Rainer Zbinden

Beneficial Effect of Recruitable Collaterals A 10-Year Follow-Up Study in Patients With Stable Coronary Artery Disease Undergoing Quantitative Collateral Measurements

Background— The prognostic relevance of the collateral circulation is still controversial. The goal of this study was to assess the impact on survival of quantitatively obtained, recruitable coronary collateral flow in patients with stable coronary artery disease during 10 years of follow-up. Methods and Results— Eight-hundred forty-five individuals (age, 62±11 years), 106 patients without coronary artery disease and 739 patients with chronic stable coronary artery disease, underwent a total of 1053 quantitative, coronary pressure–derived collateral measurements between March 1996 and April 2006. All patients were prospectively included in a collateral flow index (CFI) database containing information on recruitable collateral flow parameters obtained during a 1-minute coronary balloon occlusion. CFI was calculated as follows: where Poccl is mean coronary occlusive pressure, Pao is mean aortic pressure, and CVP is central venous pressure. Patients were divided into groups with poorly developed (CFI <0.25) or well-grown collateral vessels (CFI ≥0.25). Follow-up information on the occurrence of all-cause mortality and major adverse cardiac events after study inclusion was collected. Cumulative 10-year survival rates in relation to all-cause deaths and cardiac deaths were 71% and 88%, respectively, in patients with low CFI and 89% and 97% in the group with high CFI (P=0.0395, P=0.0109). Through the use of Cox proportional hazards analysis, the following variables independently predicted elevated cardiac mortality: age, low CFI (as a continuous variable), and current smoking. Conclusions— A well-functioning coronary collateral circulation saves lives in patients with chronic stable coronary artery disease. Depending on the exact amount of collateral flow recruitable during a brief coronary occlusion, long-term cardiac mortality is reduced to one fourth compared with the situation without collateral supply.

Randomized Comparison of a Titanium-Nitride-Oxide–Coated Stent With a Stainless Steel Stent for Coronary Revascularization The TiNOX Trial

Background—Stent coating with titanium-nitride-oxide has been shown to reduce neointimal hyperplasia in the porcine restenosis model. We designed a prospective, randomized, clinical study to investigate the safety and efficacy of titanium-nitride-oxide–coated stents compared with stainless steel stents. Methods and Results—Ninety-two patients with de novo lesions were randomly assigned to treatment with titanium-nitride-oxide–coated stents (n=45) or stainless steel stents of otherwise identical design (n=47; control). Baseline characteristics were similar in both groups. At 30 days, no stent thromboses or other adverse events had occurred in either group. Quantitative coronary angiography at 6 months revealed lower late loss (0.55±0.63 versus 0.90±0.76 mm, P=0.03) and percent diameter stenosis (26±17% versus 36±24%, P=0.04) in lesions treated with titanium-nitride oxide–coated than in control stents. Binary restenosis was reduced from 33% in the control group to 15% in the titanium-nitride oxide–coated stent group (P=0.07). Intravascular ultrasound studies at 6 months showed smaller neointimal volume in titanium-nitride-oxide–coated stents than in control stents (18±21 versus 48±28 mm3, P<0.0001). Major adverse cardiac events at 6 months were less frequent in titanium-nitride-oxide–coated stents than in control stent–treated patients (7% versus 27%, P=0.02), largely driven by a reduced need for target-lesion revascularization (7% versus 23%, P=0.07). Conclusions—Revascularization with titanium-nitride-oxide–coated stents is safe and effective in patients with de novo native coronary artery lesions. Titanium-nitride-oxide–coated stents reduce restenosis and major adverse cardiac events compared with stainless steel stents of otherwise identical design.

Coronary collateral flow in response to endurance exercise training.

