CCS Class Research Articles

Heart rate modulation in stable ischemic heart disease: what we have learned from the SIGNIFY study?

Elevated heart rate is a marker of cardiovascular risk in patients with stable coronary artery disease. The addition of ivabradine to standard therapy to reduce heart rate did not improve outcomes in the recent SIGNIFY trial. Moreover, a significant interaction between the effect of ivabradine among subgroups with and without angina with a worse outcome in patients in CCS class >II at baseline was detected. The explanation for this surprising finding despite a significant reduction in angina and myocardial revascularization procedures is uncertain. A J-curve for heart rate was not demonstrated. We speculate a significant interference on adverse events (mainly atrial fibrillation and consequently acute coronary syndromes) and on the outcome of unfavorable interactions between ivabradine and diltiazem, verapamil and strong inhibitors of CYP3A4 (4.6% of the total population). Excluding this subgroup, there are no significant changes in outcomes between the two treatment groups (ivabradine and placebo). In conclusion, heart rate is a marker of risk but is not a risk factor and/or a target of therapy in patients with stable coronary artery disease and preserved ventricular systolic function. Standard doses of ivabradine are indicated for treatment of angina as an alternative or in addition to beta-blockers, but should not be administered in association with CYP3A4 inhibitors or heart rate-lowering calcium antagonists.

Current status and influence factors of beta blocker prescription in Chinese patients with stable angina pectoris

To analyze the status of beta blockers (BBs) prescription in Chinese patients with stable angina pectoris. To determine the gap between clinical practice and treatment guidelines and factors influencing the use of BBs in Chinese patients. A questionnaire survey was conducted in patients diagnosed with chronic stable angina pectoris in 2011. A total of 298 Chinese hospitals attended the survey. The questionnaire collected patient demographic information, clinical and medication information. In the analysis, patients were divided into two groups according to whether they were on BBs at the time of the interview. Hospital characteristics, patient demographic information, cardiovascular risk factors, diagnostic method of coronary heart disease, past history of coronary revascularization and use of secondary prevention medications were compared between the two groups. Binary logistic regression analysis was used to identify factors related to BBs use. Patients were followed-up for 3 months. Patients who were on BBs at baseline were divided into two groups according to whether they were still on BBs after 3 months. Comparison of the clinical information previously mentioned was made between the two groups, and binary logistic regression analysis was used to identify factors related to BBs adherence. Of the 5 011 questionnaires, 2 859 cases were male, mean age was (67.6 ± 11.5) years old, 3 060 (61.1%) patients were on BBs at baseline. Binary logistic regression analysis showed that when adjusted for other factors, old age (OR = 0.895, 95% CI 0.849-0.944, P<0.001) was related to no BBs use, while comorbidity with hypertension (OR = 1.255, 95% CI 1.103-1.427, P = 0.001) or hyperlipidemia (OR = 1.456, 95% CI 1.287-1.648, P<0.001), diagnosed with coronary disease by imaging (OR = 1.250, 95% CI 1.070-1.461, P = 0.005) and past history of coronary revascularization (OR = 1.490, 95% CI 1.220-1.820, P<0.001) were related to higher percentage of BBs use. A total of 2 533 cases (82.8%) were still taking BBs 3 months after baseline interview. Binary logistic regression analysis showed that, when adjusted for other factors, treated at traditional Chinese medical hospitals (OR = 1.612, 95% CI 1.154-2.251, P = 0.005), low levels of education (OR = 1.316, 95% CI 1.151-1.504, P<0.001), hypertension (OR = 1.345, 95% CI 1.096-1.651, P = 0.005), high baseline heart rate (OR = 1.020, 95% CI 1.010-1.030, P<0.001) and diagnosed with coronary disease by imaging (OR = 1.342, 95% CI 1.095-1.644, P = 0.005) were factors related to higher BBs adherence, while low baseline CCS class (OR = 0.794, 95% CI 0.704-0.896, P<0.001) was related to lower BBs adherence. In Chinese patients with clinically diagnosed chronic stable angina, BBs use was not sufficient. Old age, comorbidity with hypertension or hyperlipidemia, past history of coronary revascularization were independently related to higher percentage of BBs use. Treated at traditional Chinese medical hospitals, low levels of education, hypertension, high baseline heart rate and diagnosed with coronary disease by imaging were independent factors related to higher BBs adherence, while low baseline CCS class was related to lower adherence.

