Mohamed Effat

Safety and efficacy of drug eluting stents compared with bare metal stents for saphenous vein graft interventions: A comprehensive meta-analysis of randomized trials and observational studies comprising 7,994 patients†

Background: Saphenous vein graft (SVG) lesions remain amongst the most challenging lesions for percutaneous coronary intervention (PCI). It is unknown whether drug eluting stents (DES) are superior to bare metal stents (BMS) for such lesions. Our objective is to determine the safety and efficacy of DES compared with BMS for SVG lesions by performing a meta‐analysis of clinical trials and observational studies. Data Sources: PubMed, Cochrane Register of Controlled Trials, conference proceedings, and internet‐based resources of clinical trials. Study Selection:Studies comparing DES vs. BMS for SVG lesions with at least > 30 patients in each study reporting the outcomes of interest [death, myocardial infarction (MI), target vessel revascularization (TVR), stent thrombosis (ST), and the composite of death, TVR and MI (major adverse cardiac events; MACE)] with at least 6 months clinical follow‐up. The primary outcome of interest was death. Results:Two randomized trials, one subgroup analysis of a randomized trial and 26 observational studies comprising a total of 7,994 patients (4,187 patients in DES and 3,807 patients in BMS group) were included in the analysis .Mean follow‐up duration was 21 ± 11 months (6–48 months). In the overall population, MACE events were 19% in DES and 28% in BMS with a risk ratio (RR) of 0.7 (0.6, 0.8) P < 0.00001. This effect of MACE was sustained in studies with >2 years follow‐up with RR of 0.77 (0.65, 0.91) P = 0.003. Death rate was 7.8% in DES and 9% in BMS with a RR of 0.82 (0.7, 0.97) P = 0.02. MI rate was 5.7% in DES and 7.6% in BMS with RR of 0.72 (0.57, 0.91) P = 0.007. TVR was 12% in DES and 17% in BMS with RR of 0.71 (0.59, 0.85) P = 0.0002. ST was 1% in DES and 1.7 % in BMS RR of 0.61 (0.35, 1.06) P = 0.08. Specifically in randomized controlled trials, DES were associated with no significant differences in overall mortality [RR = 1.97; 95% confidence interval (CI), 0.17–23; P = 0.58] or MI (RR = 1.24; 95% CI, 0.3–5.5; P = 0.78) compared with BMS. Conclusions:Based on the results of this meta‐analysis, DES may be considered as a safe and efficacious option for the percutaneous intervention of SVG lesions.

Hemodynamic diagnostics of epicardial coronary stenoses: in-vitro experimental and computational study

BackgroundThe severity of epicardial coronary stenosis can be assessed by invasive measurements of trans-stenotic pressure drop and flow. A pressure or flow sensor-tipped guidewire inserted across the coronary stenosis causes an overestimation in true trans-stenotic pressure drop and reduction in coronary flow. This may mask the true severity of coronary stenosis. In order to unmask the true severity of epicardial stenosis, we evaluate a diagnostic parameter, which is obtained from fundamental fluid dynamics principles. This experimental and numerical study focuses on the characterization of the diagnostic parameter, pressure drop coefficient, and also evaluates the pressure recovery downstream of stenoses.MethodsThree models of coronary stenosis namely, moderate, intermediate and severe stenosis, were manufactured and tested in the in-vitro set-up simulating the epicardial coronary network. The trans-stenotic pressure drop and flow distal to stenosis models were measured by non-invasive method, using external pressure and flow sensors, and by invasive method, following guidewire insertion across the stenosis. The viscous and momentum-change components of the pressure drop for various flow rates were evaluated from quadratic relation between pressure drop and flow. Finally, the pressure drop coefficient (CDPe) was calculated as the ratio of pressure drop and distal dynamic pressure. The pressure recovery factor (η) was calculated as the ratio of pressure recovery coefficient and the area blockage.ResultsThe mean pressure drop-flow characteristics before and during guidewire insertion indicated that increasing stenosis causes a shift in dominance from viscous pressure to momentum forces. However, for intermediate (~80%) area stenosis, which is between moderate (~65%) and severe (~90%) area stenoses, both losses were similar in magnitude. Therefore, guidewire insertion plays a critical role in evaluating the hemodynamic severity of coronary stenosis. More importantly, mean CDPe increased (17 ± 3.3 to 287 ± 52, n = 3, p < 0.01) and mean η decreased (0.54 ± 0.04 to 0.37 ± 0.05, p < 0.01) from moderate to severe stenosis during guidewire insertion.ConclusionThe wide range of CDPe is not affected that much by the presence of guidewire. CDPe can be used in clinical practice to evaluate the true severity of coronary stenosis due to its significant difference between values measured at moderate and severe stenoses.

