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Objective To assess safety and feasibility of autologous adipose-derived regenerative cells (ADRCs), for treatment of chronic ischemic cardiomyopathy patients. Background Preclinical and early clinical trials suggest ADRCs have excellent potential for ischemic conditions. Methods The Athena program consisted of two parallel, prospective, randomized (2:1, active: placebo), double-blind trials assessing intramyocardial (IM) ADRC delivery [40-million, n = 28 (ATHENA) and 80-million (ATHENA II) cells, n = 3]). Patients with an EF ≥20% but ≤45%, multivessel coronary artery disease (CAD) not amenable to revascularization, inducible ischemia, and symptoms of either angina (CCS II–IV) or heart failure (NYHA Class II–III) on maximal medical therapy were enrolled. All patients underwent fat harvest procedure (≤450 mL adipose), on-site cell processing (Celution® System, Cytori Therapeutics), electromechanical mapping, and IM delivery of ADRCs or placebo. Results Enrollment was terminated prematurely due to non-ADRC-related adverse events and subsequent prolonged enrollment time. Thirty-one patients (17-ADRCs, 14-placebo) mean age 65 ± 8 years, baseline LVEF(%) 31.1 ± 8.7 (ADRC), 31.8 ± 7.7 (placebo) were enrolled. Change in V02 max favored ADRCs (+45.4 ± 222 vs. −9.5 ± 137 mL/min) but there was no difference in left ventricular function or volumes. At 12-months, heart failure hospitalizations occurred in 2/17 (11.7%) [ADRC] and 3/14 (21.4%) [placebo]. Differences in NYHA and CCS classes favored ADRCs at 12-months with significant improvement in MLHFQ (−21.6 + 13.9 vs. −5.5 + 23.8, P = 0.038). Conclusions A small volume fat harvest, automated local processing, and IM delivery of autologous ADRCs is feasible with suggestion of benefit in “no option” CAD patients. Although the sample size is limited, the findings support feasibility and scalability for treatment of ischemic cardiomyopathy with ADRCs. © 2016 Wiley Periodicals, Inc.

Background— Less than one-third of smokers hospitalized with an acute coronary syndrome (ACS) remain abstinent following discharge. We assessed whether varenicline, begun in-hospital, is efficacious for smoking cessation following ACS. Methods and Results— We conducted a multi-center, double-blind, randomized, placebo-controlled trial in which smokers hospitalized with an ACS were randomized to varenicline or placebo for 12 weeks. All patients received low-intensity counseling. The primary end point was point-prevalence smoking abstinence assessed at 24 weeks by 7-day recall and biochemical validation using expired carbon monoxide. A total of 302 patients were randomized (mean age 55±9 years; 75% male; 56% ST-segment elevation myocardial infarction; 38% non-ST-segment elevation myocardial infarction; 6% unstable angina). Patients smoked a mean of 21±11 cigarettes/d at the time of hospitalization and had been smoking for a mean of 36±12 years. At 24 weeks, patients randomized to varenicline had significantly higher rates of smoking abstinence and reduction than patients randomized to placebo. Point-prevalence abstinence rates were 47.3% in the varenicline group and 32.5% in the placebo group ( P =0.012; number needed to treat=6.8). Continuous abstinence rates were 35.8% and 25.8%, respectively ( P =0.081; number needed to treat=10.0), and rates of reduction ≥50% in daily cigarette consumption were 67.4% and 55.6%, respectively ( P =0.05; number needed to treat=8.5). Adverse event rates within 30 days of study drug discontinuation were similar between groups (serious adverse events: varenicline 11.9%, placebo 11.3%; major adverse cardiovascular events: varenicline 4.0%, placebo 4.6%). Conclusions— Varenicline, initiated in-hospital following ACS, is efficacious for smoking cessation. Future studies are needed to establish safety in these patients. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00794573.

BACKGROUND: Patients who continue to smoke after acute coronary syndrome are at increased risk of reinfarction and death. We previously found use of varenicline to increase abstinence 24 weeks after acute coronary syndrome; here we report results through 52 weeks. METHODS: The EVITA trial was a multicentre, double-blind, randomized, placebo-controlled trial of varenicline for smoking cessation in patients admitted to hospital with acute coronary syndrome. Participants were randomly assigned (1:1) to receive varenicline or placebo for 12 weeks, in conjunction with low-intensity counselling. Smoking abstinence was assessed via 7-day recall, with biochemical validation using exhaled carbon monoxide. Participants lost to follow-up or withdrawn were assumed to have returned to smoking. RESULTS: Among the 302 participants, abstinence declined over the course of the trial, with 34.4% abstinent 52 weeks after acute coronary syndrome. Compared with placebo, point estimates suggest use of varenicline increased point-prevalence abstinence (39.9% v. 29.1%, difference 10.7%, 95% confidence interval [CI] 0.01% to 21.44%; number needed to treat 10), continuous abstinence (31.1% v. 21.2%, difference 9.9%, 95% CI −0.01% to 19.8%) and reduction in daily cigarette smoking by 50% or greater (57.8% v. 49.7%, difference 8.1%, 95% CI −3.1% to 19.4%). Varenicline and placebo groups had similar occurrence of serious adverse events (24.5% v. 21.9%, risk difference 2.7%, 95% CI −7.3% to 12.6%) and major adverse cardiovascular events (8.6% v. 9.3%, risk difference −0.7%, 95% CI −7.8% to 6.5%). INTERPRETATION: Varenicline was efficacious for smoking cessation in this high-risk patient population. However, 60% of patients who received treatment with varenicline still returned to smoking. Trial registration: ClinicalTrials.gov, no. NCT00794573

