Psychosocial distress and health status as risk factors for ten-year major adverse cardiac events and mortality in patients with non-obstructive coronary artery disease.

BACKGROUND: We examined the risk of psychosocial distress, including Type D personality, depressive symptoms, anxiety, positive mood, hostility, and health status fatigue and disease specific and generic quality of life for MACE in patients with non-obstructive coronary artery disease (NOCAD). METHODS: In the Tweesteden mild stenosis (TWIST) study, 546 patients with NOCAD were followed for 10 years to examine the occurrence of cardiac mortality, a major cardiac event, or non-cardiac mortality in the absence of a cardiac event. Cox proportional hazard models were used to examine the impact of psychosocial distress and health status on the occurrence of MACE while adjusting for age, sex, disease severity, and lifestyle covariates. RESULTS: In total 19% of the patients (mean age baseline = 61, SD 9 years; 52% women) experienced MACE, with a lower risk for women compared to men. Positive mood (HR 0.97, 95%CI 0.95-1.00), fatigue (HR 1.03, 95%CI 1.00-1.06), and physical limitation (HR 0.99, 95%CI 0.98-1.00) were associated with MACE in adjusted models. No significant interactions between sex and psychosocial factors were present. Depressive symptoms were predictive of MACE, but no longer after adjustment. CONCLUSIONS: In patients with NOCAD fatigue, low positive mood, and a lower physical limitation score were associated with MACE, without marked sex differences. Type D personality, psychosocial factors, and health status were not predictive of adverse outcomes. Reducing psychosocial distress is a valid intervention goal by itself, though it is less likely to affect MACE in patients with NOCAD.

Intra-aortic balloon pump counterpulsation in extensive myocardial infarction with persistent ischemia: The SEMPER FI pilot study.

OBJECTIVES: This study aimed to prospectively investigate intra-aortic balloon pump counterpulsation (IABP) support in large myocardial infarction complicated by persistent ischemia after primary percutaneous coronary intervention (PCI). BACKGROUND: Use of IABP is suggested to be effective by increasing diastolic aortic pressure, thereby improving coronary blood flow. This can only be expected with exhausted coronary autoregulation, typical in acute myocardial infarction complicated by persistent ischemia. In this situation, augmented diastolic pressure is expected to increase myocardial oxygenation. METHODS: One hundred patients with large STEMI complicated by persistent ischemia after primary PCI were randomized to treatment with or without IABP therapy on top of standard care. IABP support was initiated following primary PCI, immediately after inclusion. Primary end point was all-cause mortality, need for (additional) mechanical hemodynamic support, or readmission for heart failure within 6 months. RESULTS: Mean age was 63 ± 10 years, 76% were male. Mean systolic and diastolic blood pressure were 120 ± 25 mmHg and 73 ± 17 mmHg. Mean heart rate was 75 ± 18 mmHg. Before PCI, mean summed ST-deviation was 21 ± 8 mm with only minimal ST-resolution after PCI. One patient in the IABP group reached the primary end point versus four patients in the control group (2% vs. 8%; p = 0.16). After primary PCI, resolution of ST-deviation was significantly more pronounced in the IABP group (73 ± 17%) compared to the control group (56 ± 26%; p < 0.01). CONCLUSIONS: In this pilot study, in patients with large STEMI and persistent ischemia after primary PCI, use of IABP showed a nonsignificant decrease in mortality, necessity for (additional) mechanical hemodynamic support or readmission for heart failure at 6 months, and resulted in more rapid ST-resolution.

The predictive value of positive affect and Type D personality for adverse cardiovascular clinical outcomes in patients with non-obstructive coronary artery disease.