Eight-year cohort study of octogenarians undergoing aortic valve replacement with or without concurrent coronary artery bypass grafting

Background: Given the introduction of transcatheter aortic valve implantation (TAVI), there is significant interest in evaluating outcomes of aortic valve replacement (AVR) with or without(+/-) concurrent coronary artery bypass grafting (CABG) especially in high-risk patients. We reviewed the characteristics and outcomes of octogenarians undergoing isolated AVR and AVR+CABG. Methods: All patients 80 years of age or older undergoing AVR+/-CABG at Auckland City Hospital during 2005-2012 were included, and their characteristics and outcomes analysed. Results: There were 93 and 104 octogenarians respectively undergoing isolated AVR and AVR+CABG with mean follow-up of 4.4+/-2.2 years and 4.1+/-2.3 years. On average 10 more cases of AVR+/-CABG per year were performed since 2010 when TAVI was started at our centre. AVR+CABG patients have significantly higher proportion with history of myocardial infarction, left main and three vessel disease (all P<0.005), higher average CCS and NYHA class (both P<0.001), impaired renal function (P=0.019), higher STS score (6.9% vs 4.9%, <0.001) and longer cardiopulmonary bypass and cross-clamp time (both P<0.001) compared to AVR. They also had significantly higher rate of operative mortality (6.7% vs 0.0%, P=0.015) and prolonged ventilation>24 hours (23.1% vs 10.7%, P<0.001), but similar late mortality (P=0.195). Survival at 1, 3 and 5 years were 94.6%, 82.6% and 73.0% for AVR and 91.3%, 86.1% and 67.6% for AVR+CABG. Conclusion: AVR+CABG had significantly higher but acceptable operative mortality in octogenarians than AVR. These factors are important for the consideration of patients undergoing AVR+/-CABG or TAVI+/-percutaneous coronary intervention, where age alone should not exclude someone from surgery.

0148: Intramyocardial transplantation of mesenchymal stromal cells for chronic myocardial ischemia and decreased left ventricular function: 1-year results of the MESAMI phase I clinical trial

Our aim was to investigate the safety and feasibility of transendocardial injections guided by 3-dimensional NogaStar XP mapping of autologous bone marrow-derived mesenchymal stromal cells (MSC) in patients with chronic myocardial ischemia and left ventricular dysfunction. The MESAMI 1 trial is a bicentric phase 1 study, including 10 patients with chronic myocardial ischemia. The inclusion criteria were: NYHA Class II-IV and/or angina pectoris CCS Class III or IV, chronic ischemic cardiomyopathy with LVEF ≤35%, optimal medical and revascularization therapies, and reversible perfusion defect by SPECT. Bone marrow was obtained by aspiration from the iliac crest and MSC were expanded in culture for 17 days. Transendocardial injections (n=14-16) of autologous bone marrow MSC were made into viable muscle in border zones of left ventricular scar. Bone marrow volume was 16.8±2.0ml, and patients received 61.5* 10 6 MSC. After 1-month follow-up (FU), the primary end-point of safety and feasibility was met since all patients tolerated the procedure with no adverse events due to the procedure and the cell therapy product. Secondary endpoints between baseline and 3-month FU showed a significant decreased of summed stress score measured by SPECT from 34.1±8 to 25.3±9.5(p<0.05). This effect was not maintained at 12 months (32.1±8.0, NS). The echocardiographic LVEF improved significantly of more than 6% from 29.4±6.5% to 35.9±6.7% (p<0.001) at 3 months and was maintained up to 12-month FU (35.7±8.1%; p<0.001). Others parameters including NYHA, 6-minute walk test, VO 2 peak, and Quality of life (Qol) showed a trend toward improvement at 3 months compared to baseline and up to 12 months except for Qol. We demonstrated the safety and the feasibility of this innovative treatment. A randomized, double blind, multicenter, placebo-controlled clinical trial (MESAMI 2) will evaluate the efficiency of this procedure in a larger population.Clinical Trial Registration: NCT01076920

Antegrade insertion in retrograde device: the AIRD technique. An efficient strategy in retrograde revascularization of chronic total occlusions