BACKGROUND The RightLevelpH indicator is a new device designed to measure the pH of gastric aspirate obtained via a nasogastric tube while minimizing exposure of the operator. OBJECTIVE To validate the RightLevelpH indicator in vivo and in vitro. METHODS With general anesthesia, 20 patients had placement of a nasogastric tube and a gastric pH electrode catheter after endotracheal intubation. Direct intragastric pH was recorded simultaneously with gastric aspirate pH by using the RightLevelpH indicator and by using an external pH electrode. Measurements were made every 30 minutes until removal of the nasogastric tube as indicated clinically. In vitro validation of the RightLevelpH indicator was performed by using standard buffer solutions. RESULTS The pH of clear buffer solutions was linearly related to pH determined by the RightLevelpH indicator (R(2) = 0.99; P < .001). The pH of gastric aspirate determined with an external pH electrode was linearly related to the gastric aspirate pH determined by using the RightLevelpH indicator (R(2) = 0.92; P < .001). Intragastric pH determined with the catheter electrode was also linearly related but more loosely correlated with gastric aspirate pH determined by using an external pH electrode (R(2) = 0.52; P < .001) and by the RightLevelpH indicator (R(2) = 0.55; P < .001). CONCLUSIONS The RightLevelpH indicator provides accurate measurements of the pH of gastric aspirate in patients.

Background Smoking cessation and weight management are recommended after acute coronary syndrome ( ACS ); however, little is known about the effects of smoking cessation on weight change after ACS . We aimed to assess the effect of smoking cessation after ACS on weight over a 12‐month follow‐up period. Methods and Results Data were prospectively collected from the EVITA (Evaluation of Varenicline in Smoking Cessation for Patients Post‐Acute Coronary Syndrome) trial. Weight change was compared among 3 groups of patients: those who were completely abstinent (n=70), those who smoked intermittently (n=68), and those who smoked persistently (n=34). Patients' mean baseline weight was 83.9 kg ( SD 17.7) with a mean body mass index of 28.5 ( SD 5.4). Patients smoked a mean of 37.7 years ( SD 17.7) and a mean of 21.0 cigarettes ( SD 9.0) per day prior to their ACS . Weight change varied across groups, with abstainers gaining a mean of 4.8 kg ( SD 8.6), intermittent smokers gaining a mean of 2.0 kg ( SD 8.9) and persistent smokers losing a mean of 0.7 kg ( SD 7.4). At 52 weeks, abstainers were more likely to gain weight than persistent smokers (difference in means 5.5 kg; 95% CI 2.3–8.8). This weight gain was not associated with an increase in the use of antihypertensive or antidiabetic medications. Conclusions Following an ACS , significant weight is gained by patients who quit smoking. Weight‐management interventions among smokers who quit after ACS should be a focus of investigation in future research so that the cardiovascular benefits achieved by smoking cessation are not offset by weight gain in this high‐risk population. Clinical Trial Registration URL : http://www.clinicaltrials.gov . Unique identifier: NCT 00794573.

To assess safety and feasibility of autologous adipose-derived regenerative cells (ADRCs), for treatment of chronic ischemic cardiomyopathy patients.Preclinical and early clinical trials suggest ADRCs have excellent potential for ischemic conditions.The Athena program consisted of two parallel, prospective, randomized (2:1, active: placebo), double-blind trials assessing intramyocardial (IM) ADRC delivery [40-million, n = 28 (ATHENA) and 80-million (ATHENA II) cells, n = 3]). Patients with an EF ≥20% but ≤45%, multivessel coronary artery disease (CAD) not amenable to revascularization, inducible ischemia, and symptoms of either angina (CCS II-IV) or heart failure (NYHA Class II-III) on maximal medical therapy were enrolled. All patients underwent fat harvest procedure (≤450 mL adipose), on-site cell processing (Celution® System, Cytori Therapeutics), electromechanical mapping, and IM delivery of ADRCs or placebo.Enrollment was terminated prematurely due to non-ADRC-related adverse events and subsequent prolonged enrollment time. Thirty-one patients (17-ADRCs, 14-placebo) mean age 65 ± 8 years, baseline LVEF(%) 31.1 ± 8.7 (ADRC), 31.8 ± 7.7 (placebo) were enrolled. Change in V0A small volume fat harvest, automated local processing, and IM delivery of autologous ADRCs is feasible with suggestion of benefit in "no option" CAD patients. Although the sample size is limited, the findings support feasibility and scalability for treatment of ischemic cardiomyopathy with ADRCs. © 2016 Wiley Periodicals, Inc.