BACKGROUND: Patients with non-obstructive coronary artery disease (NOCAD) continue to experience disabling symptoms. Positive affect (PA) has shown a cardioprotective potential. Type D personality has previously been shown to have a deleterious effect on adverse outcomes in diverse cardiac populations. Little is known about the predictive value of PA and Type D personality for long-term outcomes in NOCAD patients. The aim was to investigate the effect of PA and Type D personality on clinical outcomes. METHODS: 547 patients (mean age 61 years±9, 48% male) who underwent a coronary angiography or CT-scan between January 2009 and February 2013 answered questionnaires concerning PA (GMS) and Type D personality (DS14). Cox proportional hazards analyses were performed. RESULTS: When analyzed dichotomously, PA was a significant predictor of need for repeat cardiac testing (HR=0.64, 95% CI: 0.41-0.99), but not emergency department (ED) admissions (HR=0.83, 95% CI: 0.52-1.32) after adjustment for age, sex, education, diagnosis by group, BMI and hypertension. Analyzed continuously, the predictive value of PA was non-significant for both repeat testing (HR=0.85, 95% CI: 0.69-1.06) and ED admissions (HR=0.98, 95% CI: 0.77-1.23). Type D personality, both continuously and dichotomously, was not significantly associated with the outcomes. Findings were also examined for men and women separately. CONCLUSION: Although Type D personality was not predictive of adverse events in this sample, PA is an interesting and important variable to take into account in NOCAD patients. Research on psychosocial factors in NOCAD patients should consider the importance of choices of endpoint, given the heterogeneity of NOCAD patients.

Impaired Health Status, Psychological Distress, and Personality in Women and Men With Nonobstructive Coronary Artery Disease: Sex and Gender Differences: The TWIST (Tweesteden Mild Stenosis) Study.

BACKGROUND: Patients with nonobstructive coronary artery disease (NOCAD; wall irregularities, stenosis <60%), and women with NOCAD in particular, remain underinvestigated. We examined sex and gender (S&G) differences in health status, psychological distress, and personality between patients with NOCAD and the general population, as well as S&G differences within the NOCAD population. METHODS AND RESULTS: In total, 523 patients with NOCAD (61±9 years, 52% women) were included via coronary angiography and computed tomography as part of the TWIST (Tweesteden Mild Stenosis) study. Generic health status (12-item Short Form physical and mental scales and fatigue), psychological distress (Hospital Anxiety and Depression Scale anxiety and depressive symptoms and Global Mood Scale negative and positive affect), and personality (Type D personality) were compared between patients with NOCAD and an age- and sex-matched group of 1347 people from the general population. Frequency matching was performed to obtain a similar sex distribution in each age-decile group. Both men and women with NOCAD reported impaired health status, more psychological distress, and Type D personality compared with men and women in the reference group. Women reported more psychosocial distress compared with men, but no significant sex-by-group interaction effects were observed. Women with NOCAD reported impaired health status, more anxiety, and less positive affect, but no differences in depressive symptoms, angina, or Type D personality when compared with men with NOCAD. Age, education, employment, partner, and alcohol use explained these S&G differences within the NOCAD group. CONCLUSIONS: In both men and women, NOCAD was associated with impaired health status, more psychological distress, and Type D personality when compared with a reference population. Factors reflecting S&G differences explained these S&G findings in patient-reported outcomes. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01788241.

C-reactive protein and fibrinogen in non-obstructive coronary artery disease as related to depressive symptoms and anxiety: findings from the TweeSteden Mild Stenosis Study (TWIST).

OBJECTIVE: The majority of acute coronary syndromes occur in the absence of obstructive coronary artery disease (CAD), and the underlying biobehavioral processes are not well understood. Depressive symptoms and anxiety are predictive of prognosis, and have been associated with markers of inflammation that play a role in atherosclerosis. This study examines whether depressive symptoms and anxiety are associated with higher levels of high-sensitive C-reactive protein (hs-CRP) and fibrinogen in patients with non-obstructive CAD. METHODS: Patients with non-obstructive CAD ("wall irregularities", stenosis<60%, N=414, mean age 62.1 ± 9.3 years, 52% women) in the TweeSteden Mild Stenosis (TWIST) observational cohort study completed the Hospital Anxiety and Depression Scale (HADS). Blood samples were analyzed for hs-CRP and fibrinogen. The cross-sectional association of anxiety and depressive symptoms with hs-CRP and fibrinogen, adjusting for covariates, was examined by multivariate regression analysis. RESULTS: Depressive symptoms were positively associated with hs-CRP level (ß=.135, p=.009), but not fibrinogen (ß=.075, p=.153), adjusted for age and sex. Additional adjustments for sociodemographic, disease severity and lifestyle factors rendered the association non-significant. In the fully adjusted model, depressive symptoms were not associated with hs-CRP (ß=.036, p>0.10) and BMI was the only variable that was independently associated with hs-CRP (ß=.203, p<.001). No associations were observed for anxiety with either hs-CRP or fibrinogen (p>0.10). CONCLUSION: Among patients with non-obstructive CAD, depressive symptoms and anxiety were not independently associated with hs-CRP and fibrinogen.

