In the first part of this study, we identified the existence of a diastolic interval in which intracoronary resistance at rest is equivalent to time-averaged resistance during FFR measurements. We hypothesize that pressure measurements obtained selectively at this specific interval of the cardiac cycle would allow a new pressure-derived index of stenosis severity that does not require pharmacologic vasodilation; we term this the instantaneous wave-free ratio (iFR). In the second part of the study, this hypothesis was tested in a larger population by comparing iFR and FFR measurements.
Assessment of Intermediate Coronary Artery Lesion with Fractional Flow Reserv...Premier Publishers
Fraction flow reserve (FFR) is considered the gold standard for assessing intermediate coronary lesions. Retrospective data analyses showed variable relationship between intravascular ultrasound (IVUS) parameters and FFR results. This study aimed to determine the optimal minimum lumen area (MLA) by IVUS that correlates with FFR and to assess the correlation between two modalities in assessing intermediate coronary lesions. Methods: Fifty eight intermediate coronary lesions mainly located in proximal and mid segments of large main coronary vessels with RVD (3-4mm) were analyzed using both IVUS and FFR to assess the significance of coronary stenting and to determine the optimal IVUS-MLA that correlates with FFR value < 0.8. Results: IVUS-MLA ranged from 2.5 to 4.2 mm2 had a highly significant positive correlation with FFR value < 0.8 (p < 0.0001). Using the ROC curve analysis, IVUS-MLA < 3.9 mm2 (84.2% sensitivity, 80% specificity, area under curve (AUC) = 0.68) was the best threshold value for identifying FFR <0.8>< 0.8 in coronary vessels with RVD (3-4mm). Different MLA cutoffs should be used for different vessel diameters.
This document discusses fractional flow reserve (FFR) guided coronary interventions. It begins by outlining challenges in daily practice when treating patients with recent myocardial infarction or stable angina. It then defines FFR as a ratio used to assess the physiologic consequences of coronary obstructions. Values less than 0.75 are considered functionally ischemic. The document discusses applications of FFR for single-vessel disease, left main stenosis, tandem lesions, and multi-vessel coronary artery disease. It also compares FFR to intravascular ultrasound and discusses the DEFER study and FAME 2 study which evaluated outcomes of FFR-guided versus angiography-guided interventions.
http://www.theheart.org/web_slides/1416535.do
A trial to compare Fractional Flow Reserve versus Angiography for Guiding PCI in Patients with Multivessel Coronary Artery Disease II
This document discusses the assessment of intracardiac shunts by cardiac catheterization. It describes how an oximetry run is performed to detect a left-to-right shunt by measuring oxygen saturation at various locations in the heart and great vessels. A significant step-up in oxygen saturation between the right atrium and ventricle or pulmonary artery suggests a left-to-right shunt. The document also discusses calculating shunt ratios using indicator dilution techniques and identifying shunt locations with angiography and pressure measurements. Complications of the procedure are outlined.
This article reviews the role of invasive hemodynamics in the care of patients across the
entire spectrum of human heart failure.
Conceptual principles of ventricular function, ventricular-arterial interaction, load
response, and ventricular interaction in the right and left heart are reviewed.
Principles and practice of invasive exercise testing are provided, along with detailed
discussions on the role of invasive hemodynamics in the evaluation and management of
advanced heart failure, shock, mechanical circulatory support, and pulmonary
hypertension.
1) The document discusses whether fractional flow reserve (FFR) guided interventions should be routine or individualized for patients with multivessel coronary artery disease (MVD).
2) It summarizes the findings of the FAME study which found that an FFR-guided approach reduced major adverse cardiac events compared to an angiography-guided approach alone.
3) The document concludes that while FFR provides useful functional information, an individualized approach is needed considering factors like the number of diseased vessels and whether the study directly compared outcomes to CABG.
Year in cardiology imaging 2019 - echocardiographyPraveen Nagula
This document summarizes findings from studies on cardiac imaging techniques. Key points include:
1) A study of over 1,000 individuals found that E/e'sr, a measure of left ventricular filling pressures using speckle tracking echocardiography, was a stronger predictor of cardiovascular death and events than E/E' and provided incremental value over current risk models.
2) Increased left ventricular mechanical dispersion, a measure of contraction heterogeneity, was associated with higher risk of cardiovascular death in a large population even after adjusting for factors.
