Acute pulmonary embolism and cancer: findings from the COPE study.

BACKGROUND: Patients with acute venous thromboembolism associated with cancer have an increased risk of recurrences and bleeding in the long term. RESEARCH QUESTION: To describe the clinical features and short-term course of patients with acute pulmonary embolism (PE) and active cancer, previous cancer or no cancer. STUDY DESIGN AND METHODS: Patients with acute PE included in COPE-prospective, multicentre study of adult patients with acute, symptomatic, objectively diagnosed PE-were classified as having active cancer, previous cancer, or no cancer. RESULTS: Overall, 832 patients had active cancer, 464 with previous cancer and 3660 patients had no cancer at the time of acute PE. The most prevalent primary sites of active cancer were urogenital (23.0%), gastrointestinal (21.0%), and lung (19.8%), with a high prevalence of metastatic disease (57.6%) and ongoing anticancer treatment (16.2%). At discharge, a direct oral anticoagulant was used in 43.1%, 78.8%, and 82.0% of patients with active cancer, previous cancer, and no cancer, respectively. Rates of death in-hospital and at 30 days were higher in patients with active cancer compared to patients with previous cancer and no cancer (7.9% vs. 4.3% vs. 2.2% and 13.8% vs. 5.2% vs. 2.6%, respectively). Rates of major bleeding were 4.8%, 2.6%, and 2.4%, respectively. Among patients with active cancer, lung or metastatic cancer were independent predictors of death; brain, hematological or gastrointestinal cancer had the highest risk of major bleeding. INTERPRETATION: Among patients with acute PE, those with active cancer have high risks for death or major bleeding within 30 days. These risks vary based on primary site of cancer. CLINICAL TRIAL REGISTRATION: clinicaltrial.gov identifier: NCT03631810.

Ultrasound-guided central venous catheter placement through the axillary vein in cardiac critical care patients: safety and feasibility of a novel technique in a prospective observational study.

BACKGROUND: Central venous catheterization is essential for careful administration of fluids and drugs in cardiac critical care patients. The axillary vein might represent an alternative to subclavian and jugular vein accesses, with the advantage of being extra-thoracic, more distal from the pleural space and with more likehood of comfort for the patient. Conventional ultrasound-guided cannulation of the axillary vein is technically demanding and does not guarantee precise visualization of the needle tip. METHODS: We describe a new in-plane technique with a dedicated bracket support for the needle, giving full tip control and continuous visualization of the tip and vessel, making the maneuver easier and safer. In a prospective observational study we also report the feasibility and safety of the novel procedure in a series of 35 cardiac critical care patients, also receiving non-invasive ventilatory support and/or being fully anti-coagulated. RESULTS: With the novel technique, we obtained 97% success with procedural times comparable to other insertion sites and without complications. CONCLUSIONS: Placement of a central line catheter in the axillary vein using a novel ultrasound-guided bracket-assisted technique may be a feasible, safe and rapid alternative to the conventional jugular and subclavian approaches.

History of vasomotor symptoms, extent of coronary artery disease, and clinical outcomes after acute coronary syndrome in postmenopausal women.

OBJECTIVE: Vasomotor symptoms (VMS) during menopausal transition have been linked to a higher burden of cardiovascular risk factors, subclinical vascular disease, and subsequent vascular events. We aim to investigate the association of VMS with the extent of coronary disease and their prognostic role after an acute coronary syndrome. METHODS: The Ladies Acute Coronary Syndrome study enrolled consecutive women with an acute coronary syndrome undergoing coronary angiography. A menopause questionnaire was administered during admission. Angiographic data underwent corelab analysis. Six out of 10 enrolling centers participated in 1-year follow-up. Outcome data included the composite endpoint of all-cause mortality, recurrent myocardial infarction, stroke, and rehospitalization for cardiovascular causes within 1 year. RESULTS: Of the 415 women with available angiographic corelab analysis, 373 (90%) had complete 1-year follow-up. Among them, 202 women had had VMS during menopausal transition. These women had the same mean age at menopause as those without VMS (50 years in both groups), but were younger at presentation (median age 71 vs 76 years; P < 0.001), despite a more favorable cardiovascular risk profile (chronic kidney dysfunction 4.5% vs 15.9%; P = 0.001; prior cerebrovascular disease 4.5 vs 12.2%; P = 0.018). Extent of coronary disease at angiography was similar between groups (mean Gensini score 49 vs 51; P = 0.6; mean SYNTAX score 14 vs 16; P = 0.3). Overall cardiovascular events at 1 year did not differ between groups (19% vs 22%; P = 0.5). CONCLUSIONS: In postmenopausal women with an acute coronary syndrome, a history of VMS was associated with younger age at presentation, despite a lower vascular disease burden and similar angiographically defined coronary disease as compared with women without VMS. No difference could be found in terms of overall clinical outcomes. These results should be interpreted cautiously as all analyses were unadjusted and did not account for risk factor differences between women with and without a history of VMS.