Received 4 July 2014; revision accepted for publication 14 October 2014. A 67-year-old diabetic man was admitted for stable angina (CCS class II) despite optimal medical therapy. The echocardiogram showed hypokinesia of the lateral wall, with mild reduction of the left ventricular ejection fraction (50%). Coronary angiography revealed a CTO of the LCx, receiving collaterals (CC2) from the LAD via septal branches. LCx CTO revascularization was indicated. After a first unsuccessful antegrade attempt, we opted for a retrograde approach. A right 7-Fr femoral access was performed and a 7-Fr XB 4 guiding catheter (Cordis Co., USA) introduced in the left main coronary artery. A retrograde Sion guidewire (Asahi Intec Co., Japan) was employed with a Corsair microcatheter (Asahi Intec Co., Japan), and successfully reached the distal cap of the LCx CTO. A Miracle 6 guidewire (Asahi Intec Co., Japan) was able to cross the lesion retrogradely, and was inserted into the guiding catheter. However, the microcatheter was not able to advance because of the severe angulation of the LCx and Antegrade insertion in retrograde device: the AIRD technique. An efficient strategy in retrograde revascularization of chronic total occlusions

Abstract 11123: Outcomes After Percutaneous Coronary Intervention for Patients With Stable Coronary Disease and Left Ventricular Systolic Dysfunction

Background: Clinical trial data suggest a modest improvement in outcomes when coronary bypass surgery (CABG) is added to medical therapy for patients with stable coronary artery disease (CAD) and left ventricular systolic dysfunction (LVSD). However, limited data are available to understand the impact of percutaneous coronary interventions (PCI) on mortality for patients with stable CAD and LVSD. Methods: We studied 901 patients in the Duke Databank for Cardiovascular Diseases. All patients underwent a coronary angiogram at Duke University for suspected CAD between 1995 and 2012. Patients included in the analysis all had CAD amenable to PCI (&gt;50% stenosis) in at least 1 vessel, reduced LVEF (&lt; 35%), and stable CAD. Patients with CCS class III or IV angina or CABG within 30 days were excluded. Of 901 patients, 259 were treated with PCI and 642 were treated with medical therapy. Propensity scores for PCI, created from 24 different variables (including age, LVEF, comorbid conditions, and medications), were used to assemble a matched cohort of 444 patients (222 pairs) receiving PCI or medical therapy alone. A survival curve was derived using the Kaplan-Meier method and the hazard ratio (HR) for mortality was estimated using Cox regression modeling. Results: In the matched cohort, the mean age was 63 years with 321 (72%) males. Three-vessel disease was present in 70 patients (16%). The mean EF was 27% and 153 (35%) reported NYHA Class III/IV symptoms; 392 (88%) were treated with beta-blockers and 378 (85%) with ACE-inhibitors or ARBs. Over 12 years of follow-up, patients in both groups had similar mortality (Figure), HR 0.87 (95% confidence interval 0.68-1.10). Conclusion: In this well-profiled, propensity-matched cohort, there was no significant difference in long-term mortality between patients treated with medical therapy alone or with medical therapy plus PCI. More studies are needed to understand the impact of PCI on other outcomes including symptoms and functional status.

The beneficial effect of extracorporeal shockwave myocardial revascularization in patients with refractory angina.

The incidence of patients with refractory angina (RA) is increasing. Medical therapy for RA is limited and prognosis is poor. Experimental data suggest that the use of Extracorporeal shockwave myocardial revascularization (ESMR) may contribute to angiogenesis and improve symptoms of angina in patients with RA. Purpose of our study is to determine the efficacy of cardiac shock wave therapy (ESMR) in the management of patients with nonrevascolarized coronary artery disease (CAD). We performed a prospective cohort study to examine the efficacy of ESMR applcation in patients with RA despite optimal medical therapy, not suitable for further PCI or CABG. Characteristics such as angina class scores (CCS class score), nitroglycerin consumption and hospitalization rate among cases (patients with RA who received ESMR) and controls (patients with RA who did not receive ESMR) were compared at baseline and 6 months after ESMR therapy. In patients receiveing d ESMR the effect of on cardiac perfusion was assessed. There were 43 patients in the case group and 29 patients in the control group. The mean age of the patients was 70 ± 9.5 years in the case group and 71 ± 5.3 years in the control group. Other characteristics (diabetes, coronary artery bypass graft, percutaneus coronary intervention, baseline CCS class score) were similar in both groups. There was a significant improvement in CCS class score (1.33 ± 0.57 in cases and 1.92 ± 0.69 in controls; p = 0.0002), nitroglycerin consumption (20% in case cases, and 44.8% in controls; P < 0.03) and hospitalization rate significantly reduced (13.9% in case cases, and 37.9% in controls; P < 0.03). The patients who received ESMR, there was a significantly improvement in myocardial perfusion after 6 months with a 33% relative reduction of summed stress score (SSS) (p = 0.002). This case control study demonstrates the beneficial effect of ESMR therapy on cardiac symptoms, myocardial perfusion and reduced hospitalization in patients with refractory angina. Ther current study supports a role for ESMR as a non-invasive therapuetic option for patients with RA.

