The role of gender in resting full-cycle ratio (RFR) guided coronary revascularization.

BACKGROUND: Gender-based differences in clinical outcomes of patients undergoing fractional flow reserved (FFR) guided coronary revascularization is well documented. This study aimed to compare resting full-cycle ratio (RFR) values between men and women and whether this translated into difference in clinical outcomes in patients who underwent RFR-guided coronary revascularization. METHODS: This was a retrospective single-centre study of consecutive patients who underwent RFR-guided revascularization for coronary lesions with intermediate degree of stenosis. The primary endpoint was a composite of all-cause mortality, myocardial infarction (MI), unplanned revascularization, and unstable angina requiring hospital admission at one year. RESULTS: In 373 consecutive patients (510 lesions, 26% women) there was no statistically significant difference in RFR value between men and women (0.90 ±â€¯10 versus 0.90 ±â€¯11, P = 0.95). There was no statistically significant difference between men and women in the primary endpoint, even after adjustment to the imbalance between the two groups [3.7% vs. 3.0%; HR 1.43, 95% CI (0.46 to 4.43), P = 0.54]; or its individual components of death (1.1% vs 0.8%, P = 0.76), MI (1.9% vs 0.8%, P = 0.38) or unplanned revascularization, including unstable angina admissions (2.6% vs 2.3%, P = 0.82). The comparable clinical outcomes were consistent across all different subgroups, including clinical presentation, diabetes status, left ventricle systolic function, kidney function, and the interrogated coronary artery. CONCLUSION: Our study suggests no significant gender-based difference in the value of RFR or 1-year clinical outcomes in patients undergoing resting physiology guided coronary revascularization.

Very Early Discharge After Primary Percutaneous Coronary Intervention for ST-Elevation Myocardial Infarction: Mortality Outcomes at Six Months.

BACKGROUND: Current guidelines recommend that low risk patients presenting with ST-segment elevation myocardial infarction (STEMI) and undergoing uncomplicated primary percutaneous coronary intervention (PPCI) can be discharged home in 48-72 h. We report the safety of early discharge in STEMI patients undergoing uncomplicated PPCI after 24-h stay in-hospital. METHODS: We performed a retrospective analysis of prospectively collected data of consecutive patients presenting with STEMI between January 2014 and December 2020. One- and 6-month mortality rates were compared between patients who underwent next day (early discharge group) and two days in-hospital stay (standard discharge group). RESULTS: Of 6119 STEMI patients, 4033 were included in the analysis, of whom 1674 (42 %) underwent early discharge. Patients in the early discharge group were younger, more likely to be male, and had a lower peak troponin. Both groups had similar ischemia- and door-to-balloon time, but anterior STEMI were less frequent in the early discharge group. The 1- and 6-month mortality rate for the whole cohort was 0.6 % and 1.3 %, respectively. After adjustment, there were no significant differences in the 1-month [HR 0.54; 95 % CI (0.20 to 1.47), P = 0.23] and 6-month mortality [HR 0.73; 95 % CI (0.38 to 1.41), P = 0.35] between early and standard discharge groups. Age, admission heart rate and chronic obstructive lung disease were identified as independent predictors of 6-month mortality in patients who underwent early discharge strategy. CONCLUSION: Our data confirms safety of next day discharge of patients presenting with STEMI after successful PPCI and uncomplicated post-procedural course.

Isolated Septal Artery Infarction in a Cocaine User.

Septal branches arising from the left anterior descending coronary artery supply the anterior interventricular septum in unison. In this unusual presentation of cocaine heart disease, occlusion of a single dominant septal perforator caused a large septal myocardial infarction, resulting in significant left ventricular impairment.

Smoking status and mortality outcomes following percutaneous coronary intervention.