Malignant Cough Syncope from Idiopathic Vagal Inflammation.

We describe the case of a patient with malignant vasodepressive cough syncope. We demonstrated a vaso-vagal mechanism related to left vagal neuritis, by means of laryngoscopy and laryngeal electromyography. The condition resolved with steroid therapy. LEARNING POINTS: Left vagal neuritis should be considered in the differential diagnosis of recent onset repetitive loss of consciousness, in particular if cough related.Steroids were used to successfully treat recent onset cough-related syncope.Relatively simple trials of drug therapy can sometimes avoid intensive investigations; in our case, the use of a systemic steroid would probably have avoided many radiological and endoscopic examinations.

[Treatment of acute coronary syndrome in older adults and high-risk patients."When the going gets tough "]. / Trattamento del paziente con sindrome coronarica acuta in età avanzata e con copatologie. "Quando il gioco si fa duro ".

The increasing life expectancy in older adults and the better survival of patients with multiple pathologies require the capability to treat complex clinical conditions with an increased risk of iatrogenic complications. Nevertheless, recent improvements in the pharmacological and interventional treatment of acute coronary syndrome (ACS) have promoted a shift from therapeutic nihilism to a more active management of complex ACS cases. Despite the paucity of specific randomized clinical trials, observational studies seem to show benefit of an early invasive treatment in these patients. This approach requires close cooperation of clinical intensivists, interventional cardiologists and cardiovascular surgeons either in a specialized heart center or in a network of hospitals.

Predictors of cardiac death in patients with coronary chronic total occlusion not revascularized by PCI.

BACKGROUND: Limited data are available on clinical outcome of patients with previously failed or not attempted chronic total occlusion (CTO) recanalization by percutaneous coronary intervention (PCI). The aim of the study is to determine prevalence and predictors of cardiac death in patients with CTO not revascularized by PCI. METHODS: Double-center study analyzing data of 1.345 consecutive patients with at least one CTO between 1998 and 2008. Of these, 847 patients were successfully revascularized (Revascularized group) and 498 patients were not revascularized (Not revascularized group) either due to failure of CTO-PCI (n=337) or because no attempt was made (n=161). RESULTS: At 4-year clinical follow-up, Not revascularized patients had a significantly higher rate of cardiac mortality (8.5% vs. 2.5%, p<0.0001) and sudden cardiac death (2.7% vs. 0.5%, p=0.001) compared to those Revascularized. The separate adjusted Cox-model analysis made for Not revascularized patients showed the most significant independent predictors of cardiac death were: chronic renal failure [HR (CI), 6.0 (2.66-13.80)], low-LVEF [5.7 (2.84-11.58)], insulin-dependent diabetes mellitus (IDDM) 4.6 [(1.96-10.97)]. In the Revascularized group, the presence of 3-vessel disease was the only significant independent predictor of cardiac death [4.4 (1.40-13.70)]. CONCLUSIONS: CTO patients Not revascularized had a significant higher rate of cardiac mortality and sudden cardiac death compared to those Revascularized. Within Not revascularized patients, the presence of low-LVEF, or CRF or IDDM was associated with an incidence of cardiac death at least 4 times higher than those without the same risk factors.

Improved survival in patients with chronic mild/moderate systolic heart failure followed up in a specialist clinic.