Background In humans, it is not known whether physical endurance exercise training promotes coronary collateral growth. The following hypotheses were tested: the expected collateral flow reduction after percutaneous coronary intervention of a stenotic lesion is prevented by endurance exercise training; collateral flow supplied to an angiographically normal coronary artery improves in response to exercise training; there is a direct relationship between the change of fitness after training and the coronary collateral flow change. Methods and results Forty patients (age 61 ± 8 years) underwent a 3-month endurance exercise training program with baseline and follow-up assessments of coronary collateral flow. Patients were divided into an exercise training group (n = 24) and a sedentary group (n = 16) according to the fact whether they adhered or not to the prescribed exercise program, and whether or not they showed increased endurance (V o 2max in ml/min per kg) and performance (W/kg) during follow-up versus baseline bicycle spiroergometry. Collateral flow index (no unit) was obtained using pressure sensor guidewires positioned in the coronary artery undergoing percutaneous coronary intervention and in a normal vessel. In the vessel initially undergoing percutaneous coronary intervention, there was an increase in collateral flow index among exercising but not sedentary patients from 0.155 ± 0.081 to 0.204 ± 0.056 (P=0.03) and from 0.189 ± 0.084 to 0.212 ± 0.077 (NS), respectively. In the normal vessel, collateral flow index changes were from 0.176 ± 0.075 to 0.227 ± 0.070 in the exercise group (P=0.0002), and from 0.219 ± 0.103 to 0.238 ± 0.086 in the sedentary group (NS). A direct correlation existed between the change in collateral flow index from baseline to follow-up and the respective alteration of V o 2max (P=0.007) and Watt (P=0.03). Conclusion A 3-month endurance exercise training program augments coronary collateral supply to normal vessels, and even to previously stenotic arteries having undergone percutaneous coronary intervention before initiating the program. There appears to be a dose–response relation between coronary collateral flow augmentation and exercise capacity gained.

Patent foramen ovale closure in recreational divers: effect on decompression illness and ischaemic brain lesions during long-term follow-up

Objective To test the effect of patent foramen ovale (PFO) closure on neurological events in divers. Design Prospective, non-randomised, longitudinal three-arm study. Setting Tertiary referral centre. Population 104 scuba divers with a history of major decompression illness (DCI). Intervention Transcutaneous PFO closure. Main outcome measures Baseline and three follow-up examinations with a questionnaire about health status and diving habits/accidents, transoesophageal echocardiography at baseline for PFO grading, cerebral MRI at all examinations. Results 39 divers had no PFO, 26 had a PFO and chose to undergo percutaneous closure and 39 had a PFO, but decided not to undergo closure. The total number of dives, including those performed before baseline and those during long-term follow-up, was 81 654; 18 394 dives during the follow-up period of 5.3±0.3 years, during which there were a total of five major neurological DCI events–namely 0 in the no PFO group, 0.5±2.5/104 dives in the PFO closure group and 35.8±102.5/104 dives in the PFO no closure group (four events; p=0.045 between the PFO groups). In the groups, no PFO, PFO closure and PFO no closure, there were 1.1±2.6, 0.8±1.4, 3.3±6.9 ischaemic brain lesions, respectively, at follow-up (p=0.039 between the PFO groups)—that is, 16±42/104 dives in the no PFO group, 6±13/104 dives in the PFO closure group and 104±246/104 dives in the PFO no closure group (overall p=0.042; p=0.024 between the PFO groups). Conclusion PFO closure in continuing divers appears to prevent symptomatic (major DCI) and asymptomatic (ischaemic brain lesions) neurological events during long-term follow-up.

An indicator of sudden cardiac death during brief coronary occlusion: electrocardiogram QT time and the role of collaterals.

AIMS The coronary collateral circulation has a beneficial role regarding all-cause and cardiac mortality. Hitherto, the underlying mechanism has not been clarified. The aim of this prospective study was to assess the effect of the coronary collateral circulation on electrocardiogram (ECG) QTc time change during short-term myocardial ischaemia. METHODS AND RESULTS A total of 150 patients (mean age 63 +/- 11 years, 38 women) were prospectively included in this study. An ECG was recorded at baseline and during a standardized 1 min coronary balloon occlusion. QT interval was measured before, during, and after balloon occlusion and was corrected for heart rate (QTc). Simultaneously obtained collateral flow index (CFI), expressing collateral flow relative to normal anterograde flow, was determined based on intracoronary pressure measurements. During occlusion of the left anterior descending coronary artery mean QTc interval increased from 422 +/- 33 to 439 +/- 36 ms (P < 0.001), left circumflex occlusion led to an increase from 414 +/- 32 to 427 +/- 27 ms (P < 0.001). QTc was not influenced by occlusion of the right coronary artery (RCA) (417 +/- 35 and 415 +/- 34 ms, respectively; P = 0.863). QTc change during occlusion of the left coronary artery was inversely correlated with CFI (R(2) = 0.122, P = 0.0002). CONCLUSION Myocardial ischaemia leads to QT prolongation during a controlled 1 min occlusion of the left, but not the RCA. QT prolongation is inversely related to collateral function indicating a protective mechanism of human coronary collaterals against cardiac death.