OBJECTIVE: The aim of this study was to assess the impact of smoking on short (30-day) and intermediate (30-day to 6-month) mortality following percutaneous coronary intervention (PCI). BACKGROUND: The effect of smoking on mortality post-PCI is lacking in the modern PCI era. METHODS: This was a retrospective analysis of prospectively collected data comparing short- and intermediate-term mortality amongst smokers, ex-smokers and non-smokers. RESULTS: The study cohort consisted of 12,656 patients: never-smokers (n = 4288), ex-smokers (n = 4806) and current smokers (n = 3562). The mean age (±standard deviation) was 57 (±11) years in current smokers compared with 67 (±11) in ex-smokers and 67 (±12) in never-smokers; p < 0.0001. PCI was performed for acute coronary syndrome (ACS) in 84.1% of current smokers, 57% of ex-smokers and 62.9% in never-smokers; p < 0.0001. In a logistic regression model, the adjusted odds ratios (95% confidence intervals (CIs)) for 30-day mortality were 1.60 (1.10-2.32) in current smokers and 0.98 (0.70-1.38) in ex-smokers compared with never-smokers. In the Cox proportional hazard model, the adjusted hazard ratios (95% CI) for mortality between 30 days and 6 months were 1.03 (0.65-1.65) in current smokers and 1.19 (0.84-1.67) in ex-smokers compared with never-smokers. CONCLUSION: This large observational study of non-selected patients demonstrates that ex-smokers and never-smokers are of similar age at first presentation to PCI, and there is no short- or intermediate-term mortality difference between them following PCI. Current smokers undergo PCI at a younger age, more often for ACS, and have higher short-term mortality. These findings underscore the public message on the benefits of smoking cessation and the harmful effects of smoking.

Effect of Pressure-controlled intermittent Coronary Sinus Occlusion (PiCSO) on infarct size in anterior STEMI: PiCSO in ACS study.

BACKGROUND: The aim of this clinical research was to investigate the effects of Pressure-controlled intermittent Coronary Sinus Occlusion (PiCSO) on infarct size at 5 days after primary percutaneous coronary intervention (pPCI) in patients with ST-segment elevation myocardial infarction (STEMI). METHODS AND RESULTS: This comparative study was carried out in four UK hospitals. Forty-five patients with anterior STEMI presenting within 12 h of symptom onset received pPCI plus PiCSO (initiated after reperfusion; n = 45) and were compared with a propensity score-matched control cohort from INFUSE-AMI (n = 80). Infarct size (% of LV mass, median [interquartile range]) measured by cardiac magnetic resonance (CMR) at day 5 was significantly lower in the PiCSO group (14.3% [95% CI 9.2-19.4%] vs. 21.2% [95% CI 18.0-24.4%]; p = 0.023). There were no major adverse cardiac events (MACE) related to the PiCSO intervention. CONCLUSIONS: PiCSO, as an adjunct to pPCI, was associated with a lower infarct size at 5 days after anterior STEMI in a propensity score-matched population.

Percutaneous coronary intervention for left main stem disease: Impact of diabetes mellitus on mortality.

OBJECTIVES: We assessed the impact of diabetes mellitus (DM) on mortality after percutaneous coronary intervention (PCI) for left main stem (LMS) disease. Second, we compared mortality outcomes between non-insulin treated (NITDM) and insulin treated diabetes (ITDM) in different clinical settings. BACKGROUND: There is a paucity of "real world" outcomes data in diabetic patients undergoing LMS PCI. METHODS: We undertook a retrospective analysis of consecutive patients undergoing unprotected LMS PCI at 2 high volume tertiary centers. Diabetic status and clinical setting for PCI were recorded. The primary outcome measure was all-cause 30-day and long-term mortality (up to 36 months) post index PCI. RESULTS: Between 2003 and 2017, 2,675 patients undergoing index LMS PCI were analyzed. Of those, 77.1% were non-DM, 15.8% NITDM, and 7.1% ITDM. Overall, DM status was not associated with higher 30-day mortality (OR 1.39, 95% CI 0.89-2.16, p = .15). During a median follow-up of 36 months, there was a borderline statistical association of DM with long-term mortality in all PCI settings (HR 1.31, 95% CI 1.00-1.71, p = .05). Compared to non-DM, ITDM but not NITDM was associated with short- and long-term mortality in all clinical presentations. CONCLUSIONS: Overall, DM did not impact on 30-day mortality and had only a borderline statistical association with long-term mortality. It did not have an influence on mortality in non-emergency LMS PCI. The impact of DM on mortality outcomes following LMS PCI was only significant in the insulin treated patients.

1-Year Outcomes of FFRCT-Guided Care in Patients With Suspected Coronary Disease: The PLATFORM Study.

