric oxide exerts a tonic, direct, positive chronotropic influence on the denervated human heart. This is consistent with the results of animal experiments showing that nitric oxide exerts a facilitatory influence on pacemaking currents in the sino‐atrial node.