3) Studies found a U-shaped relationship between left ventricular ejection fraction and mortality, with a nadir at 60-65%, indicating risks with both higher and lower
This document discusses various echocardiographic scoring systems used to assess mitral valve anatomy and predict outcomes of percutaneous balloon mitral valvuloplasty (PBMV). The Wilkins score and Commissural Calcification score are described in detail. The Wilkins score grades leaflet thickening, mobility, calcification and subvalvular involvement on a scale of 4-16. A score ≤8 indicates favorable anatomy for PBMV. The Commissural Calcification score quantifies calcification at each commissure. Other discussed scores include the Cormier score, RT-3DE score, Chen score, Reid score and Nobuyoshi score. Limitations of the scoring systems and ideas for an ideal future scoring
Assessment of Intermediate Coronary Artery Lesion with Fractional Flow Reserv...Premier Publishers
Fraction flow reserve (FFR) is considered the gold standard for assessing intermediate coronary lesions. Retrospective data analyses showed variable relationship between intravascular ultrasound (IVUS) parameters and FFR results. This study aimed to determine the optimal minimum lumen area (MLA) by IVUS that correlates with FFR and to assess the correlation between two modalities in assessing intermediate coronary lesions. Methods: Fifty eight intermediate coronary lesions mainly located in proximal and mid segments of large main coronary vessels with RVD (3-4mm) were analyzed using both IVUS and FFR to assess the significance of coronary stenting and to determine the optimal IVUS-MLA that correlates with FFR value < 0.8. Results: IVUS-MLA ranged from 2.5 to 4.2 mm2 had a highly significant positive correlation with FFR value < 0.8 (p < 0.0001). Using the ROC curve analysis, IVUS-MLA < 3.9 mm2 (84.2% sensitivity, 80% specificity, area under curve (AUC) = 0.68) was the best threshold value for identifying FFR <0.8>< 0.8 in coronary vessels with RVD (3-4mm). Different MLA cutoffs should be used for different vessel diameters.
This document discusses fractional flow reserve (FFR) guided coronary interventions. It begins by outlining challenges in daily practice when treating patients with recent myocardial infarction or stable angina. It then defines FFR as a ratio used to assess the physiologic consequences of coronary obstructions. Values less than 0.75 are considered functionally ischemic. The document discusses applications of FFR for single-vessel disease, left main stenosis, tandem lesions, and multi-vessel coronary artery disease. It also compares FFR to intravascular ultrasound and discusses the DEFER study and FAME 2 study which evaluated outcomes of FFR-guided versus angiography-guided interventions.
http://www.theheart.org/web_slides/1416535.do
A trial to compare Fractional Flow Reserve versus Angiography for Guiding PCI in Patients with Multivessel Coronary Artery Disease II
This document discusses the assessment of intracardiac shunts by cardiac catheterization. It describes how an oximetry run is performed to detect a left-to-right shunt by measuring oxygen saturation at various locations in the heart and great vessels. A significant step-up in oxygen saturation between the right atrium and ventricle or pulmonary artery suggests a left-to-right shunt. The document also discusses calculating shunt ratios using indicator dilution techniques and identifying shunt locations with angiography and pressure measurements. Complications of the procedure are outlined.
This article reviews the role of invasive hemodynamics in the care of patients across the
entire spectrum of human heart failure.
Conceptual principles of ventricular function, ventricular-arterial interaction, load
response, and ventricular interaction in the right and left heart are reviewed.
Principles and practice of invasive exercise testing are provided, along with detailed
discussions on the role of invasive hemodynamics in the evaluation and management of
advanced heart failure, shock, mechanical circulatory support, and pulmonary
hypertension.
1) The document discusses whether fractional flow reserve (FFR) guided interventions should be routine or individualized for patients with multivessel coronary artery disease (MVD).
2) It summarizes the findings of the FAME study which found that an FFR-guided approach reduced major adverse cardiac events compared to an angiography-guided approach alone.
3) The document concludes that while FFR provides useful functional information, an individualized approach is needed considering factors like the number of diseased vessels and whether the study directly compared outcomes to CABG.
Year in cardiology imaging 2019 - echocardiographyPraveen Nagula
This document summarizes findings from studies on cardiac imaging techniques. Key points include:
1) A study of over 1,000 individuals found that E/e'sr, a measure of left ventricular filling pressures using speckle tracking echocardiography, was a stronger predictor of cardiovascular death and events than E/E' and provided incremental value over current risk models.
2) Increased left ventricular mechanical dispersion, a measure of contraction heterogeneity, was associated with higher risk of cardiovascular death in a large population even after adjusting for factors.