BACKGROUND: Coronary computed tomographic angiography (CTA) plus estimation of fractional flow reserve using CTA (FFRCT) safely and effectively guides initial care over 90 days in patients with stable chest pain. Longer-term outcomes are unknown. OBJECTIVES: The study sought to determine the 1-year clinical, economic, and quality-of-life (QOL) outcomes of using FFRCT instead of usual care. METHODS: Consecutive patients with stable, new onset chest pain were managed by either usual testing (n = 287) or CTA (n = 297) with selective FFRCT (submitted in 201, analyzed in 177); 581 of 584 (99.5%) completed 1-year follow-up. Endpoints were adjudicated major adverse cardiac events (MACE) (death, myocardial infarction, unplanned revascularization), total medical costs, and QOL. RESULTS: Patients averaged 61 years of age with a mean 49% pre-test probability of coronary artery disease. At 1 year, MACE events were infrequent, with 2 in each arm of the planned invasive group and 1 in the planned noninvasive cohort (usual care strategy). In the planned invasive stratum, mean costs were 33% lower with CTA and selective FFRCT ($8,127 vs. $12,145 usual care; p < 0.0001); in the planned noninvasive stratum, mean costs did not differ when using an FFRCT cost weight of zero ($3,049 FFRCT vs. $2,579; p = 0.82), but were higher when using an FFRCT cost weight equal to CTA. QOL scores improved overall at 1 year (p < 0.001), with similar improvements in both groups, apart from the 5-item EuroQOL scale scores in the noninvasive stratum (mean change of 0.12 for FFRCT vs. 0.07 for usual care; p = 0.02). CONCLUSIONS: In patients with stable chest pain and planned invasive coronary angiography, care guided by CTA and selective FFRCT was associated with equivalent clinical outcomes and QOL, and lower costs, compared with usual care over 1-year follow-up. (The PLATFORM Study: Prospective LongitudinAl Trial of FFRct: Outcome and Resource IMpacts [PLATFORM]; NCT01943903).

Quality-of-Life and Economic Outcomes of Assessing Fractional Flow Reserve With Computed Tomography Angiography: PLATFORM.

BACKGROUND: Fractional flow reserve estimated using computed tomography (FFRCT) might improve evaluation of patients with chest pain. OBJECTIVES: The authors sought to determine the effect on cost and quality of life (QOL) of using FFRCT instead of usual care to evaluate stable patients with symptoms suspicious for coronary disease. METHODS: Symptomatic patients without known coronary disease were enrolled into 2 strata based on whether invasive or noninvasive diagnostic testing was planned. In each stratum, consecutive observational cohorts were evaluated with either usual care or FFRCT. The number of diagnostic tests, invasive procedures, hospitalizations, and medications during 90-day follow-up were multiplied by U.S. cost weights and summed to derive total medical costs. Changes in QOL from baseline to 90 days were assessed using the Seattle Angina Questionnaire, the EuroQOL, and a visual analog scale. RESULTS: In the 584 patients, 74% had atypical angina, and the pre-test probability of coronary disease was 49%. In the planned invasive stratum, mean costs were 32% lower among the FFRCT patients than among the usual care patients ($7,343 vs. $10,734 p < 0.0001). In the noninvasive stratum, mean costs were not significantly different between the FFRCT patients and the usual care patients ($2,679 vs. $2,137; p = 0.26). In a sensitivity analysis, when the cost weight of FFRCT was set to 7 times that of computed tomography angiography, the FFRCT group still had lower costs than the usual care group in the invasive testing stratum ($8,619 vs. $ 10,734; p < 0.0001), whereas in the noninvasive testing stratum, when the cost weight of FFRCT was set to one-half that of computed tomography angiography, the FFRCT group had higher costs than the usual care group ($2,766 vs. $2,137; p = 0.02). Each QOL score improved in the overall study population (p < 0.0001). In the noninvasive stratum, QOL scores improved more in FFRCT patients than in usual care patients: Seattle Angina Questionnaire 19.5 versus 11.4, p = 0.003; EuroQOL 0.08 versus 0.03, p = 0.002; and visual analog scale 4.1 versus 2.3, p = 0.82. In the invasive cohort, the improvements in QOL were similar in the FFRCT and usual care patients. CONCLUSIONS: An evaluation strategy based on FFRCT was associated with less resource use and lower costs within 90 days than evaluation with invasive coronary angiography. Evaluation with FFRCT was associated with greater improvement in quality of life than evaluation with usual noninvasive testing. (Prospective Longitudinal Trial of FFRCT: Outcomes and Resource Impacts [PLATFORM]; NCT01943903).

