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.

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.

Gottliebson WM, Effat MA. Influence of heart rate on fractional flow reserve, pressure drop coefficient, and lesion flow coefficient for epicardial coronary stenosis in a porcine model. Am J Physiol Heart Circ Physiol 300: H382-H387, 2011. First published October 8, 2010 doi:10.1152/ajpheart.00412.2010.-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 (CDPe, 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 Ͻ 120 and HR Ͼ 120 beats/min, in the presence of epicardial coronary lesions of Ͻ50% AS and Ͼ50% AS. The mean values of FFR, CDPe, and LFC were significantly different (P Ͻ 0.05) for lesions of Ͻ50% AS and Ͼ50% AS (0.88 Ϯ 0.04, 0.76 Ϯ 0.04; 62 Ϯ 30, 151 Ϯ 35, and 0.10 Ϯ 0.02 and 0.16 Ϯ 0.01, respectively). The mean values of FFR and CDPe were not significantly different (P Ͼ 0.05) for variable HR conditions of HR Ͻ 120 and HR Ͼ 120 beats/min (FFR, 0.81 Ϯ 0.04 and 0.82 Ϯ 0.04; and CDPe, 95 Ϯ 33 and 118 Ϯ 36). The mean values of LFC do somewhat vary with HR (0.14 Ϯ 0.01 and 0.12 Ϯ 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. coronary disease; hemodynamics; catheterization CORONARY ANGIOGRAPHY is the current gold standard for detecting epicardial coronary artery disease. Augmenting this anatomical data with coronary functional parameters (pressure, flow, and/or velocity) provides unique information that facilitates fully informed therapeutic decision making in the catheterization laboratory. Several invasive functional approaches have been used for the past several years within the cardiac catheterization laboratory that allow for a determination of the functional significance of epicardial coronary stenoses. These methods include measurement of coronary flow reserve [CFR, the ratio of hyperemic flow to basal flow (10) (9), an advanced func...

BackgroundTransient receptor potential vanilloid 2 is a calcium channel activated by probenecid. Probenecid is a Food and Drug Administration–approved uricosuric drug that has recently been shown to induce positive lusitropic and inotropic effects in animal models through cardiomyocyte transient receptor potential vanilloid 2 activation. The aim of this study was to test the hypothesis that oral probenecid can improve cardiac function and symptomatology in patients with heart failure with reduced ejection fraction and to further elucidate its calcium‐dependent effects on myocyte contractility.Methods and ResultsThe clinical trial recruited stable outpatients with heart failure with reduced ejection fraction randomized in a single‐center, double‐blind, crossover design. Clinical data were collected including a dyspnea assessment, physical examination, ECG, echocardiogram to assess systolic and diastolic function, a 6‐minute walk test, and laboratory studies. In vitro force generation studies were performed on cardiomyocytes isolated from murine tissue exposed to probenecid or control treatments. The clinical trial recruited 20 subjects (mean age 57 years, mean baseline fractional shortening of 13.6±1.0%). Probenecid therapy increased fractional shortening by 2.1±1.0% compared with placebo −1.7±1.0% (P=0.007). Additionally, probenecid improved diastolic function compared with placebo by decreasing the E/E′ by −2.95±1.21 versus 1.32±1.21 in comparison to placebo (P=0.03). In vitro probenecid increased myofilament force generation (92.36 versus 80.82 mN/mm2, P<0.05) and calcium sensitivity (pCa 5.67 versus 5.60, P<0.01) compared with control.ConclusionsProbenecid improves cardiac function with minimal effects on symptomatology and no significant adverse effects after 1 week in patients with heart failure with reduced ejection fraction and increases force development and calcium sensitivity at the cardiomyocyte level.Clinical Trial Registration URL: https://www.clinicaltrials.gov. Unique identifier: NCT01814319.

Background In the absence of obstructive coronary stenoses, abnormality of noninvasive stress tests (NIT) in patients with chronic coronary syndromes may indicate myocardial ischemia of nonobstructive coronary arteries (INOCA). The differential prognosis of INOCA according to the presence of coronary microvascular dysfunction (CMD) and incremental prognostic value of CMD with intracoronary physiologic assessment on top of NIT information remains unknown. Methods and Results From the international multicenter registry of intracoronary physiologic assessment (ILIAS [Inclusive Invasive Physiological Assessment in Angina Syndromes] registry, N=2322), stable patients with NIT and nonobstructive coronary stenoses with fractional flow reserve >0.80 were selected. INOCA was diagnosed when patients showed positive NIT results. CMD was defined as coronary flow reserve ≤2.5. According to the presence of INOCA and CMD, patients were classified into 4 groups: group 1 (no INOCA nor CMD, n=116); group 2 (only CMD, n=90); group 3 (only INOCA, n=41); and group 4 (both INOCA and CMD, n=40). The primary outcome was major adverse cardiovascular events, a composite of all‐cause death, target vessel myocardial infarction, or clinically driven target vessel revascularization at 5 years. Among 287 patients with nonobstructive coronary stenoses (fractional flow reserve=0.91±0.06), 81 patients (38.2%) were diagnosed with INOCA based on positive NIT. By intracoronary physiologic assessment, 130 patients (45.3%) had CMD. Regardless of the presence of INOCA, patients with CMD showed a significantly lower coronary flow reserve and higher hyperemic microvascular resistance compared with patients without CMD ( P <0.001 for all). The cumulative incidence of major adverse cardiovascular events at 5 years were 7.4%, 21.3%, 7.7%, and 34.4% in groups 1 to 4. By documenting CMD (groups 2 and 4), intracoronary physiologic assessment identified patients at a significantly higher risk of major adverse cardiovascular events at 5 years compared with group 1 (group 2: adjusted hazard ratio [HR adjusted ], 2.88; 95% CI, 1.52–7.19; P =0.024; group 4: HR adjusted , 4.00; 95% CI, 1.41–11.35; P =0.009). Conclusions In stable patients with nonobstructive coronary stenoses, a diagnosis of INOCA based only on abnormal NIT did not identify patients with higher risk of long‐term cardiovascular events. Incorporating intracoronary physiologic assessment to NIT information in patients with nonobstructive disease allowed identification of patient subgroups with up to 4‐fold difference in long‐term cardiovascular events. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT04485234.