OBJECTIVE: To relate therapeutic issues, comorbidities and functional parameters to mortality/morbidity of mild/moderate heart failure patients. METHODS: From our heart failure clinic, 372 heart failure patients (269 men, aged 66 ± 11 years), with stable heart failure and ejection fraction 45% or less were recruited. Survival curves were estimated according to the Kaplan-Meier method. Associations of protective/risk factors with cardiovascular mortality/morbidity were also evaluated. RESULTS: One hundred and two patients (27%) died (aged 70 ± 10 years at diagnosis, 76 ± 10 at death) during follow-up (overall mortality at 60 months: 19.2%; mean follow-up period: 67 ± 44 months). Cardiovascular deaths were 64 (63% of total deaths, 44 men, age at diagnosis 70 ± 9). Cardiovascular mortality at 60 months was 12%; standardized mortality ratio was 5.9 for women and 6.8 for men. The remaining 38 patients (37% of total deaths, 30 men, age at diagnosis 70 ± 10) died of noncardiovascular causes. Overall, noncardiovascular mortality at 60 months was 7.2%; mean survival time from diagnosis to death was 63 ± 69 months (median 42, Q1 = 27.5, Q3 = 77.7). Average cardiovascular admission rate was 1.63 ± 1.84 admissions/patient. At multivariate analysis, only previous history of myocardial infarction [hazard ratio: 3.62 (1.70-7.73)], class of ejection fraction at diagnosis [hazard ratio: 0.36 (0.32-0.60)], acute cardiac decompensation at any time [hazard ratio: 1.55 (1.32-1.84)], implanted defibrillator [hazard ratio: 0.11 (0.01-0.83)] and use of statins [hazard ratio: 0.08 (0.007-0.42)] were independently associated with cardiovascular mortality. Factors associated to higher annual cardiovascular morbidity were age at diagnosis, chronic renal failure, diabetes, cardiac decompensation at any time, female sex and diuretic therapy. Angiotensin-converting enzyme (ACE) inhibitors and/or angiotensin-receptor-blockers reduced annual cardiovascular morbidity. CONCLUSION: Survival in mild/moderate heart failure patients has consistently improved. Further improvements are warranted in terms of morbidity reduction.

Coronary chronic total occlusions: mid-term comparison of clinical outcome following the use of the guided-STAR technique and conventional anterograde approaches.

AIM: There are limited data on the mid-term safety following the use of the guided-subintimal tracking and re-entry (guided-STAR) technique for the treatment of chronic total occlusions (CTO) and concerns have arisen about a potential increased risk of stent thrombosis (ST). OBJECTIVES: The aim of this study was to evaluate the mid-term safety in terms of cardiac death and ST after recanalization using the contrast guided-STAR technique when compared to conventional anterograde CTO recanalization (CA-CTO). METHODS AND RESULTS: This retrospective study analyzed 355 consecutive patients with successful angiographic recanalization (residual stenosis <20% and TIMI flow grade ≥2) of CTO lesion. Seventy-four (20.8%) underwent guided-STAR and 281 (79.2%) had CA-CTO. Survival rates were estimated using the Kaplan-Meier method. Compared to CA-CTO patients, the rate of the following clinical, angiographic, and procedural characteristics were significantly higher in guided-STAR patients: hypercholesterolemia (84 vs. 67%, P = 0.004), previous CABG (41.3 vs. 15.7%, P < 0.0001), three-vessel disease, (62.7 vs. 47%, P = 0.019), right coronary artery CTO (62.7 vs. 41.6%, P = 0.002), stent length (68.15 vs. 54.05 mm, P < 0.0001). A drug-eluting stent was implanted in the majority of cases (89.2% guided-STAR vs. 93.5% CA-CTO). At a median follow-up of 779 days (IQR 495-1035), there were no significant differences in cardiac survival (97.2 vs. 97.5%, Log-rank P = 0.912) and cumulative ARC ST rates (2.8 vs. 1.8%, Log-rank P = 0.610) for guided-STAR and CA-CTO patients, respectively. The rate of restenosis was significantly higher in the guided-STAR group compared to the CA-CTO group (54 vs. 30%, Log-rank P < 0.0001). The adjusted Cox proportional-hazard analysis for procedural technique showed that the only significant independent predictor of restenosis was the stent length (HR, 1.017; 95% CI, 1.008-1.027; P < 0.0001). CONCLUSION: At mid-term follow-up, the guided-STAR was not inferior to CA-CTO in terms of safety. The only significant independent predictor of restenosis was the stent length.

Effect of partial inhibition of fatty acid oxidation by trimetazidine on whole body energy metabolism in patients with chronic heart failure.