Impact of kissing balloon inflation on the main vessel stent volume, area, and symmetry after side-branch dilation in patients with coronary bifurcation lesions: a serial volumetric intravascular ultrasound study.

OBJECTIVES Intravascular ultrasound (IVUS) was performed to investigate the impact of kissing balloon inflation (KBI) on the main vessel (MV) stent volume, area, and symmetry after side-branch (SB) dilation in patients with coronary bifurcation lesions (CBL). BACKGROUND It remains controversial whether KBI would restore the MV stent area and symmetry loss after SB dilation. METHODS A total of 88 serial IVUS examinations of the MV were performed after MV angioplasty, MV stenting, SB dilation, and KBI in 22 patients with CBL. The MV stent was divided into proximal, bifurcation, and distal segments; the stent volume index (SVI), minimal stent area (MSA), stent symmetry index (SSI), and external elastic membrane (EEM) volume index were measured in 198 stent segments and compared after MV stenting, SB dilation, and KBI. RESULTS In the bifurcation segment, SVI, MSA, and SSI were significantly smaller after SB dilation than after MV stenting and KBI (SVI was 6.10 ± 1.50 mm(3)/mm vs. 6.68 ± 1.60 mm(3)/mm and 6.57 ± 1.60 mm(3)/mm, respectively, p < 0.05; MSA was 5.15 ± 1.30 mm(2) vs. 6.08 ± 1.40 mm(2) and 5.86 ± 1.50 mm(2), respectively, p < 0.05; and SSI was 0.78 ± 0.02 mm(2) vs. 0.87 ± 0.03 mm(2) and 0.84 ± 0.03 mm(2), respectively, p < 0.05). KBI restored the MV SVI, MSA, and SSI after SB dilation. In the proximal segment, SVI, MSA, and EEM volume index were significantly larger, but SSI was smaller after KBI than after MV stenting and SB dilation. In the distal segment, neither SB dilation nor KBI had a significant impact on the MV stent volume or symmetry. CONCLUSIONS This is the first comprehensive volumetric IVUS analysis of CBL, to our knowledge, demonstrating that KBI restores the MV stent volume, area, and symmetry loss after SB dilation in the bifurcation segment, and induces asymmetric stent expansion in the proximal segment.

Influence of heart rate on fractional flow reserve, pressure drop coefficient, and lesion flow coefficient for epicardial coronary stenosis in a porcine model

A limitation in the use of invasive coronary diagnostic indexes is that fluctuations in hemodynamic factors such as heart rate (HR), blood pressure, and contractility may alter resting or hyperemic flow measurements and may introduce uncertainties in the interpretation of these indexes. In this study, we focused on the effect of fluctuations in HR and area stenosis (AS) on diagnostic indexes. We hypothesized that the pressure drop coefficient (CDP(e), ratio of transstenotic pressure drop and distal dynamic pressure), lesion flow coefficient (LFC, square root of ratio of limiting value CDP and CDP at site of stenosis) derived from fluid dynamics principles, and fractional flow reserve (FFR, ratio of average distal and proximal pressures) are independent of HR and can significantly differentiate between the severity of stenosis. Cardiac catheterization was performed on 11 Yorkshire pigs. Simultaneous measurements of distal coronary arterial pressure and flow were performed using a dual sensor-tipped guidewire for HR < 120 and HR > 120 beats/min, in the presence of epicardial coronary lesions of <50% AS and >50% AS. The mean values of FFR, CDP(e), and LFC were significantly different (P < 0.05) for lesions of <50% AS and >50% AS (0.88 ± 0.04, 0.76 ± 0.04; 62 ± 30, 151 ± 35, and 0.10 ± 0.02 and 0.16 ± 0.01, respectively). The mean values of FFR and CDP(e) were not significantly different (P > 0.05) for variable HR conditions of HR < 120 and HR > 120 beats/min (FFR, 0.81 ± 0.04 and 0.82 ± 0.04; and CDP(e), 95 ± 33 and 118 ± 36). The mean values of LFC do somewhat vary with HR (0.14 ± 0.01 and 0.12 ± 0.02). In conclusion, fluctuations in HR have no significant influence on the measured values of CDP(e) and FFR but have a marginal influence on the measured values of LFC. However, all three parameters can significantly differentiate between stenosis severities. These results suggest that the diagnostic parameters can be potentially used in a better assessment of coronary stenosis severity under a clinical setting.