LEFT MAIN INTERVENTIOIN IN A STANDALONE PCI CENTRE - A RECENT 5 YEAR EXPERIENCE

LEFT MAIN INTERVENTIOIN IN A STANDALONE PCI CENTRE - A RECENT 5 YEAR EXPERIENCE

IMMEDIATE CLINICAL OUTCOME OF ROBOTIC ASSISTED CABG IN PATIENTS WITH PREVIOUS HEART SURGERY

Redo Coronary artery bypass graft surgery on cardiopulmonary bypass is associated with significant morbidity and mortality in patients with previous heart surgery. In high risk patients like this, minimally invasive robotic-assisted surgical techniques can reduce adverse events, having a faster recovery and return to their normal activities. We evaluate the postoperative evolution of three patients with previous heart surgery that were treated with robotic-assisted coronary artery bypass grafting. We perform single coronary artery bypass graft surgery off pump in three male patients, between 2008 and 2013, using the DaVinci Si System. The three of them had previous aortocoronary bypass surgery without the utilization of Leith internal thoracic artery (LITA). Average age was 72.99 + 5.99 years old. The three procedures were urgent, and the patients were one in CCS Class 4a, other in CCS Class 4b and other in CCS Class 4c. All of them were diabetics, with no renal dysfunction. Surgery was performed using off pump technique, harvesting the LITA with the robot, and performing the anastomosis of IMA to LAD through a small left anterior minithoracotomy. No patient died or had any postoperative complication. The average ICU stay was of 1.3 + 0.58 days with a maximum ICU days of 2. The average hospital stay was of 3.3 + 0.58 days with a maximum hospital days of 4. The immediate postoperative results of robotic assisted single coronary artery bypass surgery in patients with previous heart surgery demonstrate great reproducible and efficacious results. This alternative approach enables possibility of reduce morbidity and mortality, with a faster recovery and return to their daily activities. Though our experience needs to evaluate more patients with this condition, the future results seem promising.

THIRTY-YEARS OF STANDALONE PCI: EXPERIENCE FROM A HIGH VOLUME CANADIAN CENTRE

The safety of PCI without on-site cardiac surgery has been an ongoing debate since the early 1980’s. However, success rate has improved and acute reocclusion rate reduced since the introduction of stents and new antiplatelet therapy in the 1990s. PCI is now the predominant revascularization modality for coronary disease(CAD) worldwide and where available, primary PCI has become the standard of care for STEMI. In Ontario, 5 new standalone PCI centres have been established in the past 14 years. However, elective standalone PCI remained a Class IIb indication in the 2011 ACCF/AHA/SCAI guidelines. Nonetheless, the recent C-PORT and MASS COM trials in the US concluded that in non-emergency patients, standalone PCI is non-inferior to that performed in centres with on-site cardiac surgery. The Royal Alexandra Hospital performed the first standalone PCI in Canada in 1981 and has provided PCI services to a full spectrum of CAD patients ranging from elective, in-hospital to emergency cases with STEMI and cardiogenic shock. Surgical backup is located at the University of Alberta Hospital 6 km away. Joint case conference is conducted weekly with the cardiac surgery program. In the first 30 years, 23,261 PCIs were performed. We report our 30-year standalone experience, which we believe is the largest single centre experience in literature to date. PCI volumes, clinical and procedural characteristics, lesion success, emergency coronary bypass and mortality rates were collected and reported for the 30-year period. Results for 2006-2011, a period most relevant to current practice were compared with the most recent US PCI data. PCI volumes, CCS Class 4 patients, ad hoc, rescue and primary PCIs all increased significantly over the 30-year period. Success and emergency coronary bypass rates also improved (see Table). For 2006-11, our success, emergency CABG and 30-day mortality rates (96.5, 0.04, 1.1%) compared favorably with National Cardiovascular Data Registry (93-94, 0.3-0.4, 1.2-1.7 %*), C-PORT (93.4-94.1, 0.2, 0.8-0.9 %**) & MASS COM(95.6-97.1, 0.1-0.3, 0.3-0.7 %). PCIs can be performed safely in an experienced, high volume standalone centre with excellent success and very low complication rates. These results support the safety of establishing new standalone PCI centres to meet the growing population demand for percutaneous revascularization for coronary disease.