Due to the changing population in patients with myocardial infarction, recruiting patients in clinical trials continues to challenge clinical investigators. The Cardiovascular Cell Therapy Research Network (CCTRN) chose to expand the reach and power of its recruitment effort by incorporating both referral and treatment satellite centers. Eight treatment satellites were successfully identified and they screened patients over a two year period. The result of this effort was an increase in recruitment, with these treatment satellites contributing 30 percent of the patients to two of the three Network studies. The hurdles these satellite treatment centers faced and how they surmounted them provide instruction to clinical research groups eager to expand to satellite systems and to health care practitioners who are interested in taking part in multicenter clinical trials.

Considerable experimental and clinical data indicate that sex has an important influence on cardiovascular physiology and pathology. This report integrates selected literature with new data from the Women's Ischemia Syndrome Evaluation (WISE) on vascular findings in women with ischemic heart disease (IHD) and how these findings differ from those in men. A number of common vascular disease-related conditions are either unique to (e.g., hypertensive disorders of pregnancy, gestational diabetes, peripartum dissection, polycystic ovarian syndrome, etc.) or more frequent (e.g., migraine, coronary spasm, lupus, vasculitis, Raynaud's phenomenon, etc.) in women than men. Post-menopausal women more frequently have many traditional vascular disease risk conditions (e.g., hypertension, diabetes, obesity, inactivity, and so on), and these conditions cluster more frequently in them than men. Considerable evidence supports the notion that, with these requisite conditions, women develop a more severe or somewhat different form of vascular disease than men. Structurally, women's coronary vessels are smaller in size and appear to contain more diffuse atherosclerosis, their aortas are stiffer (fibrosis, remodeling, and so on), and their microvessels appear to be more frequently dysfunctional compared with men. Functionally, women's vessels frequently show impaired vasodilator responses. Limitations of existing data and higher risks in women with acute myocardial infarction, need for revascularization, or heart failure create uncertainty about management. A better understanding of these findings should provide direction for new algorithms to improve management of the vasculopathy underlying IHD in women.

Background— Sirolimus-eluting stents (SESs) reduce angiographic restenosis in patients with focal, native coronary artery stenoses. This study evaluated the usefulness of SESs in complex native-vessel lesions at high risk for restenosis. Methods and Results— Angiographic follow-up at 240 days was obtained in 701 patients with long (15- to 25-mm) lesions in small-diameter (2.5- to 3.5-mm) native vessels who were randomly assigned to treatment with SESs or bare-metal stents (BMSs) in the SIRIUS trial. Quantitative angiographic measurements of minimal lumen diameter and percent diameter stenosis were obtained within the treated segment, within the stent, and within its 5-mm proximal and distal edges. Patients treated with SESs had lower rates of binary (>50% diameter stenosis) angiographic restenosis within the segment (8.9% versus 36.3% with the BMS; P P P Conclusions— Compared with BMSs, SESs reduced angiographic late lumen loss within the stent and its adjacent 5-mm margins in patients with complex native-vessel lesions.

To understand the role of bone marrow mononuclear cells in the treatment of acute myocardial infarction, this overview offers a retrospective examination of strengths and limitations of 3 contemporaneous trials with attention to critical design features and provides an analysis of the combined data set and implications for future directions in cell therapy for acute myocardial infarction.

A new vascular sheath design (anesthesia infusion sleeve or AIS) was developed to enable administration of local anesthetics or other medications into the subcutaneous tissue around the insertion site without any additional needle sticks or other manipulation. Design of the system was based upon anatomic measurements of femoral artery depth in 150 patients. Animal studies of prototypes verified subcutaneous delivery using both radiographic methods and direct dissection. The pharmacokinetic profile of plasma lidocaine was also studied in three pigs to document subcutaneous delivery with the AIS. Subsequently a clinical trial of the AIS versus a standard sheath was done in 20 patients undergoing coronary angioplasty. Pain associated with sheath removal was graded using a verbal scale at baseline, during infiltration of the area, and at 1-min intervals during compression for 15 min. Baseline pain was identical in both groups, whereas, during infiltration with lidocaine, pain increased in the standard sheath group and decreased in the AIS group. Pain increased slightly in both groups with initial compression; however, it was significantly less in the AIS group. This difference persisted for several minutes after initial compression. The AIS represents a simple addition to standard sheath protocol offering superior pain control compared to standard technique for sheath removal without the need for systemic analgesics or other medications.

Substantial weight loss in morbidly obese subjects produces improvement in LV diastolic filling that is associated with weight loss-related decreases in LV mass and favorable alterations in LV loading conditions.

To identify factors influencing left ventricular (LV) diastolic filling in patients with morbid obesity, we performed transthoracic and Doppler echocardiography on 50 subjects whose actual body weight was ≥twice their ideal body weight and on 50 normal lean control subjects. The transmitral Doppler EA ratio and E wave deceleration half-time were used to assess LV diastolic filling. Significant negative correlations were seen between the EA ratio and the LV internal dimension in diastole ( r = 0.819, p = 0.0001), systolic blood pressure ( r = 0.751, p = 0.0001), LV end-systolic wall stress ( r = 0.782, p = 0.0001), and LV mass/height index ( r = 0.901, p = 0.0001). Significant positive correlations were seen between the E wave deceleration half-time and the LV internal dimension in diastole ( r = 0.743, p = 0.0001), systolic blood pressure ( r = 0.789, p = 0.0001), LV end-systolic wall stress ( r = 0.828, p = 0.0001), and LV mass/height index ( r = 0.831, p = 0.0001). No correlation was seen between diastolic blood pressure and either index of LV diastolic filling. Thus increasing LV mass is associated with progressive impairment of LV diastolic filling in morbidly obese individuals. The aforementioned alterations in LV loading conditions may contribute to impairment of LV diastolic filling directly or by increasing LV mass.