3) Studies found a U-shaped relationship between left ventricular ejection fraction and mortality, with a nadir at 60-65%, indicating risks with both higher and lower
This document discusses various echocardiographic scoring systems used to assess mitral valve anatomy and predict outcomes of percutaneous balloon mitral valvuloplasty (PBMV). The Wilkins score and Commissural Calcification score are described in detail. The Wilkins score grades leaflet thickening, mobility, calcification and subvalvular involvement on a scale of 4-16. A score ≤8 indicates favorable anatomy for PBMV. The Commissural Calcification score quantifies calcification at each commissure. Other discussed scores include the Cormier score, RT-3DE score, Chen score, Reid score and Nobuyoshi score. Limitations of the scoring systems and ideas for an ideal future scoring
Revascularization in heart faliure seminarAnkit Jain
This document discusses revascularization in patients with heart failure due to coronary artery disease and residual left ventricular dysfunction. It provides details on myocardial hibernation and stunning - two states of sustained contractile dysfunction despite viable myocardium. Revascularization can lead to improved survival and reverse remodeling in such patients if a sufficient amount of viable myocardium is present. Techniques to assess myocardial viability include stress echocardiography, nuclear imaging with SPECT or PET, and cardiac magnetic resonance. Revascularization is recommended for patients who have viability in at least 25% of the left ventricular segments.
Spinal cord protection in aortic surgeriesthanigai arasu
Spinal cord protection is important during aortic surgeries to prevent neurological deficits. The risk is highest with open thoracoabdominal aortic aneurysm (TAAA) repair. Techniques to protect the spinal cord include minimizing ischemia time, increasing cord tolerance through hypothermia, augmenting perfusion, and monitoring for ischemia. Early detection of ischemia allows interventions like reattachment of segmental arteries or modifying perfusion to salvage the cord. While endovascular repair reduces risk compared to open surgery, open repair requires strategies like distal aortic perfusion, cerebrospinal fluid drainage and evoked potential monitoring to optimize spinal cord protection.
This document discusses the importance of assessing left atrial function using echocardiography. Left atrial volume and strain are superior to other echocardiographic markers for diagnosing left ventricular diastolic dysfunction. Left atrial reservoir strain in particular shows high specificity but relative low sensitivity for diagnosing heart failure with preserved ejection fraction compared to invasive exercise assessment. More research is still needed to establish robust clinical data on using left atrial function metrics for diagnosis.
Left ventricular false tendons (LVFTs) are fibromuscular
structures, connecting the left ventricular
free wall or papillary muscle and the ventricular
septum.
There is some discussion about safety issues during
intense exercise in athletes with LVFTs, as these
bands have been associated with ventricular arrhythmias
and abnormal cardiac remodelling. However,
presence of LVFTs appears to be much more common
than previously noted as imaging techniques
have improved and the association between LVFTs
and abnormal remodelling could very well be explained
by better visibility in a dilated left ventricular
lumen.
Although LVFTsmay result in electrocardiographic abnormalities
and could form a substrate for ventricular
arrhythmias, it should be considered as a normal
anatomic variant. Persons with LVFTs do not appear
to have increased risk for ventricular arrhythmias or
sudden cardiac death.
Echocardiography is a key tool for diagnosing and evaluating mitral stenosis (MS). It is essential to use an integrative approach when grading MS severity by combining Doppler, 2D imaging, and measurements, rather than relying on one alone. Echocardiography plays a major role in MS by confirming diagnosis, quantifying severity, analyzing consequences, and examining valve anatomy. Mitral valve planimetry directly measures valve area and is considered the reference standard, but additional measurements like pressure gradient and half-time are also useful. Echocardiography aids clinical decision making for patients with MS.
The document discusses assessment of mechanical dyssynchrony for cardiac resynchronization therapy. It defines electrical and mechanical dyssynchrony, and describes the deleterious hemodynamic effects of left ventricular dyssynchrony. It then summarizes various echocardiographic tools for assessing atrioventricular dyssynchrony, interventricular dyssynchrony, and intraventricular dyssynchrony, including M-mode, tissue Doppler imaging, and three-dimensional echocardiography. Measurement techniques for different dyssynchrony parameters such as septal-posterior wall motion delay, lateral wall postsystolic displacement, and time to peak systolic velocity are outlined.
The document discusses the management of a failing right ventricle in pulmonary arterial hypertension (PAH). It begins by describing the natural history of idiopathic PAH and the predictors of survival. It then discusses the physiology of the right ventricle, how it is linked to the left ventricle, and the determinants of right ventricular function. The document concludes by outlining the goals and general management strategies for chronic and acute right ventricular failure in PAH.
FFR GUIDED MULTIVESSEL ANGIOPLASTY IN MIShivani Rao
This document discusses a randomized clinical trial called Compare-Acute that examined whether an FFR-guided strategy to treat non-infarct related lesions in patients with STEMI and multivessel disease is superior to treating only the infarct-related artery. The trial enrolled 885 patients across 24 centers in Europe and Asia. Patients were randomized 1:2 to either complete FFR-guided revascularization or treatment of just the infarct artery. The primary outcome was a composite of death, myocardial infarction, or ischemia-driven revascularization at 1 year.