Type D personality and patient-perceived health in nonsignificant coronary artery disease: the TWeesteden mIld STenosis (TWIST) study.

PURPOSE: To examine whether Type D--distressed--personality is independently associated with patient reported health outcomes, such as chest pain, health status and emotional distress, in patients with angiographically nonsignificant coronary abnormalities. Psychosocial factors, such as Type D personality, are risk factors for established coronary artery disease (CAD), but are unknown for patients with non-obstructive CAD. METHODS: A total of 273 patients (62 years, SD 10, 49 % male) participated in the cross-sectional part of the 'TWeesteden mIld STenosis' study. Inclusion was based on coronary angiography or CT-scan. Type D personality was examined in relation to chest pain, disease-specific (Seattle Angina Questionnaire) and generic health status (Short Form 12), and emotional distress (Hospital Anxiety and Depression Scale, Fatigue), adjusted for confounders and potential explanatory lifestyle factors. RESULTS: Patients with Type D personality (30 %) had an increased prevalence of chest pain (57 vs. 40 %). When adjusted for confounder's age, gender, comorbidity, and medication use, Type D personality was significantly associated with increased chest pain, poorer disease-specific and generic health status and increased emotional distress. After further adjustment for explanatory lifestyle factors such as smoking, physical activity, and metabolic syndrome, Type D personality was associated with worse disease perception, lower treatment satisfaction, poor physical and mental health status, and higher emotional distress, but no longer with chest pain, angina stability, or physical limitations. CONCLUSION: Type D personality was significantly associated with poor patient-perceived symptoms in patients with mild coronary abnormalities, which can be hypothesized to be detrimental in the long run.

Quantitative assessment of coronary microvascular function in patients with and without epicardial atherosclerosis.

AIMS: The influence of atherosclerosis and its risk factors on coronary microvascular function remain unclear as current methods of assessing microvascular function do not specifically test the microcirculation in isolation. We examined the influence of epicardial vessel atherosclerosis on coronary microvascular function using the index of myocardial resistance (IMR). METHODS AND RESULTS: IMR (a measure of microvascular function) and fractional flow reserve (FFR, a measure of the epicardial compartment) were measured in 143 coronary arteries (116 patients). Fifteen patients (22 arteries, mean age 48+/-16 years) had no clinical evidence of atherosclerosis (control group). One hundred and one patients (121 arteries, mean age 63+/-11 years) had established atherosclerosis and multiple cardiovascular risk factors (atheroma group). Mean IMR in the control group (19+/-5, range 8-28) was significantly lower than in the atheroma group (25+/-13, range 6-75) (P<0.01). However, there was large overlap between IMR in both groups, with 69% of IMR values in patients with atheroma being within the control range. Mean FFR was also higher in the control group (0.96+/-0.02, range 0.93-1.00) than in the atheroma group (0.85+/-0.14, range 0.19-1.00) (P<0.01). There was no correlation between IMR and FFR (r=0.09; P=0.24), even when results in the control (r=0.02; P=0.92) and atheroma (r=0.15; P=0.10) groups were analysed in isolation. Using stepwise multiple regression analysis presence/absence of atheroma (ss=0.42; P=0.02) was the only independent determinant of IMR. CONCLUSIONS: Mean IMR is higher in patients with epicardial atherosclerosis. However, there is a large overlap between IMR in patients with and without epicardial atherosclerosis.

Continuous infusion thermodilution for assessment of coronary flow: theoretical background and in vitro validation.