This study was designed to compare a new investigational coronary perfusion balloon (Wave, Scimed Life Systems Inc.) with that of an approved, widely used, current generation device (Flowtrack 40, Advanced Cardiovascular Systems). Domestic swine were anesthetized with pentobarbital and instrumented using standard percutaneous technique. Left ventricular contractile function (dP/dt) was monitored using a micromanometer while intracoronary and surface ECGs were also recorded. Eight target vessels were studied (4 LAD and 4 Cx) in random order. The perfusion balloons were kept inflated for 10 min. Complete coronary occlusion with a standard angioplasty balloon produced marked decreases in mean aortic pressure, left ventricular developed pressure, peak + dP/dt, peak -dP/dt, and significant ST segment elevation in both intracoronary and surface ECG at 30 seconds. Neither the Wave or Flowtrack 40 produced any change in heart rate or mean aortic pressure. Both catheters caused a drop in left ventricular developed pressure immediately after balloon inflation. At 10 min, however, there was a small but significant decrease only with the Flowtrack 40. Similarly, peak + dP/dt was slightly depressed during Flowtrack 40 inflation at 10 min but not with the Wave catheter. Both catheters produced ST segment elevation on the surface and intracoronary electrocardiographic records. These changes were significantly greater with the Flowtrack 40 system. Thus, both the Flowtrack 40 and Wave perfusion balloons are effective in preventing ischemia during coronary occlusion in swine; however, the latter system may be more effective in this model. © 1995 Wiley-Liss, Inc.

Item does not contain fulltext BACKGROUND: The effect of intensified platelet inhibition for patients with unstable angina or myocardial infarction without ST-segment elevation who do not undergo revascularization has not been delineated. METHODS: In this double-blind, randomized trial, in a primary analysis involving 7243 patients under the age of 75 years receiving aspirin, we evaluated up to 30 months of treatment with prasugrel (10 mg daily) versus clopidogrel (75 mg daily). In a secondary analysis involving 2083 patients 75 years of age or older, we evaluated 5 mg of prasugrel versus 75 mg of clopidogrel. RESULTS: At a median follow-up of 17 months, the primary end point of death from cardiovascular causes, myocardial infarction, or stroke among patients under the age of 75 years occurred in 13.9% of the prasugrel group and 16.0% of the clopidogrel group (hazard ratio in the prasugrel group, 0.91; 95% confidence interval [CI], 0.79 to 1.05; P=0.21). Similar results were observed in the overall population. The prespecified analysis of multiple recurrent ischemic events (all components of the primary end point) suggested a lower risk for prasugrel among patients under the age of 75 years (hazard ratio, 0.85; 95% CI, 0.72 to 1.00; P=0.04). Rates of severe and intracranial bleeding were similar in the two groups in all age groups. There was no significant between-group difference in the frequency of nonhemorrhagic serious adverse events, except for a higher frequency of heart failure in the clopidogrel group. CONCLUSIONS: Among patients with unstable angina or myocardial infarction without ST-segment elevation, prasugrel did not significantly reduce the frequency of the primary end point, as compared with clopidogrel, and similar risks of bleeding were observed. (Funded by Eli Lilly and Daiichi Sankyo; TRILOGY ACS ClinicalTrials.gov number, NCT00699998.).

Background The porous (Wolinski) balloon was designed to allow local delivery of compounds targeted to inhibit postintervention restenosis; however, successful use of the device has been hampered by arterial trauma caused by the balloon itself. This study utilized several experimental systems to assess the functional characteristics of the porous balloon catheter. This information was utilized to design and test a new microporous infusion catheter for local intra-arterial drug delivery. Methods Flow characteristics in fluid and semisolid media as well as arterial trauma by light and electron microscopy were documented for the porous and microporous balloons. In addition, the efficacy of methylene blue delivery in situ and in vitro was documented and quantified for the microporous design. Results The porous balloon exhibits flow characteristics consistent with orifice-related streaming that produces arterial trauma. By maximizing external balloon-pore density and minimizing pore size, the microporous design minimizes streaming in test systems. This is manifested by minimal arterial trauma when applied to intact arteries. The microporous catheter is effective for dye delivery both in situ and in vivo. Conclusions The microporous catheter design offers improved functional characteristics when compared with the porous balloon for local intra-arterial drug delivery.