Rationale and design of the Prospective LongitudinAl Trial of FFRCT: Outcome and Resource IMpacts study.

BACKGROUND: Fractional flow reserve (FFR) measured by coronary computed tomography angiography (FFRCT) has been validated against invasive FFR. However, there are no data on how the use of FFRCT affects patient care and outcomes. The aim of this study is to compare standard practice guided by usual care testing to FFRCT-guided management in symptomatic subjects with suspected coronary artery disease (CAD). METHODS: In this prospective nonrandomized trial, symptomatic patients with suspected CAD will be enrolled in 2 consecutive cohorts: a usual care-guided pathway (cohort 1) and an FFRCT-guided pathway (cohort 2). Each cohort is divided into 2 groups according to whether noninvasive or invasive diagnostic testing was planned before enrollment. In all subjects, the patient's clinical team will review all diagnostic test results and determine a treatment strategy. A total sample size of 580 subjects will be enrolled and followed up for 12 months. RESULTS: The primary end point is the comparison of the percentage of patients with planned invasive testing who have a catheterization (invasive coronary angiography) within 90 days from initial assessment, which does not show a significant stenosis (defined as coronary artery stenosis >50% or invasive FFR ≤0.80). Secondary end points include the rate of invasive coronary angiography without obstructive CAD in those with planned noninvasive testing and, in all groups, noninferiority of resource use, quality of life, medical radiation exposure, and major adverse cardiac events up to 365 days of follow-up. CONCLUSIONS: The study compares clinical and economic outcomes based on diagnostic evaluation using FFRCT with that based on standard diagnostic strategies.

Clinical outcomes of fractional flow reserve by computed tomographic angiography-guided diagnostic strategies vs. usual care in patients with suspected coronary artery disease: the prospective longitudinal trial of FFR(CT): outcome and resource impacts study.

AIMS: In symptomatic patients with suspected coronary artery disease (CAD), computed tomographic angiography (CTA) improves patient selection for invasive coronary angiography (ICA) compared with functional testing. The impact of measuring fractional flow reserve by CTA (FFRCT) is unknown. METHODS AND RESULTS: At 11 sites, 584 patients with new onset chest pain were prospectively assigned to receive either usual testing (n = 287) or CTA/FFR(CT) (n = 297). Test interpretation and care decisions were made by the clinical care team. The primary endpoint was the percentage of those with planned ICA in whom no significant obstructive CAD (no stenosis ≥50% by core laboratory quantitative analysis or invasive FFR < 0.80) was found at ICA within 90 days. Secondary endpoints including death, myocardial infarction, and unplanned revascularization were independently and blindly adjudicated. Subjects averaged 61 ± 11 years of age, 40% were female, and the mean pre-test probability of obstructive CAD was 49 ± 17%. Among those with intended ICA (FFR(CT)-guided = 193; usual care = 187), no obstructive CAD was found at ICA in 24 (12%) in the CTA/FFR(CT) arm and 137 (73%) in the usual care arm (risk difference 61%, 95% confidence interval 53-69, P< 0.0001), with similar mean cumulative radiation exposure (9.9 vs. 9.4 mSv, P = 0.20). Invasive coronary angiography was cancelled in 61% after receiving CTA/FFR(CT) results. Among those with intended non-invasive testing, the rates of finding no obstructive CAD at ICA were 13% (CTA/FFR(CT)) and 6% (usual care; P = 0.95). Clinical event rates within 90 days were low in usual care and CTA/FFR(CT) arms. CONCLUSIONS: Computed tomographic angiography/fractional flow reserve by CTA was a feasible and safe alternative to ICA and was associated with a significantly lower rate of invasive angiography showing no obstructive CAD.

Differences in immune responses between CMV-seronegative and -seropositive patients with myocardial ischemia and reperfusion.