EFFECT OF NICORANDIL IN PATIENTS WITH REFRACTORY ANGINA AND ADVANCED CORONARY ARTERY DISEASE

Refractory angina (RFA) is a chronic morbid condition hampering the quality of life of thousands of Canadians and effective therapies are desperately needed. Nicorandil is a nicotinamide vasodilator with cardioprotective effects that has been shown to improve cardiac outcomes in patients with stable coronary artery disease (CAD). Nicorandil has never been studied in patients with refractory angina. We investigated the safety and efficacy of nicorandil in patients with advanced coronary artery disease unsuitable for revascularization and persistent angina (CCS Class II to IV) despite maximal tolerable doses of two anti-angina agents, and compared it with similar control patients not exposed to nicorandil. Consecutive patients were selected from our RFA clinic from August 2009 to August 2013 and followed-up for at least 6 months. Nicorandil was available via the Health Canada’s special access program, and a pharmacist dedicated to the program monitored observance to nicorandil and the occurrence of drug-related adverse effects. We assessed the association between nicorandil and cardiovascular outcomes (1st endpoint) and CCS angina class (2nd endpoint) in patients with RFA. Forty patients treated with maximum orally tolerated dose of Nicorandil (up to 30 mg three times daily) were compared to 38 control patients (total n = 78). Baseline characteristics and cardiovascular status were similar in both groups as shown in Table 1. Over a median follow-up of 15 months, fewer patients treated with nicorandil experienced the combined occurrence of death or heart transplant + acute coronary syndrome + coronary revascularization + hospitalization rates at 1-year for angina compared to control patients (37.5% vs. 71.1%, p < 0.05). Nicorandil was associated with a significant improvement in the functional status, as shown in the figure.View Large Image Figure ViewerDownload (PPT) In patients with advanced coronary artery disease and RFA, Nicorandil is associated with both a reduction on cardiovascular events and improvement in functional class.

COMPARISON OF RISK-ADJUSTED MODELS FOR EARLY AND LATE MORTALITY FOLLOWING CABG SURGERY

COMPARISON OF RISK-ADJUSTED MODELS FOR EARLY AND LATE MORTALITY FOLLOWING CABG SURGERY

Predictors of response to intramyocardial bone marrow cell treatment in patients with refractory angina and chronic myocardial ischemia

BackgroundWe previously showed that intramyocardial bone marrow cell (BMC) injection in patients with refractory angina and chronic myocardial ischemia improves myocardial perfusion, cardiac function and disease-related complaints. Treatment effect varied between patients, but the predictors of response remain to be identified. Therefore, the aim of the present study was to assess whether patient characteristics, procedural data and baseline measurements influence the response to intramyocardial BMC treatment in a large cohort of refractory angina patients. Methods and resultsIn 120 patients (64±9years, 88% men) with refractory angina, 97±13×106 BMCs were injected intramyocardially in regions with stress-inducible ischemia as assessed by single photon emission computed tomography (SPECT). Canadian Cardiovascular Society angina (CCS) class, quality-of-life score, exercise testing, SPECT and magnetic resonance imaging were performed at baseline and at 3months follow-up demonstrating significant improvements in CCS class, quality-of-life, exercise capacity, myocardial perfusion and left ventricular function (all variables P<0.001). Multivariate analysis was performed to evaluate the influence of patient characteristics, procedural data and baseline measurements on BMC treatment response. Based on the improvement of myocardial perfusion at stress, diabetes and a large number of ischemic segments at baseline were shown to be independently associated with a large response to BMC therapy. ConclusionThe present study demonstrates that diabetes and a large number of ischemic segments are predictors of a large response to intramyocardial BMC injection in refractory angina and chronic ischemia. Furthermore, the safety and efficacy results of previous trials are now confirmed in a larger study population.