Intravenous, sublingual, or aerosolized nitroglycerin was administered to 19 patients with coronary artery disease during clinically indicated cardiac catheterization. Eight blood samples were collected over 15 min from each patient, and analyzed for content of nitroglycerin, 1,2-glycerol dinitrate, and 1,3-glycerol dinitrate. Simultaneously, heart rate (HR), systolic blood pressure (SBP), and left ventricular end-diastolic pressure (LVEDP) were recorded. Plasma concentrations of nitroglycerin were highest after intravenous injection and lowest after sublingual tablets. Metabolite concentrations were highest after intravenous injection at early time-points; at later time-points, no between-group differences could be detected. SBP was minimally affected by intravenous nitroglycerin but was significantly reduced by sublingual and aerosolized formulations. Minor fluctuations in HR were observed in association with all three formulations. LVEDP was reduced by all three formulations of nitroglycerin but most rapidly by the intravenous form. Overall, no differences were detected in hemodynamic responses caused by sublingual and aerosolized nitroglycerin. Efficacy of sublingual and aerosolized nitroglycerin in patients undergoing cardiac catheterization is equivalent.

Heart rate and blood pressure were measured, and echocardiography was performed in 39 patients whose actual body weight was greater than twice their ideal body weight to identify factors influencing left ventricular (LV) systolic function in morbidly obese patients and assess the effect of weight loss on LV systolic function. Patients were studied before and after weight loss induced by gastroplasty. The study cohort was 133 +/- 8% overweight before weight loss and 39 +/- 7% overweight at the nadir of weight loss. Before weight loss, LV fractional shortening varied inversely with LV internal dimension in diastole (an indirect index of preload), LV end-systolic wall stress and systolic blood pressure (indexes of afterload). The weight loss-induced change in LV fractional shortening varied directly with the pre-weight loss LV internal dimension in diastole, LV end-systolic wall stress and systolic blood pressure, and inversely with the pre-weight loss LV fractional shortening. The weight loss-induced change in LV fractional shortening varied inversely with the weight loss-induced changes in LV end-systolic stress and systolic blood pressure. In patients with reduced LV fractional shortening (n = 14), weight loss produced a significant increase in LV fractional shortening that was accompanied by a significant decrease in LV internal dimension in diastole, LV end-systolic stress and systolic blood pressure. The results suggest that LV loading conditions have an important role in determining LV systolic function in morbidly obese patients. Improvement in LV systolic function in these patients is closely related to weight loss-induced alterations in LV loading conditions.

The pathophysiology of stable angina is discussed with respect to anatomic substrate, coronary and systemic hemodynamic mechanisms, the dynamic nature of coronary artery stenoses, and determinants of myocardial oxygen consumption. Cellular mechanisms involved in ischemia and the transduction of these changes into angina are also reviewed.

Both affiliation with an academic medical center and implementation of service line management may be effective management strategies for community health care organizations. The authors describe the design, implementation, and performance of a unique combination of these two distinct strategies for cardiovascular program development in the affiliation of the University of Florida Health Science Center with Health First, a regional community-based integrated delivery system.

The preceding chapter in this volume has addressed several different technologies which have been developed for localized delivery of bioactive substances to vascular segments. Although some overlap is inevitable, our focus shall be more general, with reference to specific catheters or devices when needed to illustrate problems and principles we have found to be important in evaluating transcatheter site-specific therapy in our laboratories. At the present time, three devices have been approved by the FDA for intraluminal drug administration which were actually developed with intramural drug delivery in mind. These devices are being used for intramural therapy both in the US and in other countries with very limited animal investigation to guide optimal clinical application Intramural sitespecific therapy is a relatively old idea in the laboratory but a new idea in the clinical arena. Local delivery in the coronary arteries may be useful for therapy of restenosis, in situ thrombosis, stent thrombosis, prevention of atherosclerosis, modification of coronary artery spasm, induction of angiogenesis and other applications as well. Nevertheless, very few published data are available regarding the basic functionality of catheter and non-catheter delivery systems. Efficiencies cf these systems for acute delivery and retention of marker substances is very low and certain systems have the potential to induce arterial trauma which may not only lead to acute clinical problems but also exacerbate the proliferative response to injury targeted by local therapy in the first place. In this chapter we hope to outline our approach to some of these issues which may aid in understanding the efficacy or lack thereof for certain catheter systems and which also may be useful in guiding new designs. Our primary focus shall be application of catheters using hydraulic delivery mechanisms or diffusion in the coronary circulation, however, the principles involved are applicable to arterial delivery in general.

A new vascular sheath design (anesthesia infusion sleeve, or AIS) was developed to enable administration of local anesthetics or other medications into the subcutaneous tissue around an arterial or venous insertion site without any additional needle sticks or manipulation. Design, animal testing, and an initial small single-site clinical study have previously been published. The current study was multicenter and randomized 80 patients to use of a standard sheath for vascular access or the AIS. Pain associated with sheath placement, postprocedure pain, and pain associated with sheath removal before and during manual compression was recorded. Baseline pain was identical in both the standard and AIS groups. Pain during infiltration and with initial femoral artery compression was significantly lower in the AIS group. A quality of life questionnaire indicated that the AIS sheath was associated with less discomfort and was preferred over a standard sheath in patients who had had a previous procedure performed. The AIS represents a simple addition to standard sheath design, offering superior pain control during removal compared to the standard technique, without the need for systemic analgesics or additional needle punctures.