Direct volumetric assessment of coronary flow during cardiac catheterization has not been available so far. In the current study continuous infusion thermodilution, a method based on continuous infusion of saline into a selective coronary artery is evaluated. Theoretically, volumetric flow can be calculated from the known infusion rate (Q(i)), the temperatures of the blood (T(b)), the saline (T(i)), and the mixture downstream to the infusion site (T). We aimed to validate and optimize the measurement method in an in vitro model of the coronary circulation. Full mixing of infusate and blood was found to be the main prerequisite for accurate determination of the coronary flow. To achieve full mixing the influence of catheter design, infusion rate, and location of temperature measurement were assessed. We found that continuous infusion thermodilution slightly overestimated coronary flow determined by directly measured reference flow by 7+/-8%, over the entire physiological flow range of 50-250 ml/min. These results were found using a specially designed infusion catheter (infusion mainly through distally located sideholes), a high enough infusion rate (25 ml/min), and measurement of the mixing temperature between 5 and 8 cm distal from the tip of the infusion catheter. Absolute coronary flow rate can be measured reliably by the continuous infusion method when full mixing is present, under the conditions mentioned above.

Direct volumetric blood flow measurement in coronary arteries by thermodilution.

OBJECTIVES: This study sought to validate a new method for direct volumetric blood flow measurement in coronary arteries in animals and in conscious humans during cardiac catheterization. BACKGROUND: Direct volumetric measurement of blood flow in selective coronary arteries would be useful for studying the coronary circulation. METHODS: Based on the principle of thermodilution with continuous low-rate infusion of saline at room temperature, we designed an instrumental setup for direct flow measurement during cardiac catheterization. A 2.8-F infusion catheter and a standard 0.014-inch sensor-tipped pressure/temperature guidewire were used to calculate absolute flow (Q(thermo)) in a coronary artery from the infusion rate of saline, temperature of the saline at the tip of the infusion catheter, and distal blood temperature during infusion. The method was tested over a wide range of flow rates in 5 chronically instrumented dogs and in 35 patients referred for physiological assessment of a coronary stenosis or for percutaneous coronary intervention. RESULTS: Thermodilution-derived flow corresponded well with true flow (Q) in all dogs (Q(thermo) = 0.73 Q + 42 ml/min; R(2) = 0.72). Reproducibility was excellent (Q(thermo,)(1) = 0.96 x Q(thermo,)(2) + 3 ml/min; R(2) = 0.89). The measurements were independent of infusion rate and sensor position as predicted by theory. In the humans, a good agreement was found between increase of thermodilution-derived volumetric blood flow after percutaneous coronary intervention and increase of fractional flow reserve (R(2) = 0.84); reproducibility of the measurements was excellent (Q(thermo,)(1) = 1.0 Q(thermo,)(2) + 0.9 ml/min, R(2) = 0.97), and the measurements were independent of infusion rate and sensor position. CONCLUSIONS: Using a suitable infusion catheter and a 0.014-inch sensor-tipped guidewire for measurement of coronary pressure and temperature, volumetric blood flow can be directly measured in selective coronary arteries during cardiac catheterization.

Acute myocardial infarction and underlying stenosis severity.

OBJECTIVES: The objective of this study was to investigate the underlying stenosis severity of the culprit lesion in acute myocardial infarction. BACKGROUND: It is widely believed that myocardial infarction often occurs in angiographically mild luminal stenosis. This, however, is in contradiction with experience from interventional practice in primary PCI. METHODS: We performed quantitative coronary angiography (QCA) in 250 consecutive patients referred for acute percutaneous coronary intervention (PCI) because of acute myocardial infarction (AMI). Fundamental for analysis was that a realistic estimate of underlying luminal narrowing before the infarction could be made angiographically that QCA could be performed and that one of two criteria was met: (1) spontaneous reflow allowing assessment of the lumen proximal and distal to the culprit lesion, or (2) coronary artery closed at arrival but reflow after uncomplicated wiring allowing assessment of the lumen proximal and distal to the culprit lesion. RESULTS: Of 250 consecutive patients (mean age 61.7 +/- 12.7 years, 48 women) referred for acute PCI, 156 patients (62%) fulfilled at least one of the above criteria for reliable QCA. In 151 of these patients (96%) the severity of the underlying stenosis was >50% and in 103 (66%) it was >70%. There were no differences in stenosis severity between the left anterior descending [LAD, (72 +/- 13)%, n = 57], left circumflex [Cx, (74 +/- 10)%, n = 20], and right coronary artery territory [RCA, (74 +/- 12)%, n = 76] (ANOVA, P = 0.76). There were no differences in stenosis severity between women [(73 +/- 13)%, n = 36] and men [(75 +/- 11)%, n = 120; P = 0.35]. CONCLUSION: In contrast to what is often believed, the majority of myocardial infarctions occurs in significant stenosis.