Abstract 13: The PCI Choice Decision Aid for Stable Angina: A Randomized Trial.

Background: Although percutaneous coronary intervention (PCI) has not been shown to reduce the risk of death and myocardial infarction (MI) for stable coronary artery disease (CAD), many patients believe that PCI is a life-saving procedure. PCI for stable CAD is known to improve patients’ quality of life more rapidly than medications alone. We conducted a randomized trial to assess the impact of a decision aid (DA) compared to usual care (UC) for the treatment of stable CAD when there is a choice between PCI and optimal medical therapy (OMT). Methods: The PCI Choice trial was a prospective, randomized trial comparing the effects of DA versus UC. The DA was designed with a user-centered approach for an in-visit consultation, involving patients and clinicians throughout the development process. The final DA included information on myocardial infarction (MI), death and quality of life outcomes for PCI with OMT vs. OMT alone in the treatment of stable angina, stratified by angina type. Risks of procedure, bleeding, stent thrombosis, and need for future procedures were also depicted. The primary outcome was patient knowledge, measured by pre- and post-visit surveys. Additional outcomes included decisional conflict, patient satisfaction, preferred decision making style, and treatment decision. Results: A total of 110 patients were enrolled; mean age was 68.3 years and 26% of patients were women. At baseline, most patients had CCS Class I/II angina and were on a mean of two anti-anginal medications (2.3, SD 1.2). Knowledge increased among patients receiving DA compared to UC (63% vs. 44% p=0.0003). Specific knowledge about the impact of PCI for stable angina on death and MI was higher in both groups compared to prior studies (54% DA, 46% UC, p=0.45; 12% prior). Patient satisfaction was significantly higher in the DA group vs. UC (72% vs 40%, p=0.004). Decisional conflict was greater than in non-procedural DA trials, and was not different between the two arms (p=.43). Following exposure to DA, patients’ preference for sharing decision making tended to change more with DA (55% to 65%) than with UC (56% to 59%). While the proportion of patients choosing PCI over OMT was nearly half in both groups, there were fewer patients that remained undecided with DA (18% vs. 4%; p=0.14 overall difference). Conclusions: Exposure to a DA for the choice of PCI vs. optimal medical therapy in stable CAD improved patient knowledge and satisfaction and decreased uncertainty, without reducing the rate of PCI. Use of the DA in a larger patient population may further delineate impact on outcomes such as treatment choice, geographic variation and cost.

63 Effect of Preload Reduction on Left Ventricular Torsion in Patients with Heart Failure and Preserved Ejection Fraction on Maintenance Haemodialysis

BackgroundThe effects of dialysis on diastolic flow, short and long axis function have been previously studied. However its effect on left ventricle (LV) rotation and torsion is not known. LV...

Symptoms and Angiographic Findings of Patients Undergoing Elective Coronary Angiography Without Prior Stress Testing

Many patients undergo elective coronary angiography without preprocedural stress testing that may be suitable if performed in patients with more angina pectoris or more frequently identified obstructive coronary artery disease (CAD). Patients in the National Cardiovascular Data Registry CathPCI Registry undergoing elective coronary angiography from July 2009 to April 2013 were assessed for differences in angina (Canadian Cardiovascular Society [CCS] class) and severity of obstructive CAD in those with and without preprocedural stress testing, stratified by CAD history. Given the large sample size, differences were considered clinically meaningful if the standardized difference (SD) was >10%. Of 790,601 patients without CAD history, 36.9% did not undergo preprocedural stress testing. Compared with patients with preprocedural stress testing, patients without preprocedural stress testing were more frequently angina free (CCS class 0; 28.2% with stress test vs 38.5% without, SD= 14.8%) and had similar rates of obstructive CAD (40.1% with stress test vs 35.7% without, SD= 9.0). Of 449,579 patients with CAD history, 44.2% did not undergo preprocedural stress testing. Patients without preprocedural stress testing reported more angina (CCS class III/IV angina: 17.8% vs 13.4%; SD= 11.3%) but were not more likely to have obstructive CAD (78.7% vs 81.1%; SD= 5.8%) than patients with preprocedural stress testing. In conclusion, approximately 40% of patients undergoing elective coronary angiography did not have preprocedural risk stratification with stress testing. For these patients, the clinical decision to proceed directly to invasive evaluation was not driven primarily by severe angina and did not result in higher detection rates for obstructive CAD.