BACKGROUND AND HYPOTHESIS Carbon dioxide is currently used as an arterial and venous contrast agent; however, little is known of its effects on left ventricular function. This study was undertaken to investigate those effects. METHODS Ascending doses of 5, 10, and 20 ml of carbon dioxide were administered into the left main coronary artery of domestic swine with and without a continuous infusion of intravenous nitroglycerin (50 micrograms/min). RESULTS Carbon dioxide had an immediate and profound depressant effect on both systolic and diastolic left ventricular function associated with ischemic electrocardiographic changes. Compared with controls (% change), ascending doses of carbon dioxide decreased systolic pressure by -35 +/- 7, -48 +/- 8, and -53 +/- 4 in the absence of nitroglycerin, and by -32 +/- 9, -50 +/- 9, and -60 +/- 9 in the presence of nitroglycerin. Peak+dP/dt decreased by -54 +/- 7, -61 +/- 11, and -64 +/- 3 in the absence of nitroglycerin, and by -36 +/- 13, -55 +/- 11, and -65 +/- 11 in the presence of nitroglycerin. Minimum -dP/dt increased by 65 +/- 8,71 +/- 8, and 77 +/- 3 in the absence of nitroglycerin, and by 63 +/- 7,71 +/- 8, and 78 +/- 7 in the presence of nitroglycerin. No significant changes in heart rate were observed; however, widespread ST-segment elevation was observed in all animals. Coronary angiography following carbon dioxide injection revealed a marked decrease in coronary flow velocity until the gas was cleared from the microcirculation. This was also documented by direct measurement of flow velocity using a Doppler catheter in an additional animal. Left ventriculography demonstrated immediate global dilation and depression of systolic function. CONCLUSIONS In the swine model, relatively small doses of intracoronary carbon dioxide cause profound yet reversible global left ventricular dysfunction which appears to be ischemic in origin.

Longer duration of morbid obesity is associated with higher LV mass, poorer LV systolic function, and greater impairment of LV diastolic filling. Weight loss-induced decreases in LV mass and improvements in LV systolic function and diastolic filling are due in part to favorable alterations in LV loading conditions.

BACKGROUND Coronary dissection and thrombosis are important as pathophysiological mechanisms in acute coronary syndromes and as consequences of various interventional procedures. The present study was designed to develop and characterize a simple percutaneous method to produce coronary dissection and thrombosis in the pig. METHODS The porous balloon (Wolinski type) was slightly oversized (balloon-to-artery ratio, 1.21 +/- 0.08) and placed in the left anterior descending artery in 12 domestic pigs using standard percutaneous techniques. The balloon was inflated using a pressure-activated syringe at 5 atm to deliver 1 ml of either saline or a small amount of bovine thrombin (500 units) in saline. The balloon was withdrawn, serial angiograms recorded, and ECG and aortic pressure were monitored throughout. At coronary occlusion or at 30 min, the hearts were removed and fixed for histological analysis. RESULTS Seven pigs received thrombin and five received saline. On microscopic examination the internal elastic lamina was disrupted in all arteries in both groups. Subintimal and medial dissection was noted in 80% of arterial cross sections in the saline group, and 86% in the thrombin group. Partial occlusion of the coronary artery with thrombus was seen in 20% of samples in the saline group and in 43% of the thrombin group. Thrombus with complete occlusion of the coronary artery was observed in 86% of thrombin-treated vessels but in none of the arteries that received saline. Complete occlusion was observed at 28 +/- 9 min by angiography. CONCLUSIONS Percutaneous delivery of a small amount of thrombin through a slightly oversized porous balloon catheter produces coronary dissection and thrombosis in a more reproducible and timely fashion than previously described methods. This model may be useful for testing interventional and pharmacologic treatment strategies.

We have previously demonstrated the utility of time-series analysis applied to 72-hour ambulatory electrocardiographic data in patients with coronary artery disease. The present investigation applied time-series analysis to long-term (120-hour) ambulatory electrocardiographic data to determine the minimal period of monitoring needed (1) to detect periodicity of ischemia-related variables in ambulatory patients, (2) to describe auto-correlation and cross-correlation functions for heart rate and ischemia, and (3) to describe the effects of beta-adrenergic and calcium channel blockade on circadian characteristics and coupling of heart rate and ischemia. A double-blind crossover design was used to obtain 120-hour recordings during placebo, atenolol (200 mg/day), and diltiazem (360 mg/day) administration. During all three treatment periods, distinct circadian variation of heart rate was documented by autocorrelation and Fourier analysis. Ischemia did not exhibit clear periodicity as indexed by autocorrelation in any period; however, it was coupled to heart rate in all treatment periods as reflected in cross-correlation analysis. Although diltiazem did not quantitatively alter the circadian characteristics of heart rate or ischemia, atenolol produced a shift in the coupling between remaining ischemia and heart rate in time. Significant autocorrelation was detected for all treatment periods after 72 hours of monitoring, suggesting that 72 hours is the minimum amount of time needed for analysis of ambulatory electrocardiographic data in patients with coronary artery disease.