Influence of diabetes mellitus on coronary collateral flow: an answer to an old controversy

Objectives: To determine the influence of diabetes mellitus on coronary collateral flow by accurate means of collateral flow measurement in a large population with variable degrees of coronary artery disease. Methods: 200 patients (mean (SD) age 64 (9) years; 100 diabetic and 100 non-diabetic) were enrolled in the study. Coronary collateral flow was assessed in 174 stenotic and in 26 angiographically normal vessels with a pressure guidewire (n  =  131), Doppler guidewire (n  =  36), or both (n  =  33) to calculate pressure or flow velocity derived collateral flow index (CFI). Diabetic patients were perfectly matched with a non-diabetic control group for clinical, haemodynamic, and angiographic parameters. Results: CFI did not differ between the diabetic and the non-diabetic patients (0.21 (0.12) v 0.19 (0.13), not significant). Likewise, CFI did not differ when only angiographically normal vessels (0.20 (0.09) v 0.15 (0.08), not significant) or chronic total coronary occlusions (0.30 (0.14) v 0.30 (0.17), not significant) were compared. Fewer patients in the diabetic group tended to have angina pectoris during the one minute vessel occlusion (60 diabetic v 69 non-diabetic patients, p  =  0.15). Conclusion: Quantitatively measured coronary CFI did not differ between diabetic and non-diabetic patients with stable coronary artery disease.

Non-invasive gene-expression-based detection of well-developed collateral function in individuals with and without coronary artery disease

Background: In patients with coronary artery disease (CAD), a well grown collateral circulation has been shown to be important. The aim of this prospective study using peripheral blood monocytes was to identify marker genes for an extensively grown coronary collateral circulation. Methods: Collateral flow index (CFI) was obtained invasively by angioplasty pressure sensor guidewire in 160 individuals (110 patients with CAD, and 50 individuals without CAD). RNA was extracted from monocytes followed by microarray-based gene-expression analysis. 76 selected genes were analysed by real-time polymerase chain reaction (PCR). A receiver operating characteristics analysis based on differential gene expression was then performed to separate individuals with poor (CFI<0.21) and well-developed collaterals (CFI⩾0.21) Thereafter, the influence of the chemokine MCP-1 on the expression of six selected genes was tested by PCR. Results: The expression of 203 genes significantly correlated with CFI (p = 0.000002–0.00267) in patients with CAD and 56 genes in individuals without CAD (p = 00079–0.0430). Biological pathway analysis revealed 76 of those genes belonging to four different pathways: angiogenesis, integrin-, platelet-derived growth factor-, and transforming growth factor β-signalling. Three genes in each subgroup differentiated with high specificity among individuals with low and high CFI (⩾0.21). Two out of these genes showed pronounced differential expression between the two groups after cell stimulation with MCP-1. Conclusions: Genetic factors play a role in the formation and the preformation of the coronary collateral circulation. Gene expression analysis in peripheral blood monocytes can be used for non-invasive differentiation between individuals with poorly and with well grown collaterals. MCP-1 can influence the arteriogenic potential of monocytes.