CMV infection is responsible for acceleration of immune senescence and linked to systemic pathologies, including cardiovascular diseases. In this study, we investigated differences in the immune response between CMV-seropositive and seronegative patients undergoing primary percutaneous coronary intervention (PPCI) for acute myocardial infarction (MI). Peripheral blood samples were taken at six different time points: pre-, 15, 30, 90 min, 24 h after PPCI and at 3 months after MI. Absolute counts of lymphocyte subpopulations, immune response to specific and nonspecific stimulation, serum cytokines and levels of CMV-IgG, cardiolipin-IgG, and anti-endothelial cell antibodies were assessed. CMV-seropositive patients with MI showed a twofold higher IFN-γ production to PHA-stimulation, up to 2.5-fold higher levels of IP-10 in serum and up to 30% lower serum levels of IL-16 compared to CMV-seronegative individuals. CMV-seropositive patients could be divided into two subgroups with high (IL-10Hi) and low (IL-10Lo) IL-10 serum levels during the acute stage of MI. The IL-10Hi CMV-seropositive subgroup showed an increased exit of late-differentiated T lymphocytes, NK and NKT-like cells from the circulation, which may potentially enhance cytotoxic damage in the ischemic myocardium. Finally, we did not observe an acceleration of autoimmunity by MI in CMV-seropositive individuals. The immune response during acute MI showed characteristic differences between CMV seronegative and seropositive patients, with a stronger pro-inflammatory response in seropositive patients. The effects of IP-10, IL-16, and IL-10 on characteristics of acute immune responses and formation of different immune profiles in CMV-seropositive individuals require further investigation.

Shock-index as a novel predictor of long-term outcome following primary percutaneous coronary intervention.

UNLABELLED: Early identification of higher risk patients presenting with ST-elevation myocardial infarction (STEMI) and undergoing primary percutaneous coronary intervention (PPCI) will allow a more aggressive strategy and approach. The aim of this study was to evaluate the shock index (ratio of heart rate/systolic blood pressure on admission) as a predictor of mortality post PPCI in addition to other parameters. METHODS: We analysed prospectively collected data on 3049 STEMI patients treated with PPCI in a large tertiary centre between March 2008-December 2011, out of which 2424 patients were aged up to 75 years (young) and 625 patients were older than 75 years (elderly). RESULTS: Compared to younger patients, in-hospital mortality rates were four-fold higher in the elderly (11.5% vs 2.8%, odds ratio (OR) 3.5, 95% confidence interval (CI) 2.0-5.9). Cardiogenic shock (OR 8.7 (5.1-14.6)), non-TIMI3 (Thrombosis In Myocardial Infarction) flow post percutaneous coronary intervention (PCI) (OR 5.0 (3.1-7.9)), age over 75 (OR 3.5 (2.3-5.3)) and a positive shock index pre PPCI (OR 3.5 (2.0-5.9)) were the strongest independent predictors of in-hospital mortality. For long-term outcome (median follow-up period 454 days) we excluded 141 (4.6%) patients that died during the initial hospital stay. Previous angina (hazard ratio (HR) 2.9), and previous cerebrovascular events (HR 3.7) were predictors of adverse outcome in the younger patients, while previous myocardial infarction (HR 2.0) and a positive shock index (HR 2.3) were predictors in the elderly. Cardiogenic shock prior to PPCI was not able to predict long-term outcome for in-hospital survivors. CONCLUSION: Mortality rates following PPCI were higher in elderly patients although remained acceptable. Invasively measured shock index before PPCI is the strongest independent predictor of long-term outcome in elderly patients. In addition, predictors of in-hospital mortality were similar across different age groups but differed significantly in relation to longer-term mortality.

Provision of gastroprotective medication and bleeding risk following acute coronary syndrome.