Extreme obesity produces increases in circulating blood volume and cardiac output, which are proportional to the excess in adipose accumulation.1-20 In the absence of systemic hypertension, systemic vascular resistance decreases to accommodate the increase in cardiac output.l-‘o Left ventricular enlargement results from the increases in circulating blood volume and cardiac output, and in turn, predisposes the left ventricle to increased wall stress, in accordance with the law of LaPlace.‘-” Eccentric left ventricular hypertrophy is thought to develop in response to, and as a mechanism for, reducing left ventricular wall stress.” Prior postmortem and echocardiographic studies showed that left ventricular hypertrophy frequently occurs in extremely obese subjects, even in the absence of systemic hypertension.4-10 There has been no systematic assessment of factors influencing left ventricular mass in extremely obese subjects or of the effect of weight loss on left ventricular mass in these cases. The present study examines these issues.

BACKGROUND: Local drug delivery is a potential solution to postintervention restenosis. Most catheters developed for local delivery depend upon control of pressure and of delivered volume for optimal performance. The present study was designed to assess the accuracy of current methods for inflation of local delivery catheters compared with a new microprocessor-controlled system specifically designed for this application. METHODS: An in vitro gravimetric testing system was constructed to record developed pressure and delivered volume using a variety of inflation devices and a microporous infusion catheter. Experienced catheterization laboratory personnel were given commercial angioplasty indeflators and a pressure-driven syringe and asked to quickly apply 5 atm and deliver 2.0 ml. A new microprocessor-controlled system was then tested using the same protocol. RESULTS: The time required to reach a plateau pressure was lowest with the pressure-driven syringe (0.164 +/- 0.017 s) and much higher with standard indeflators (2.94 +/- 2.54, 4.64 +/- 2.98, 7.69 +/- 4.89, 8.28 +/- 6.31 s). The corresponding microprocessor-controlled value was much lower than that of the manual systems (0.84 +/- 0.37 s). The variability of plateau pressure, as measured by the standard deviation, was lowest with the pressure-driven syringe (0.029 +/- 0.014 atm) and highest with the manual systems (0.37 +/- 0.26, 0.40 +/- 0.18, 0.44 +/- 0.31, 0.32 +/- 0.10 atm). The microprocessor-controlled system also produced very little variability in pressure (0.08 +/- 0.004 atm). The volume delivered varied significantly with all manual devices (1.77 +/- 0.64, 1.74 +/- 0.66, 1.36 +/- 0.45, 1.80 +/- 0.33 ml) as well as with the pressure-driven syringe (1.86 +/- 0.32 ml), but the volume delivered by the microprocessor-controlled system was highly accurate (1.99 +/- 0.06 ml). CONCLUSIONS: Manual inflation devices do not allow precise control of pressure or volume when used with local delivery catheters. Use of a pressure-driven syringe minimizes pressure error, but does not deliver an accurate volume. The microprocessor-controlled system minimizes pressure and volume error and should maximize transfer efficiency for local delivery catheter systems.

Twenty patients were studied during cardiac catheterization to compare hemodynamic and quantitative angiographic effects of intravenous nicardipine and nitroglycerin. After baseline measurements, nicardipine or nitroglycerin was administered by randomized continuous infusion beginning at 10 micrograms/min titrated to achieve a 10 to 12% reduction in systemic arterial pressure. Hemodynamic measurements and angiography were then repeated. Nicardipine did not change heart rate, and a small decrease (82 +/- 4 vs 75 +/- 4 beats/min) was observed with nitroglycerin, whereas mean arterial pressure decreased similarly (-11%) in both groups. Nicardipine increased (+13%) and nitroglycerin decreased (-21%) cardiac output. Although both drugs were associated with significant reductions in pulmonary artery wedge and pulmonary artery pressures, changes were greater with nitroglycerin for pulmonary artery wedge (-49% vs -26%) and pulmonary artery (-39% vs -13%) pressures, whereas only nitroglycerin reduced right atrial pressure significantly. Neither drug altered left ventricular ejection fraction or pulmonary vascular resistance, and only nicardipine decreased systemic vascular resistance significantly. Quantitative coronary angiography (videodensitometry) showed dilation of the left main, proximal, mid and distal anterior descending and circumflex segments by both nitroglycerin and nicardipine. Nicardipine dilated small (2 mm2) and large (2) arterial segments equally, whereas nitroglycerin showed a proportionately greater effect on small vessels.

This case report describes the evolution of an acute anteroseptal myocardial infarction in a 27-year-old man following intravenous injection of pentazocine and tripelennamine. Subsequent coronary angiography showed normal coronary arteries. Based on the known mechanism of action of these drugs, it is postulated that myocardial infarction resulted from coronary artery spasm secondary to excessive catecholamine stimulation.

Nicardipine a second-generation dihidropyridine calcium antagonist, has been approved in oral formulation for use in the United States, and is under review for parenteral use. Nicardipine is the most vascular-selective agent of this class currently approved and should, on theoretical grounds, be ideal for combination therapy with beta-adrenergic blocking agents. Studies have shown that the combination of nicardipine and beta-blocking agents offers additional efficacy over monotherapy with either agent alone. The hemodynamic profile of combination therapy appears to be especially favorable in patients with diminished left ventricular function needing therapy with agents of both classes. Adverse effects are few and may be improved compared with other agents of the dihidropyridine class.