OBJECTIVE: Trimetazidine may have beneficial effects on left ventricular (LV) function in patients with systolic heart failure. The authors assessed whether long-term addition of trimetazidine to conventional treatment could improve, along with LV function, resting whole body energy metabolism in patients with chronic systolic heart failure. DESIGN: Single blind randomised study. SETTING: University Hospital. PATIENTS: 44 patients with systolic heart failure receiving full medical treatment. INTERVENTIONS: Indirect calorimetry and two-dimensional echocardiography at baseline and after 3 months. MAIN OUTCOME MEASURES: Whole body resting energy expenditure (REE), percentage of predicted REE, LV ejection fraction (EF), NYHA class, quality of life. RESULTS: Trimetazidine increased EF compared with conventional therapy alone (from 35±8% to 42±11% vs from 35±7% to 36±6%; p=0.02, analysis of variance for repeated measures). NYHA class and quality of life also improved compared with conventional therapy (p<0.0001). REE (from 1677±264 to 1580±263 kcal/day) and percentage of predicted REE (based on the Harris-Benedict equation: from 114±10% to 108±9%) decreased in the trimetazidine group, but not in the control group (REE from 1679±304 to 1690±337 kcal/day and percentage of predicted REE from 113±12% to 115±14%). The variation was different between groups (p=0.03 and 0.023, respectively). CONCLUSIONS: In patients with systolic heart failure, improvement in functional class and LV function induced by middle-term trimetazidine therapy is paralleled by a reduction in whole body REE. The beneficial cardiac effects of trimetazidine may be also mediated by a peripheral metabolic effect.

Long-term follow-up of multivessel percutaneous coronary intervention with drug-eluting stents for de novo lesions with correlation to the SYNTAX score.

BACKGROUND: Stent thrombosis (ST) and restenosis are concerns after percutaneous coronary intervention (PCI). Limited information exists concerning clinical and angiographic outcomes following multiple stent insertion. We therefore present the long-term outcome from drug-eluting stent (DES) insertion and correlate this with the Syntax score. METHODS AND RESULTS: Between April 2002 and 2006, all patients that underwent multilesion PCI (defined as ≥4 DES) were included for analysis, and follow-up commenced from the point where the fourth stent was inserted. Three hundred and seventy-four patients were identified, comprising 1972 lesions; 99% had clinical (30±16 months), and 72% had angiographic follow-up. The mean number of stents implanted was 5.7±1.9 and with length of 137±50 mm and Syntax Score of 24±8. The Syntax score (SS) did not predict major adverse cardiac events (MACE) at long-term follow-up, which occurred in 33% in the low SS (<22), 34% intermediate SS (22-32) and 40% in the high SS (>33); P=ns. However, the number of stents implanted correlated with events [MACE: 12% (4 DES), 35% (4-6 DES), 61% (>6 DES)]. There were 11 (2.9%) definite and probable ST: four acute and subacute, three late, and four very late. CONCLUSIONS: This study demonstrates an acceptable occurrence of myocardial infarction, death, repeat revascularisation, and ST in patients with multivessel de novo lesions, which had better correlation with the number of DES inserted than the Syntax score.

Clinical outcomes after unrestricted implantation of everolimus-eluting stents.

OBJECTIVES: The aim of this study was to evaluate the efficacy and safety of unrestricted everolimus-eluting stent (EES) implantation in a contemporary cohort of real-world patients. BACKGROUND: The randomized SPIRIT (A Clinical Evaluation of the XIENCE V Everolimus Eluting Coronary Stent System in the Treatment of Patients With de Novo Native Coronary Artery Lesions) trials have evaluated the performance of EES, resulting in their approval by the Food and Drug Administration, but data regarding unselected usage, including off-label indications are lacking. METHODS: Consecutive patients treated with EES (either PROMUS, Boston Scientific Corp., Natick, Massachusetts, or XIENCE-V, Abbott Vascular Devices, Santa Clara, California) between October 2006 and February 2008 were analyzed. End points were cardiac death, myocardial infarction (MI), ischemic-driven target lesion revascularization (TLR), stent thrombosis (ST), and major adverse cardiac events (MACE) (a composite of cardiac death, MI, TLR) during follow-up. RESULTS: We identified 345 patients (573 lesions) treated with EES. The majority of patients (71.9%) were treated for > or =1 off-label or untested indication. Clinical follow-up was completed in 99%. At a median follow-up of 378 days (interquartile range 334 to 473), MACE occurred in 36 (10.6%) patients, TLR in 27 (7.9%), MI in 7 (2.1%), and cardiac death in 7 (2.1%). Definite and probable ST was observed in 3 (0.9%) cases. Off-label EES implantation was not associated with a statistically significant increased risk of MACE (12.2% vs. 6.3%, p = 0.17), TLR (9.3% vs. 4.2%, p = 0.18), or ST (0.8% vs. 1.1%, p = 1.0). On multivariable analysis, previous bypass surgery (p = 0.002) and diabetes (p = 0.03) were associated with MACE. CONCLUSIONS: In unrestricted daily practice, EES were implanted predominantly for off-label indications and associated with a relative low rate of MACE and TLR.