Functional diagnosis of coronary stenoses using pressure drop coefficient: a pilot study in humans.

Myocardial fractional flow reserve (FFR) in conjunction with coronary flow reserve (CFR) is used to evaluate the hemodynamic severity of coronary lesions. However, discordant results between FFR and CFR have been observed in intermediate coronary lesions. A functional parameter, pressure drop coefficient (CDP; ratio of pressure drop to distal dynamic pressure), was assessed using intracoronary pressure drop (dp) and average peak velocity (APV). The CDP is a nondimensional ratio, derived from fundamental fluid dynamic principles. We sought to evaluate the correlation of CDP with FFR, CFR, and hyperemic stenosis resistance (HSR: ratio of pressure drop to APV) in human subjects.

Effect of heart rate on hemodynamic endpoints under concomitant microvascular disease in a porcine model

Diagnosis of the ischemic power of epicardial stenosis with concomitant microvascular disease (MVD) is challenging during coronary interventions, especially under variable hemodynamic factors like heart rate (HR). The goal of this study is to assess the influence of variable HR and percent area stenosis (%AS) in the presence of MVD on pressure drop coefficient (CDP; ratio of transstenotic pressure drop to the distal dynamic pressure) and lesion flow coefficient (LFC; ratio of %AS to the CDP at the throat region). We hypothesize that CDP and LFC are independent of HR. %AS and MVD were created using angioplasty balloons and 90-μm microspheres, respectively. Simultaneous measurements of pressure drop (DP) and velocity were done in 11 Yorkshire pigs. Fractional flow reserve (FFR), CDP, and LFC were calculated for the groups HR < 120 and HR > 120 beats/min, %AS < 50 and %AS > 50, and additionally for DP < 14 and DP > 14 mmHg, and analyzed using regression and ANOVA analysis. Regression analysis showed independence between HR and the FFR, CDP, and LFC while it showed dependence between %AS and the FFR, CDP, and LFC. In the ANOVA analysis, for the HR < 120 beats/min and HR > 120 beats/min groups, the values of FFR (0.82 ± 0.02 and 0.82 ± 0.02), CDP (83.15 ± 26.19 and 98.62 ± 26.04), and LFC (0.16 ± 0.03 and 0.15 ± 0.03) were not significantly different (P > 0.05). However, for %AS < 50 and %AS > 50, the FFR (0.89 ± 0.02 and 0.75 ± 0.02), CDP (35.97 ± 25.79.10 and 143.80 ± 25.41), and LFC (0.09 ± 0.03 and 0.22 ± 0.03) were significantly different (P < 0.05). A similar trend was observed between the DP groups. Under MVD conditions, FFR, CDP, and LFC were not significantly influenced by changes in HR, while they can significantly distinguish %AS and DP groups.

Effect of myocardial contractility on hemodynamic end points under concomitant microvascular disease in a porcine model

In this study, coronary diagnostic parameters, pressure drop coefficient (CDP: ratio of trans-stenotic pressure drop to distal dynamic pressure), and lesion flow coefficient (LFC: ratio of % area stenosis (%AS) to the CDP at throat region), were evaluated to distinguish levels of %AS under varying contractility conditions, in the presence of microvascular disease (MVD). In 10 pigs, %AS and MVD were created using angioplasty balloons and 90-μm microspheres, respectively. Simultaneous measurements of pressure drop, left ventricular pressure (p), and velocity were obtained. Contractility was calculated as (dp/dt)max, categorized into low contractility <900 mmHg/s and high contractility >900 mmHg/s, and in each group, compared between %AS <50 and >50 using analysis of variance. In the presence of MVD, between the %AS <50 and >50 groups, values of CDP (71 ± 1.4 and 121 ± 1.3) and LFC (0.10 ± 0.04 and 0.19 ± 0.04) were significantly different (P < 0.05), under low-contractility conditions. A similar %AS trend was observed under high-contractility conditions (CDP: 18 ± 1.4 and 91 ± 1.4; LFC: 0.08 ± 0.04 and 0.25 ± 0.04). Under MVD conditions, similar to fractional flow reserve, CDP and LFC were not influenced by contractility.