Long-term therapy with ivabradine in combination with beta-blockers in patients with stable angina pectoris and effect of beta-blocker background dose: results from the ADDITIONS 1-year follow-up

Objectives: The non-interventional multicenter ADDITIONS study follow-up evaluated the effectiveness, safety, and effect on quality of life (QoL) of ivabradine (iva) in combination with betablockers over one year. Methods: Resting heart rate (HR), the number of angina attacks, nitrate consumption, and concomitant medications were documented in 901 patients with chronic stable angina treated with iva twice daily in flexible doses in combination with betablockers for one year. QoL was evaluated by the EQ-5D patient questionnaire at each visit. A descriptive statistical analysis was performed. Results: 901 patients (intention to treat, mean age 65.4±10.6 years, 58% male) with chronic stable angina were analyzed. 53% of the patients had undergone a PCI or CABG before and 35% had a history of myocardial infarction. All patients received betablockers (e.g. Metoprolol 41%, mean daily dose (mdd) 109.6 mg; Bisoprolol 39%, mdd 6.9 mg; Nebivolol 13%, mdd 4.9 mg; Carvedilol 7%, mdd 28.9 mg) and concomitant standard medication. At baseline, most patients (49%) were classified CCS grade II, mean HR was 86.1±12.6 bpm, a mean of 1.7±2.2 angina attacks per week were reported, consumption of short-acting nitrates was 2.3±3.2 units per week, and the EQ-5D index was 0.66±0.28. After one year, iva (mean dose 12.53±2.84 mg per day) had reduced HR by 20.7±14.0 bpm to 65.4±8.8 bpm, the number of angina attacks by 1.4±2.5 per week (p<0.0001, Wilcoxon signed rank test), and nitrate consumption by 1.9±3.1 units per week (p<0.0001), had improved EQ-5D index by 0.18±0.27 (p<0.0001), and most patients (63%) were classified CCS grade I. HR reduction and improvement of angina symptoms by iva was similar in three subgroups defined by betablocker background dose (<50%, 50% to 99%, and ≥100% of recommended target dose): see table. View this table: Table 1 Conclusion: Over one year the combination of iva with betablockers in clinical practice not only effectively reduced HR, number of angina attacks, and nitrate consumption, but also improved QoL and CCS class in patients with stable angina. Moreover, the treatment effect of iva on HR and angina symptoms was independent of background betablocker dose.

FAME 2 global ischemic risk score and clinical outcome in patients with stable coronary disease receiving medical therapy alone

Purpose: We sought to investigate the relationship between global ischemia and clinical outcome in patients with stable coronary disease. Methods: This FAME 2 sub-analysis was conducted in 607 patients (pts) with at least one diseased major coronary artery, and receiving medical therapy (MT) alone (441 pts in the randomized trial and 166 pts with follow-up in the registry). We analyzed the rate of a composite of cardiovascular death, myocardial infarction, and ischemia-driven target lesion revascularization (MACE) in relation to a FAME 2 global ischemic risk score, defined as the sum of the individual risks of MACE for each target lesion and calculated as following: ∑1.3(1-FFRlesion)/0.05. Results: At least one MACE occurred in 95 pts (15.7%) at a median follow-up of 172 (80-284) days. Mean FAME 2 score was significantly higher in pts with MACE than in pts w/o MACE (16.2±18.7 vs. 9.4±12.1, p<0.0001). At multivariate Cox regression analysis (adjusted for age, hypertension, hypercholesterolemia, CCS class, silent ischemia and the number of vessel disease), FAME 2 score as a continuous variable was significantly associated with MACE (p=0.001, HR [95% CI]: 1.019 [0.008-0.030]). Kaplan-Meier analysis of 1-year MACE-free survival showed a significant difference between the three tertiles of the FAME 2 score (Log-rank 32.88, p<0.0001). Taking into account the localization of the stenotic segment, as weighted by the Leaman score, did not improve the predictive value of the FAME 2 score for MACE. Conclusions: The FAME 2 global ischemic risk score is an independent predictor of clinical outcome at 1-year follow-up. The data also suggest that, in the short term, the severity of ischemia (depth) is prognostically more important than its extent (breadth).