BACKGROUND: Gastrointestinal (GI) bleeding following percutaneous coronary intervention (PCI) is associated with increased mortality. ACCF/AHA/SCAI guidelines recommend prophylaxis to prevent GI bleeding in patients, with the highest GI bleeding risks taking dual-antiplatelet therapy (DAPT). The REPLACE risk score identifies factors predictive of peri-PCI bleeding from vascular access and non-access sites. We determined whether high bleeding risk acute coronary syndrome (ACS) patients taking DAPT were appropriately provided with GI prophylaxis and investigated the association between age and clinical presentation on the likelihood of receiving prophylactic therapy. METHODS: This is a retrospective analysis of all non-elective PCI patients at a single center between May and December 2008 stratified by age (<65, 65-74, and ≥ 75 years). REPLACE scores were calculated and discharge medication was obtained from case records. RESULTS: Complete discharge medication data were available for 800 patients (median age, 63 years; 45.1% with ST-elevation myocardial infarction [STEMI]). A total of 370 patients (46.3%) were high bleeding risk (REPLACE scores ≥ 10), including all patients ≥ 75 years (n = 173), 83.5% of patients 65-74 years (n = 177), and 4.8% of patients <65 years (n = 20). In total, 97.6% were discharged on DAPT. Within the high bleeding risk group, 45.1% received GI prophylaxis. Patients 65-74 years were least likely to receive prophylaxis (<65 years, 60%; 65-74 years, 38.4%; ≥ 75 years, 50.3%; P<.03). Presentation with STEMI was independently associated with a reduced likelihood of GI prophylaxis provision (odds ratio, 0.63; 95% confidence interval, 0.40-0.99; P=.045). CONCLUSIONS: Less than half of ACS patients at high bleeding risk taking DAPT are provided with GI prophylaxis. Increased use of objective bleeding risk scores may help guide risk/benefit decisions in patients taking clopidogrel and proton pump inhibitors.

Laser Doppler assessment of dermal circulatory changes in people with coronary artery disease.

BACKGROUND: Dermal microcirculation provides an easily accessible vasculature bed which can be used to assess endothelial mediated vasodilatation. We studied and compared microcirculatory changes in response to acetylcholine iontophoresis (ACh), local heating of the skin and reactive hyperaemia in patients with coronary artery disease (CAD). METHODS AND RESULTS: Forty eight patients with CAD were studied and compared with 25 age and sex matched control subjects. Vasodilatory changes in the dermal microcirculation were assessed in response to ACh iontophoresis, local heating of the skin and reactive hyperaemia using a laser Doppler flowmeter (LDF). RESULTS: Body mass index (BMI) and systolic BP were higher in people with CAD, (p=0.001, 0.043). The perfusion change (measured as absolute in agreement with our previous publish results) in response to ACh iontophoresis, local heating of the skin and reactive hyperaemia, in healthy controls was 234 (190-286), 90 (69-118), 139(106-172) arbitrary perfusion units (APU) compared to 161 (121-214), 50 (39-63), 116(77-143) APU in patients with CAD; p<0.03. The time to peak perfusion in response to reactive hyperaemia was significantly higher in patients with CAD, 14.1±4.0 vs 10.9±1.7s; p=0.001. There was a small but significant positive correlation between the perfusion change in response to ACh iontophoresis and local heating (r=0.31, p=0.035). On ROC curve analysis, perfusion changes with heating had higher sensitivity and specificity in discriminating patients with CAD from the healthy controls with an area under the curve (AUC) of 0.86, with a specificity of 92% and sensitivity of 77% compared to a perfusion changes by reactive hyperaemia, AUC of 0.68 (41% sensitivity and 91% specificity) and ACh iontophoresis, AUC of 0.76 (88% sensitivity and 60% specificity). CONCLUSION: Vasodilatation in the dermal microcirculation measured by the three techniques is attenuated in patients with coronary artery disease. Local heating of the skin is a better discriminator of patients with CAD than ACh iontophoresis and reactive hyperaemia.

Comparative reproducibility of dermal microvascular blood flow changes in response to acetylcholine iontophoresis, hyperthermia and reactive hyperaemia.

Laser Doppler fluxmetry (LDF) can non-invasively measure skin microvascular changes in response to acetylcholine (ACh), local heating of the skin and reactive hyperaemia following arterial occlusion. Various studies have used microvascular changes in response to these stimuli, especially ACh iontophoresis and local heating, as a surrogate marker of endothelial function. There are few data in the literature regarding the comparative reproducibility of microvascular perfusion changes induced by the three stimuli. The aim of this study was to systematically assess and compare the reproducibility of skin microcirculatory function in response to each of these challenges. Ten healthy non-smoking subjects (seven males) median age 36 years (range 23-46), with no history of hypertension, diabetes, coronary artery disease or any connective tissue disorder, were studied. Changes in skin microcirculation in response to ACh iontophoresis, local heating of the skin and post-occlusive reactive hyperaemia, on two separate days (median 31, range 11-42 days), were assessed in all subjects. We measured three parameters: the change in perfusion from baseline perfusion (peak minus baseline perfusion), the relative percentage change in perfusion from baseline (peak--baseline)/baseline x 100 (%) and also the time-to-peak perfusion. The reproducibility of the change in perfusion had coefficients of variation (CV) of 9.3% for local skin heating, 19.4% for reactive hyperaemia and 25.5% for ACh iontophoresis. The relative percentage change in perfusion from baseline was more variable with CVs ranging from 23% to 39%. The coefficient of variation of time-to-peak perfusion was 7.0% for heating, 15.1% for reactive hyperaemia and 10.4% for ACh iontophoresis. We have shown that microcirculatory changes measured by the change in perfusion from baseline and time-to-peak perfusion in response to ACh, post-occlusive reactive hyperaemia and local skin heating had good reproducibility when carried out in a controlled environment with a standardized protocol. Relative change in perfusion had relatively poor reproducibility. The change in perfusion and time-to-peak perfusion for local skin heating were the most reproducible overall.