Determinants of coronary steal in chronic total coronary occlusions donor artery, collateral, and microvascular resistance.

OBJECTIVES: We aimed to assess the mechanisms of coronary steal by direct hemodynamic measurements of the collateral circulation in chronic total coronary occlusions (CTO). BACKGROUND: Coronary steal may cause ischemia despite well-developed collaterals in coronary artery disease. METHODS: Fifty-six patients were studied during recanalization of a CTO. Before recanalization, the fractional flow reserve in the donor artery (FFR(D)) at the takeoff of the collaterals and the coronary flow reserve were recorded. After crossing the occlusion, the distal coronary flow velocity was measured by a Doppler wire (APV(Occl)), and distal pressure by a pressure wire. Changes of these parameters were assessed during intravenous adenosine (140 microg/kg/min). Resistance indexes for the donor artery (R(D)), collaterals (R(C)), and microcirculation (R(P)) were calculated. RESULTS: Adenosine caused a decrease of APV(Occl) (i.e., coronary steal, in 26 patients [group S], an increase in 19 patients [group R], and no change in 11 patients). The FFR(D) was lower in group S. R(D) and R(C) increased in group S, while R(D) did not change significantly and R(C) decreased in group R. Patients with steal had more severe regional dysfunction. Patients with steal but without an FFR(D) <0.8 tended to have an impaired microvascular function. CONCLUSIONS: We could demonstrate that coronary steal in man is mainly due to a hemodynamically significant donor artery lesion, but can also occur due to an impaired vasodilatory reserve of the microcirculation in the absence of a donor artery lesion. Coronary steal may have an adverse influence on the preservation of myocardial function by collaterals.

Evaluation of the haemodynamic characteristics of drug-eluting stents at implantation and at follow-up.

AIMS: The aim of this study was to investigate the physiologic parameters: fractional flow reserve (FFR), hyperaemic trans-stent gradient (HTG), and wall shear stress (WSS) at implantation and at 6-month follow-up in the drug-eluting sirolimus stent and in its bare metal counterpart implanted in pairs within the same patient. METHODS AND RESULTS: Twenty patients, accepted for percutaneous coronary intervention of at least two coronary arteries with comparable vessel and stenosis characteristics, received at random one sirolimus-eluting stent and one bare metal stent (BMS). Coronary pressure, FFR, HTG, and WSS were measured just after stent implantation and at 6-month follow-up. At 6-month follow-up, FFR was significantly higher in the sirolimus group compared with the bare metal group (0.91+/-0.05 vs. 0.83+/-0.10, P=0.027) and HTG was significantly lower (1.2+/-1.2 vs. 7.5+/-8.1 mmHg, P<0.001). In-stent WSS at 6 months remained normal in the sirolimus group but was elevated in the bare metal group (1.6+/-0.7 vs 3.9+/-3.1 Pa, respectively, P=0.003). CONCLUSION: The physiologic characteristics of the drug-eluting sirolimus stents were superior to those of the equivalent BMS. Six months after implantation, FFR was significantly higher, HTG was significantly lower in arteries treated by a sirolimus stent, and normal WSS was maintained within the drug-eluting stent.

Correlation of echo-Doppler optimization of atrioventricular delay in cardiac resynchronization therapy with invasive hemodynamics in patients with heart failure secondary to ischemic or idiopathic dilated cardiomyopathy.