Ultrathin Strut Biodegradable Polymer Sirolimus‐Eluting Stent Versus Durable‐Polymer Everolimus‐Eluting Stent for Percutaneous Coronary Revascularization: 2‐Year Results of the BIOSCIENCE Trial

Background No data are available on the long‐term performance of ultrathin strut biodegradable polymer sirolimus‐eluting stents (BP‐SES). We reported 2‐year clinical outcomes of the BIOSCIENCE (Ultrathin Strut Biodegradable Polymer Sirolimus‐Eluting Stent Versus Durable Polymer Everolimus‐Eluting Stent for Percutaneous Coronary Revascularisation) trial, which compared BP‐SES with durable‐polymer everolimus‐eluting stents (DP‐EES) in patients undergoing percutaneous coronary intervention. Methods and Results A total of 2119 patients with minimal exclusion criteria were assigned to treatment with BP‐SES (n=1063) or DP‐EES (n=1056). Follow‐up at 2 years was available for 2048 patients (97%). The primary end point was target‐lesion failure, a composite of cardiac death, target‐vessel myocardial infarction, or clinically indicated target‐lesion revascularization. At 2 years, target‐lesion failure occurred in 107 patients (10.5%) in the BP‐SES arm and 107 patients (10.4%) in the DP‐EES arm (risk ratio [RR] 1.00, 95% CI 0.77–1.31, P=0.979). There were no significant differences between BP‐SES and DP‐EES with respect to cardiac death (RR 1.01, 95% CI 0.62–1.63, P=0.984), target‐vessel myocardial infarction (RR 0.91, 95% CI 0.60–1.39, P=0.669), target‐lesion revascularization (RR 1.17, 95% CI 0.81–1.71, P=0.403), and definite stent thrombosis (RR 1.38, 95% CI 0.56–3.44, P=0.485). There were 2 cases (0.2%) of definite very late stent thrombosis in the BP‐SES arm and 4 cases (0.4%) in the DP‐EES arm (P=0.423). In the prespecified subgroup of patients with ST‐segment elevation myocardial infarction, BP‐SES was associated with a lower risk of target‐lesion failure compared with DP‐EES (RR 0.48, 95% CI 0.23–0.99, P=0.043, P interaction=0.026). Conclusions Comparable safety and efficacy profiles of BP‐SES and DP‐EES were maintained throughout 2 years of follow‐up. Clinical Trial Registration URL: https://www.clinicaltrials.gov. Unique identifier: NCT01443104.

Myocardial Blood Volume and Coronary Resistance During and After Coronary Angioplasty

Animal experiments have shown that the coronary circulation is pressure distensible, i.e., myocardial blood volume (MBV) increases with perfusion pressure. In humans, however, corresponding measurements are lacking so far. We sought to quantify parameters reflecting coronary distensibility such as MBV and coronary resistance (CR) during and after coronary angioplasty. Thirty patients with stable coronary artery disease underwent simultaneous coronary perfusion pressure assessment and myocardial contrast echocardiography (MCE) of 37 coronary arteries and their territories during and after angioplasty. MCE yielded MBV and myocardial blood flow (MBF; in ml · min(-1) · g(-1)). Complete data sets were obtained in 32 coronary arteries and their territories from 26 patients. During angioplasty, perfusion pressure, i.e., coronary occlusive pressure, and MBV varied between 9 and 57 mmHg (26.9 ± 11.9 mmHg) and between 1.2 and 14.5 ml/100 g (6.7 ± 3.7 ml/100 g), respectively. After successful angioplasty, perfusion pressure and MBV increased significantly (P < 0.001 for both) and varied between 64 and 118 mmHg (93.5 ± 12.8 mmHg) and between 3.7 and 17.3 ml/100 g (9.8 ± 3.4 ml/100 g), respectively. Mean MBF increased from 31 ± 20 ml · min(-1) · g(-1) during coronary occlusion, reflecting collateral flow, to 121 ± 33 ml · min(-1) · g(-1) (P < 0.01), whereas mean CR, i.e., the ratio of perfusion pressure and MBF, decreased by 20% (P < 0.001). In conclusion, the human coronary circulation is pressure distensible. MCE allows for the quantification of CR and MBV in humans.

Silent ischemia normalized for coronary collateral function in patients with and without diabetes mellitus

failure mainly due to post rheumatic valvulopathies in young patients in our centre. A national program for fight against rheumatic fever and complications is of great urgency in our country. The compensation treatment of congestive heart failure is challenging in our milieu, characterized by poor compliance and financial limitation. The authors of this manuscript have certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology [5]. Special thanks to the Tertiairy Sisters of Saint Francis for their devotion in the management of the cardiac centre. References