Metabolic therapy of heart failure.

Alterations of cardiac metabolism can be present in several cardiac syndromes. Heart failure may itself promote metabolic changes such as insulin resistance, in part through neurohumoral activation, and determining an increased utilization of non-carbohydrate substrates for energy production. In fact, fasting blood ketone bodies as well as fat oxidation have been shown to be increased in patients with heart failure. The result is depletion of myocardial ATP, phosphocreatine and creatine kinase with decreased efficiency of mechanical work. A direct approach to manipulate cardiac energy metabolism consists in modifying substrate utilization by the failing heart. To date, the most effective metabolic treatments include several pharmacological agents, such as trimetazidine and perhexiline, that directly inhibit fatty acid oxidation. These agents have been originally adopted to increase the ischemic threshold in patients with effort angina. However, the results of current research is supporting the concept that shifting the energy substrate preference away from fatty acid metabolism and toward glucose metabolism could be an effective adjunctive treatment in patients with heart failure, in terms of left ventricular function and glucose metabolism improvement. In fact, these agents have also been shown to improve overall glucose metabolism in diabetic patients with left ventricular dysfunction. In this paper, the recent literature on the beneficial therapeutic effects of modulation of cardiac metabolic substrates utilization in patients with heart failure is reviewed and discussed.

Differential long-term effects of carvedilol on proinflammatory and antiinflammatory cytokines, asymmetric dimethylarginine, and left ventricular function in patients with heart failure.

Neuroendocrine/inflammatory and endothelial functions have been indicated as crucial for heart failure (HF) patients. We evaluated relation in HF patients among cytokines and asymmetric dimethylarginine (ADMA) and left ventricular ejection fraction (LVEF) at baseline and after long-term administration of carvedilol. Interleukin 10 (IL-10), interleukin 18 (IL-18), and ADMA were measured in 22 NYHA class II to IV HF patients at baseline and after 40 +/- 14 months of carvedilol treatment. Patients were divided into 2 groups according to whether, after treatment with carvedilol, LVEF had increased at least 5% (responders) or less than 5% (non-responders). In responders (11 of 22 patients), LVEF increased from 38 +/- 6% to 50 +/- 7%, (P < 0.001); in non-responders, it decreased from 36 +/- 9% to 31 +/- 6%, (P = 0.02); NYHA class significantly decreased in both groups. IL-18 decreased in responders (from 586.4 +/- 128 to 183.13 +/- 64.4 pg/mL; P < 0.001) and in non-responders (from 529.3 +/- 116.25 to 142.4 +/- 58.9 pg/mL; P < 0.001). IL-10 increased in responders (from 0.49 +/- 0.25 to 2.01 +/- 1.01 pg/mL; P < 0.001) and in non-responders (from 0.64 +/- 0.31 to 1.33 +/- 0.59 pg/mL; P < 0.001). Conversely, ADMA levels decreased only in responders (from 0.67 +/- 0.16 to 0.44 +/- 0.15 micromol/L; P < 0.001), and an inverse correlation was observed between basal ADMA levels and changes in LVEF after treatment. In HF patients, carvedilol appears to reduce symptoms and the expression of inflammation, regardless of the LV functional response. In those patients showing improvement of LVEF, the reduction of inflammation is paralleled by a reduction of ADMA. We surmise that carvedilol could be effective at various independent levels as a result of possible pleiotropic effects of this agent.

New directions in the treatment of heart failure: targeting free fatty acid oxidation.

The possibility of modifying cardiac metabolism by switching the fuel used by the myocardium could become increasingly important. Inhibitors of free fatty acid (FFA) oxidation could have an important role in therapeutic strategy for patients with heart failure, and shifting the energy substrate preference away from FFA metabolism and toward glucose metabolism may be an effective adjunctive treatment. Additionally, abnormalities of glucose homeostasis in patients with heart failure contribute to the progression of the primary disease. If not adequately treated, these abnormalities can contribute to the occurrence of complications, including severe left ventricular dysfunction. Apart from meticulous metabolic control of frank diabetes, special attention should be paid to insulin resistance, a distinct clinical entity. The observed combined beneficial effects of FFA inhibitors on left ventricular function and glucose metabolism represent an additional advantage of these drugs, especially when abnormalities of myocardial and glucose metabolism coexist.