This study investigated the optimal echocardiographic indexes to determine the most hemodynamically appropriate atrioventricular (AV) delay in cardiac resynchronization therapy (CRT) for heart failure. Doppler echocardiographic optimization of AV delay in CRT has not been correlated with invasive hemodynamic indexes. In 30 patients who underwent CRT, invasive left ventricular (LV) pressure measurements with a sensor-tipped pressure guidewire and Doppler echocardiographic examination were performed <24 hours after pacemaker implantation. Invasively, the optimal sensed AV delay was determined by LV dP/dt(max). The Doppler echocardiographic methods evaluated were the velocity-time integral (VTI) of the transmitral flow (EA VTI), diastolic filling time (EA duration), the VTI of the LV outflow tract or aorta (LV VTI), and Ritter's formula. Biventricular pacing with optimized interventricular and AV delay increased LV dP/dt(max) from 777 +/- 149 to 1,010 +/- 163 dynes/s (p<0.0001). The optimal AV delay with the EA VTI method was concordant with LV dP/dt(max) in 29 of 30 patients (r = 0.96), with EA duration in 20 of 30 patients (r= 0.83), with LV VTI in 13 patients (r = 0.54), and with Ritter's formula in none of the patients (r = 0.35). In conclusion, to obtain the optimal acute hemodynamic benefit of CRT, Doppler echocardiography is a reliable tool to optimize the AV delay compared with the invasive LV dP/dt(max). The measurement of the maximal VTI of mitral inflow is the most accurate method.

Effect of phentolamine on the hyperemic response to adenosine in patients with microvascular disease.

For accurate measurement of the fractional flow reserve (FFR) of the myocardium, the presence of maximum hyperemia is of paramount importance. It has been suggested that the hyperemic effect of the conventionally used hyperemic stimulus, adenosine, could be submaximal in patients who have microvascular dysfunction and that adding alpha-blocking agents could augment the hyperemic response in these patients. We studied the effect of the nonselective alpha-blocking agent phentolamine, which was administered in addition to adenosine after achieving hyperemia, in patients who had microvascular disease and those who did not. Thirty patients who were referred for percutaneous coronary intervention were selected. Of these 30 patients, 15 had strong indications for microvascular disease and 15 did not. FFR was measured using intracoronary adenosine, intravenous adenosine, and intracoronary papaverine before and after intracoronary administration of the nonselective alpha blocker phentolamine. In patients who did not have microvascular disease, no differences in hyperemic response to adenosine were noted, whether or not alpha blockade was given before adenosine administration; FFR levels before and after phentolamine were 0.76 and 0.75, respectively, using intracoronary adenosine (p = 0.10) and 0.75 and 0.74, respectively, using intravenous adenosine (p = 0.20). In contrast, in patients who had microvascular disease, some increase in hyperemic response was observed after administration of phentolamine; FFR levels decreased from 0.74 to 0.70 using intracoronary adenosine (p = 0.003) and from 0.75 to 0.72 using intravenous adenosine (p = 0.04). Although statistically significant, the observed further decrease in microvascular resistance after addition of phentolamine was small and did not affect clinical decision making in any patient. In conclusion, when measuring FFR, routinely adding an alpha-blocking agent to adenosine does not affect clinical decision making.

Alpha-adrenergic receptor blockade and hyperaemic response in patients with intermediate coronary stenoses.