Prognosis in 10 years of follow-up of three therapeutic strategies for chronic multivessel coronary artery disease in women (study MASS)

Studies were contradictory regarding increased mortality in women undergoing coronary interventions. The worst prognosis in women was justified by aging, body mass index and more comorbidity. The aim of this study was to analyze the long-term prognosis of each therapeutic strategy, Coronary Artery Bypass Graft (CABG), Percutaneous Coronary Intervention (PCI) and Medical Treatment (MT) in men and women. Methods: A prospective 10-year follow-up study randomized 1084 patients with stable chronic CAD for MT (N=324, 30%), PCI (N=306, 28%) or CABG (N=454, 42%). The number of women for each strategy was respectively: 100 (9%), 97 (9%) and 116 (10%). CAD was defined by the presence of angina pectoris CCS class II and III, positive exercise stress testing, ejection fraction >40% and ≥2 coronary lesions >70%. Primary outcomes were incidence of total mortality, Q-MI, or refractory angina that required revascularization. All data were analyzed according to the intention-to-treat principle. Results: Women had a higher number of primary events with the CABG strategy (p=0.002) and similar to the MT (p=0.902) and ICP (p=0.465), however the CABG was the best therapeutic strategy in women (Figure 1). To death, no differences were observed for both sexes in all strategies (Figure 2). In multivariate Cox regression sex was not an independent variable for each strategy for both primary events and death. For primary events independent variables for poor outcome for each strategy were: PCI, diabetes (p = 0.030); MT, hypertension (p=0.006); CABG, age (p<0.001). To death, were: PCI, no variable; MT, age (p=0.011) and diabetes (p=0.030); CABG, age (p<0.001). ![Figure][1] Conclusion: CABG was the best treatment strategy in women despite the higher number of primary events compared with men. [1]: pending:yes

Echo-guided extracorporeal shock wave therapy for refractory angina improves regional myocardial blood flow as assessed by PET imaging

Purpose: Low-intensity extracorporeal shock wave (SW) therapy (SWT) has been shown to improve symptoms and exercise tolerance in patients (pts.) with coronary artery disease (CAD) not suitable for conventional revascularization strategies. Induction of neovascularization and improvement of myocardial perfusion are mechanisms hypothetized to be involved. Methods: 43 pts. with advanced CAD (mean age 67±10 years) not suitable for catheter-based or surgical revascularization were suffering from severe stable angina pectoris (CCS class III or IV) refractory to individually optimized medical treatment underwent a series of 9 echocardiography-targeted SW applications (3 SW applications/week during weeks 1, 5, and 9). The antero-septal wall (LAD territory) was targeted in 19, the lateral wall (RCX territory) in 18, and the inferior wall (RCA territory) in 6 pts. A series of 300-500 shock waves was applied per session. Anti-anginal medication (combination of 2 or 3 drugs) was kept unchanged. Regional myocardial blood flow (MBF) was measured quantitatively by NH3-PET at baseline and 4-6 weeks after completion of SWT. Results: Complications of SWT did not occur, markers of myocardial cell damage were all negative during SWT. At follow-up, 30 pts. (64%) reported improvement of angina to a tolerable level. CCS angina class decreased from 3.1±0.6 to 2.5±0.6 (p<0.0001). Maximum ergometric workload increased from 78±53 to 90±46 watts (p=0.04). MBF in the LV region targeted by SWT improved from 119+42 mL/min/100g at baseline to 129±48 mL/min/100g at follow up (p=0.047), while there was no change in the opposite wall (136±52 vs. 137±53 ml/min/100g; p=0.9). Conclusions: SWT improves symptoms in a sizeable number of pts. with chronic refractory angina. Regional improvement of MBF in the region targeted by SWT was also documented by PET imaging. Additional studies are warranted to clarify the role of SWT in the armamentarium for this challenging patient group.