The anti-ischemic effect of trimetazidine in patients with postprandial myocardial ischemia is unrelated to meal composition.

BACKGROUND: Previous studies provide evidence for a significant reduction of coronary flow reserve after ingestion of meals of different compositions. A possible role of hyperinsulinemia and increased free fatty acid levels, which are deleterious during acute myocardial ischemia and reperfusion, has been hypothesized. We assessed in patients with stable coronary disease the effects of high-fat meals (HFMs) and high-carbohydrate meals (HCMs) on ischemic threshold and stress left ventricular function on placebo and after partial fatty acid inhibition by trimetazidine (TMZ). METHODS: Ten patients (9 men, age 68 +/- 7 years) were allocated to placebo and TMZ (40 mg TID), both administered in the 24 hours preceding testing, according to a randomized double-blind study design. All patients underwent stress (treadmill exercise testing according to the Bruce protocol) echocardiography after fasting (8 hours) and after an HFM and HCM (2 hours) either on placebo or on TMZ. Time to 1-mm ST-segment depression (time to 1 mm) and stress wall motion score index (WMSI) were evaluated. RESULTS: An HFM did not affect exercise variables compared with fasting, whereas an HCM resulted in a reduction of the ischemic threshold (time to 1 mm from 402 +/- 141 to 292 +/- 123 seconds, P = .025). Compared with placebo, TMZ improved time to 1 mm after fasting, HFM, and HCM (432 +/- 153 vs 402 +/- 141, 439 +/- 118 vs 380 +/- 107, 377 +/- 123 vs 292 +/- 123, F(1,9) = 26.91, P = .0006). Compared with placebo, on TMZ, stress WMSI decreased from 1.55 +/- 0.25 to 1.29 +/- 0.14 after fasting, from 1.57 +/- 0.10 to 1.39 +/- 0.28 after HFM, and from 1.64 +/- 0.21 to 1.39 +/- 0.21 after HCM (F(1,9) = 37.04, P = .0002). Interestingly, stress WMSI on TMZ was never different from rest WMSI on placebo. CONCLUSIONS: In patients with coronary disease, exercise testing after an HCM results in more severe myocardial ischemia compared with that after an HFM. The observed beneficial effects of the partial fatty acid inhibitor TMZ seem to be unrelated to meal composition and are possibly caused by the better glucose use induced by the drug.

Nitric-oxide mediated effects of transdermal capsaicin patches on the ischemic threshold in patients with stable coronary disease.

BACKGROUND: Capsaicin has been shown to exert direct vasodilating effects through increased calcitonin gene-related peptide (CGRP) release. However, no data exist on its effect following systemic administration in humans. METHODS: Twelve male patients with stable coronary disease and a persistently positive exercise were selected for study. According to a double blind, placebo-controlled, cross-over study, patients were randomized to placebo or 3 g oleic capsaicin-containing patches, on 2 different days and with a 2-day interval between treatments. Patients performed treadmill exercise testing according to the Bruce protocol. Time to 1 mm ST segment depression and to peak exercise, maximal ST segment depression, and the number of ECG leads showing diagnostic changes were also measured. Blood samples for nitric oxide (NO) and CGRP were drawn at baseline, 2, 6, and 24 hours after exercise. RESULTS: On placebo, all patients had a positive ECG during exercise test. Only 1 patient experienced angina, on both treatments. With capsaicin, 1 patient had a negative exercise, while 8 patients significantly increased time to 1 mm ST depression from 328 +/- 167 to 401 +/- 174 seconds (P = 0.01). Of the remaining patients, 1 did not show any changes and 2 showed a worse ischemic threshold when on capsaicin. CGRP levels were not significantly different between placebo and capsaicin treatment. Conversely, when on capsaicin, NO significantly increased at 6 hours. CONCLUSIONS: Transdermal capsaicin may improve ischemic threshold in patients with stable coronary disease, probably through arteriolar vasodilation. Increased capsaicin-induced NO availability could represent the principal mechanism of action.