BACKGROUND: Maximal hyperaemia is paramount in the diagnosis of patients with coronary artery disease. However in these patients, enhanced alpha-adrenergic microvascular vasoconstriction may preclude adenosine to induce maximal hyperaemia. AIM: To assess the presence and the clinical relevance of residual microvascular resistance after administration of adenosine. METHODS AND RESULTS: Fractional flow reserve (FFR, calculated by coronary pressure measurements during adenosine-induced hyperaemia) was assessed in 85 patients with an intermediate coronary stenosis (mean diameter stenosis of 50+/-1%) and normal left ventricular function which were divided into the following three groups: (a) 33 patients before and after IC bolus of phentolamine, an alpha1-, alpha2-adrenergic blocker; (b) 32 patients before and after IC bolus of urapidil, a selective alpha1-adrenergic blocker; (c) 20 patients before and after IC bolus of saline. Since minimal luminal diameter remained unchanged before and after phentolamine (1.46+/-0.06 vs. 1.47+/-0.06 mm, ns), urapidil (1.46+/-0.06 vs. 1.39+/-0.08, ns), and saline (1.56+/-0.08 vs. 1.55+/-0.08, ns), changes in FFR reflects changes in microvascular resistance. Overall, phentolamine and urapidil induced a slight but significant decrease in FFR (phentolamine: 0.79+/-0.02 vs. 0.77+/-0.02, p<0.05; urapidil: 0.78+/-0.02 vs. 0.75+/-0.02, p<0.05). However, only 6 patients showed a change in FFR from > or = 0.75 to <0.75 and no patients showed a change in FFR from > or = 0.80 to <0.75 that could have influenced clinical decision making. Saline did not induce any change in FFR. Phentolamine and urapidil induced only transient and negligible haemodynamic changes in heart rate and blood pressure. CONCLUSIONS: The administration of alpha-adrenergic blockers in addition to adenosine unmasks a small, yet clinically irrelevant, degree of residual microvascular tone. The consequential changes in FFR values do not significantly affect clinical decision making.

Epicardial stenosis severity does not affect minimal microcirculatory resistance.

BACKGROUND: Whether minimal microvascular resistance of the myocardium is affected by the presence of an epicardial stenosis is controversial. Recently, an index of microcirculatory resistance (IMR) was developed that is based on combined measurements of distal coronary pressure and thermodilution-derived mean transit time. In normal coronary arteries, IMR correlates well with true microvascular resistance. However, to be applicable in the case of an epicardial stenosis, IMR should account for collateral flow. We investigated the feasibility of determining IMR in humans and tested the hypothesis that microvascular resistance is independent of epicardial stenosis. METHODS AND RESULTS: Thirty patients scheduled for percutaneous coronary intervention were studied. The stenosis was stented with a pressure guidewire, and coronary wedge pressure (P(w)) was measured during balloon occlusion. After successful stenting, a short compliant balloon with a diameter 1.0 mm smaller than the stent was placed in the stented segment and inflated with increasing pressures, creating a 10%, 50%, and 75% area stenosis. At each of the 3 degrees of stenosis, fractional flow reserve (FFR) and IMR were measured at steady-state maximum hyperemia induced by intravenous adenosine. A total of 90 measurements were performed in 30 patients. When uncorrected for P(w), an apparent increase in microvascular resistance was observed with increasing stenosis severity (IMR=24, 27, and 37 U for the 3 different degrees of stenosis; P<0.001). In contrast, when P(w) is appropriately accounted for, microvascular resistance did not change with stenosis severity (IMR=22, 23, and 23 U, respectively; P=0.28). CONCLUSIONS: Minimal microvascular resistance does not change with epicardial stenosis severity, and IMR is a specific index of microvascular resistance when collateral flow is properly taken into account.

Percutaneous coronary intervention or bypass surgery in multivessel disease? A tailored approach based on coronary pressure measurement.

The optimal revascularization strategy, percutaneous coronary intervention (PCI) or coronary artery bypass graft surgery (CABG), for patients with multivessel coronary artery disease (MVD) remains controversial. The aim of the present study was to compare the long-term outcomes after selective PCI of only hemodynamically significant lesions (fractional flow reserve, or FFR < 0.75) to CABG of all stenoses in patients with MVD. In 150 patients with MVD referred for CABG, FFR was determined in 381 coronary arteries considered for bypass grafting. If the FFR was less than 0.75 in three vessels or in two vessels including the proximal left anterior descending (LAD) artery, CABG was performed (CABG group). If only one or two vessels were physiologically significant (not including the proximal LAD), PCI of those lesions was performed (PCI group). Of the 150 patients, 87 fulfilled the criteria for CABG and 63 for PCI. There were no significant differences in the angiographic or other baseline characteristics between the two groups. At 2-year follow-up, no differences were seen in adverse events, including repeat revascularization (event-free survival 74% in the CABG group and 72% in the PCI group). A similar number of patients were free from angina (84% in the CABG group and 82% in the PCI group). Importantly, the results in both groups were as good as the surgical groups in previous studies comparing PCI and CABG in MVD. In patients with multivessel disease, PCI in those with one or two hemodynamically significant lesions as identified by an FFR < 0.75 yields a similar favorable outcome as CABG in those with three or more culprit lesions despite a similar angiographic extent of disease.