The Role of Vascular Imaging in Guiding Routine Percutaneous Coronary Interventions: A Meta‐Analysis of Bare Metal Stent and Drug‐Eluting Stent Trials

BACKGROUND The routine use of vascular imaging including intravascular ultrasound (IVUS) and optical coherence tomography (OCT) in guiding percutaneous coronary interventions (PCI) is still controversial especially when using drug-eluting stents. A meta-analysis of trials using bare metal stents was previously published. METHODS We conducted a meta-analysis of available published trials that compared imaging-guided PCI and angiography-guided PCI in patients undergoing routine PCI only. Trials that enrolled patients with acute coronary syndrome were excluded to decrease heterogeneity. We aimed to study both drug-eluting stents (DES) as well as bare metal stents (BMS). We identified seven randomized controlled trials on IVUS-guided bare metal stents. We also identified three randomized controlled trials on IVUS-guided drug-eluting stents. To improve the power of the drug-eluting stent data, we identified, and included, nine registries that compared IVUS-guided PCI to angiography-guided PCI in the drug-eluting stent era. Nonrandomized registries that included BMS only were excluded as there are multiple previous meta-analyses that studied these patients. Finally, we identified one registry that compared OCT-guided PCI to angiography-guided PCI using either a BMS or a DES. A total of 14,197 patients were studied overall. The meta-analysis was conducted using a random effect model. RESULTS Imaging guidance was associated with a significantly larger postintervention minimal luminal diameter (SMD: 0.289. 95% CI: 0.213-0.365. P < 0.01). Imaging-guided stenting was associated with a significant decrease in the major adverse cardiac events (MACE) in the DES patients (odds ratio: 0.810. 95% CI: 0.719-0.912. P < 0.01) and combined DES and BMS patients (odds ratio: 0.782. 95% CI: 0.686-0.890. P < 0.01). Imaging guidance was associated with significantly lower events of death from all causes in DES patients (odds ratio: 0.654. 95% CI: 0.468-0.916. P < 0.01) and in the combined DES and BMS patients (odds ratio: 0.727. 95% CI: 0.540-0.980. P < 0.01). The risk of myocardial infarction (MI) was significantly lower with imaging guidance in both, DES patients (odds ratio: 0.551. 95% CI: 0.363-0.837. P < 0.01) and combined DES and BMS patients (odds ratio: 0.589. 95% CI: 0.425-0.816. P < 0.01). This may, in part, be explained by the significantly lower risk of stent thrombosis in imaging-guided DES patients (odds ratio: 0.651. 95% CI: 0.499-0.850. P < 0.01) and combined DES and BMS patients (odds ratio: 0.665. 95% CI: 0.513-0.862. P < 0.01). Patients who received a DES showed no difference between imaging guidance and angiography guidance in repeated target lesion revascularization, while the analysis of BMS alone and the DES and BMS combined showed significant superiority of the imaging-guided PCI group. CONCLUSION Imaging-guided PCI significantly lowered the risk of death, MI, stent thrombosis, and the combined MACE in DES-implanted patients and all stented patients (DES or BMS). However, imaging guidance had no significant effect on repeated target vessel or target lesion revascularization in patients who received DES, likely due to the effect of the drug in the stent.

Diagnostic cutoff for pressure drop coefficient in relation to fractional flow reserve and coronary flow reserve: A patient-level analysis

Functional assessment of intermediate coronary stenosis during cardiac catheterization is conducted using diagnostic parameters like fractional flow reserve (FFR), coronary flow reserve (CFR), hyperemic stenosis resistance index (HSR), and hyperemic microvascular resistance (HMR). CDP (ratio of pressure drop across a stenosis to distal dynamic pressure), a nondimensional index derived from fundamental fluid dynamic principles, based on a combination of intracoronary pressure, and flow measurements may improve the functional assessment of coronary lesion severity.

Pathophysiology of ischemic heart disease: an overview.

Ischemia refers to inadequate supply of oxygen and metabolic substrate to an organ. The term myocardial ischemia covers a heterogeneous group of clinical syndromes, globally called ischemic heart disease, which includes chronic stable angina at one end of the spectrum and acute myocardial infarction at the other end. Between these two extremes, there is a broad myriad of intermediate syndromes, all having in common a mismatch between oxygen demand and supply. Ischemic heart disease is the leading cause of all morbidity and mortality in the United States. It is reasonable to assume that proper intervention and follow-up care based on knowledge of pathophysiology is imperative to the professional nursing care of patients with this disease. In this article, the author presents a brief survey of the current state of the discussion from a pathophysiologic viewpoint that highlights the dynamic nature of the disease and its related clinical implications.