Ergonovine has become an accepted agent for the provocation of coronary artery spasm. Standard testing protocols generally use either cumulative or single intravenous bolus doses of ergonovine. A disadvantage of such protocols is that spasm may occur in both coronary arteries simultaneously, or during catheter exchange and, if severe, may be difficult to document and manage in some patients with severe myocardial ischemia, especially if using the Judkins technique. Recently, some investigators 1,2 have begun to administer intracoronary ergonovine to allow selective provocation of spasm in a single coronary artery. It has been postulated that this method might offer more precise control of the vasoconstrictor stimulus and a wider margin of safety than is possible with intravenous administration of ergonovine. In addition, this approach may avoid systemic hypertension and occasional systemic adverse effects that may be seen with intravenous ergonovine. Despite increasing use of intracoronary ergonovine administration in patients, it has not been determined whether such administration causes a truly selective vasoconstrictor effect. The present study determines whether intracoronary ergonovine administration causes selective unilateral coronary artery constriction or whether the contralateral coronary artery is affected as well.

Single-plane left coronary angiograms in 18 patients were prospectively analyzed using videoden-sitometry (XR-70 system) and handheld digital calipers to compare arterial dimensions, stenosis dimensions, intraobserver variability and interobserver variability for the methods. A total of 648 arterial segments were measured, yielding a highly significant correlation between videodensitometry and caliper-determined cross-sectional area (r = 0.96, p = 0.0001). Similarly, a highly significant linear relation was observed between videodensitometry and caliper-determined diameter (r = 0.95, p = 0.0001). When data subsets for small, medium and large arterial segments were examined, higher variability in the correlation between videodensitometry and caliper-determined area was observed in the large segments (>10 mm2). In addition, caliper-estimated areas tended to be slightly smaller than videodensitometry-estimated areas in these segments. For diameter estimations, correlations between caliper and videodensitometry data were similar for the entire range of arterial segment sizes. Intra- and interobserver variability was low for both caliper and videodensitometry determination of diameter or area. Thus, over a wide range of arterial dimensions, results obtained with caliper estimates of luminal area and diameter are comparable to those obtained with videodensitometry using the XR-70 system.

Circadian variations of transient myocardial ischemia and heart rate have been identified, but the rhythms and their response to β blockade have not been fully characterized. Time-series analysis, a mathematical technique to describe oscillatory activity occurring within a continuous data set was used, to address these issues. Nine men with coronary artery disease underwent 72 hours of ambulatory electrocardiographic monitoring during therapy with placebo or metoprolol. During administration of placebo, ischemic time and heart rate showed a primary peak with a periodicity of approximately 24 hours with a tight coupling between the 2 variables and a secondary peak with a periodicity of 5 to 8 hours. During metoprolol therapy, heart rate and ischemic variation were reduced and the 24-hour periodicity for heart rate only remained. The 24-hour periodicity for ischemia was eliminated, but the data with 5- to 8-hour periodicity became the major component of the signal.

The value of right-sided cardiac catheterization was assessed prospectively in 200 patients undergoing left-sided catheterization for evaluation of known or suspected coronary artery disease. Before catheterization, data from right-sided catheterization was not felt to be necessary for clinical management. There were 6 +/- 2 extra minutes of procedure time and 86 +/- 63 extra seconds of fluoroscopy time used. Abnormalities were detected in 69 (35%) patients. These findings were unexpected in 37 of these patients and in 3 patients, further evaluation was prompted. However, management was altered in only 3 (1.5%) patients as a result of data obtained by right-sided catheterization. In conclusion this additional procedure rarely adds clinically useful information about patients undergoing left-sided catheterization and angiography for coronary artery disease without a clinical indication for right-sided catheterization.

To define the short-term effects of intravenous nicardipine on exercise-and pacing-induced myocardial ischemia, 15 men with coronary artery disease were studied. Nicardpine was administered as a 2 mg bolus followed by a infusion, titrated to maintain a 10 to 20 mm Hg decrease in systolic arterial pressure. At rest, nicardipine significantly decreased systemic and coronary vascular resistances and left ventricular end-diastolic pressure but increased coronary blood flow, heart rate, and myocardial oxygen consumption. With bicycle exercise performed to evoke myocardial ischemia, nicardipine prolonged exercise duration, time to onset of 1 mm ST segment depression, and increased cardiac work to onset of angina in most patients. These changes in cardiac performance were not associated with alteration in the product of systolic pressure and heart rate or with increased left ventricular end-diastolic pressure. During increased heart rate induced by atrial pacing to cause ischemia, the heart rate threshold for myocardial ischemia was not changed by nicardipine. This occurred despite decreased myocardial oxygen consumption, unchanged coronary blood flow, and otherwise similar hemodynamic changes as those observed during exercise. However, left ventricular end-diastolic pressure remained lower and stroke volume increased more after nicardipine with pacing stress when compared with observations before nicardipine with the same heart rate stress. These findings support beneficial antiischemic actions of nicardipine with possible prevention of ischemia-related left ventricular dysfunction.