A physiologically representative in vitro model of the coronary circulation.

With the development of clinical diagnostic techniques to investigate the coronary circulation in conscious humans, the in vitro validation of such newly developed techniques is of major importance. The aim of this study was to develop an in vitro model that is able to mimic the coronary circulation in such a way that coronary pressure and flow signals under baseline as well as hyperaemic conditions are approximated as realistically as possible and are in accordance with recently gained insights into such signals in conscious man. In the present in vitro model the heart, the systemic and coronary circulation are modelled on the basis of the elements of a lumped parameter mathematical model only consisting of elements that can be represented by segments in an experimental set-up. A collapsible tube, collapsed by the ventricular pressure, represents the variable resistance and volume behaviour of the endocardial part of the myocardium. The pressure and flow signals obtained are similar to physiological human coronary pressure and flow, both for baseline and hyperaemic conditions. The model allows for in vitro evaluation of clinical diagnostic techniques.

Microvascular resistance is not influenced by epicardial coronary artery stenosis severity: experimental validation.

BACKGROUND: The effect of epicardial artery stenosis on myocardial microvascular resistance remains controversial. Recruitable collateral flow, which may affect resistance, was not incorporated into previous measurements. METHODS AND RESULTS: In an open-chest pig model, distal coronary pressure was measured with a pressure wire, and the apparent minimal microvascular resistance was calculated during peak hyperemia as pressure divided by flow, measured either with a flow probe around the coronary artery (R(micro app)) or with a novel thermodilution technique (apparent index of microcirculatory resistance [IMR(app)]). These apparent resistances were compared with the actual R(micro) and IMR after the coronary wedge pressure and collateral flow were incorporated into the calculation. Measurements were made at baseline (no stenosis) and after creation of moderate and severe epicardial artery stenoses. In 6 pigs, 189 measurements of R(micro) and IMR were made under the various epicardial artery conditions. Without consideration of collateral flow, R(micro app) (0.43+/-0.12 to 0.46+/-0.10 to 0.51+/-0.11 mm Hg/mL per minute) and IMR(app) (14+/-4 to 17+/-7 to 20+/-10 U) increased progressively and significantly with increasing epicardial artery stenosis (P<0.001 for both). With the incorporation of collateral flow, neither R(micro) nor IMR increased as a result of increasing epicardial artery stenosis. CONCLUSIONS: After collateral flow is taken into account, the minimum achievable microvascular resistance is not affected by increasing epicardial artery stenosis.

Myocardial resistance assessed by guidewire-based pressure-temperature measurement: in vitro validation.

By injecting a few cubic centimeters of saline into the coronary artery and using thermodilution principles, mean transit time (T(mn)) of the injectate can be calculated and is inversely proportional to coronary blood flow. Because microvascular resistance equals distal coronary pressure (P(d)) divided by myocardial flow, the product P(d). T(mn) provides an index of myocardial resistance (IMR). In this in vitro study in a physiologic model of the coronary circulation, we compared IMR to true myocardial resistance (TMR) at different degrees of myocardial resistance and at different degrees of epicardial stenosis. Absolute blood flow was varied from 42 to 203 ml/min and TMR varied from 0.39 to 1.63 dynes. sec/cm(5). Inverse mean transit time correlated well to absolute blood flow (R(2) = 0.93). Furthermore, an excellent correlation was found between IMR and TMR (R(2) = 0.94). IMR was independent on the severity of epicardial stenosis and thus specific for myocardial resistance. Thus, using one single guidewire, both fractional flow reserve and IMR can be measured simultaneously as indexes of epicardial and microvascular disease, respectively, enabling separate assessment of both coronary arterial and microvascular disease.