Malignancy: an unrecognized risk factor for coronary stent thrombosis?

Stent thrombosis is a potentially catastrophic complication of coronary artery stenting. There have been particular concerns about the incidence of stent thrombosis following insertion of drug-eluting stents. We report a series of cases in which stent thrombosis occurred in association with malignancy and describe the potential mechanisms behind such an association. We speculate that this association merits further investigation as it raises the possibility that known malignancy may be a risk factor for stent thrombosis and that unexplained stent thrombosis, particularly if recurrent, should stimulate a search for occult malignancy.

The Dix-Hallpike test and the canalith repositioning maneuver.

The Dix-Hallpike test and the canalith repositioning maneuver (CRM) are used to diagnose and treat benign positional vertigo (BPV). Dix-Hallpike is the standard procedure for diagnosis of BPV, but if the horizontal canal is not tested for BPV and the Dix-Hallpike is only carried out once, the condition may not be diagnosed and appropriately treated. We describe our method of testing for BPV and treating it with CRM. The Dix-Hallpike test involves rapidly moving the patient from a sitting position to "head hanging," where the patient's head is at least 10 degrees below horizontal. This is performed initially for the posterior semicircular canals. If these movements fail to elicit vertigo and nystagmus, tests of the horizontal semicircular canals are performed by laying the patient on each side. Importantly, if there is no vertigo or nystagmus elicited by testing the horizontal semi-circular canals, the posterior semicircular canals are tested again. It appears that being held in the head hanging positions and then left and right lateral positions will often allow the canaliths to collect such that the Dix-Hallpike test will become positive. Failure to repeat the tests of the posterior semicircular canals may result in a falsely negative test. Testing the horizontal canals and repeating the Dix-Hallpike test will reduce the likelihood of patients undergoing extra testing or other consequences of misdiagnosis. If, during any of this testing, a movement elicits vertigo or nystagmus, the appropriate CRM is then carried out.

Central projections of the saccular and utricular nerves in macaques.

The central projections of the utricular and saccular nerve in macaques were examined using transganglionic labeling of vestibular afferent neurons. In these experiments, biotinylated dextran amine was injected directly into the saccular or utricular neuroepithelium of fascicularis (Macaca fascicularis) or rhesus (Macaca mulatta) monkeys. Two to 5 weeks later, the animals were killed and the peripheral vestibular sensory organs, brainstem, and cerebellum were collected for analysis. The principal brainstem areas of saccular nerve termination were lateral, particularly the spinal vestibular nucleus, the lateral portion of the superior vestibular nucleus, ventral nucleus y, the external cuneate nucleus, and cell group l. The principal cerebellar projection was to the uvula with a less dense projection to the nodulus. Principle brainstem areas of termination of the utricular nerve were the lateral/dorsal medial vestibular nucleus, ventral and lateral portions of the superior vestibular nucleus, and rostral portion of the spinal vestibular nucleus. In the cerebellum, a strong projection was observed to the nodulus and weak projections were present in the flocculus, ventral paraflocculus, bilateral fastigial nuclei, and uvula. Although there is extensive overlap of saccular and utricular projections, saccular inputs to the lateral portions of the vestibular nuclear complex suggest that saccular afferents contribute to the vestibulospinal system. In contrast, the utricular nerve projects more rostrally into areas of known concentration of vestibulo-ocular related cells. Although sparse, the projections of the utricle to the flocculus/ventral paraflocculus suggest a potential convergence with floccular projection inputs from the vestibular brainstem that have been implicated in vestibulo-ocular motor learning.