Echo assessment of coronary artery diseaseNizam Uddin
This document discusses the use of echocardiography to evaluate coronary artery disease. Echocardiography can detect regional wall motion abnormalities caused by acute myocardial ischemia or infarction. It is useful for identifying patients with suspected coronary artery disease or acute coronary syndrome. Echocardiography can assess left ventricular systolic function, detect regional dysfunction, and has prognostic value for patients with acute or chronic coronary artery disease. When combined with stress testing, echocardiography can identify myocardial ischemia and viability.
This document provides an overview of mechanical circulatory support devices. It discusses the evolution of such devices and their terminology. Temporary devices discussed include intra-aortic balloon pumps and Impella pumps. Long-term devices discussed include pulsatile flow devices like HeartMate I as well as continuous flow devices like HeartMate II, HeartWare HVAD, and HeartMate 3. Clinical trials are summarized that evaluated these devices as bridges to transplant or destination therapy. Biventricular support devices like the total artificial heart are also covered. The document concludes with recommendations from organizations on the use of these devices.
This study evaluated a novel transcatheter interatrial shunt device for treating heart failure with preserved ejection fraction (HFPEF). 64 patients underwent successful implantation of the device. At 6 months follow up, 71% of patients had a reduction in pulmonary capillary wedge pressure at rest or during exercise compared to baseline. The procedure was well tolerated with no safety issues. The results suggest the device may help reduce left atrial pressure and improve functional status for patients with HFPEF, though the study had limitations as an open-label single-arm trial with short follow up.
Cabg is superior to pci in heart failure patients with multivessel disease co...drucsamal
PCI is a good alternative to CABG for revascularization in patients with heart failure and viable myocardium. Revascularization of viable myocardium may improve left ventricular function and remodeling, as well as quality of life and survival. While CABG is technically straightforward and evidence-based, PCI has less risk for patients with heart failure despite being technically challenging. More research is still needed comparing PCI to CABG and medical therapy alone for chronic heart failure. Treatment must be individualized based on patient characteristics and local clinical expertise.
This document discusses mitral valve disease and treatment options such as surgical repair/replacement and the MitraClip procedure. Some key points:
- Mitral regurgitation (MR) is the most common valve problem and increases in prevalence with age. Left untreated, MR can lead to heart failure and death.
- Surgical treatment has traditionally been the only option to reliably reduce MR, but many patients are considered too high-risk for surgery.
- The MitraClip procedure is a minimally invasive treatment that fills this gap for inoperable patients by using a clip to repair the mitral valve and reduce MR without open heart surgery.
- Clinical trials show the MitraClip procedure reduces MR
The document discusses acute right ventricular (RV) failure, including:
1) The RV's main job is to maintain low right atrial pressure to optimize venous return to the heart. RV dysfunction can lead to reduced cardiac output.
2) Treatment for RV failure differs from left ventricular failure - RV failure may require fluid administration while left sided failure uses diuretics.
3) RV infarction is associated with worse outcomes than left ventricular infarction such as higher mortality, and requires a tailored treatment approach including fluid administration in some cases rather than diuretics. Early revascularization can help recovery.
This document discusses the differences between CABG (coronary artery bypass grafting) and PCI (percutaneous coronary intervention) for treating multivessel coronary artery disease. It notes that both procedures are established treatments, but that factors like mortality benefit, quality of life improvements, costs, and long-term effects need to be considered. The concept of "functional angioplasty" and using FFR (fractional flow reserve) to accurately evaluate clinical ischemia in the catheterization lab are introduced as ways to optimize outcomes from PCI. Several studies comparing outcomes of FFR-guided versus angiography-guided PCI are summarized. The document also discusses unfavorable aspects of CABG like invasiveness and long-term graft failure
The document discusses techniques for coronary artery bypass grafting and saphenous vein grafts. It summarizes a randomized trial that compared the patency of saphenous vein grafts harvested using a no-touch technique versus radial artery grafts. The trial found that no-touch saphenous vein grafts had significantly higher patency rates at 3 years compared to radial artery grafts, at 94% versus 82% respectively. Coronary arteries grafted with no-touch saphenous veins also had higher patency rates than those grafted with radial arteries. The findings suggest the no-touch technique improves saphenous vein graft quality and increases the situations where saphenous veins may be preferable to radial arteries for coronary bypass
This document summarizes key aspects of coronary circulation and physiology. It discusses determinants of myocardial oxygen consumption and extraction, determinants of coronary blood flow, phasic variations in coronary flow, autoregulation, and transmural variations. It also covers coronary flow reserve, limitations of using epicardial stenosis measurements alone, effects of microcirculation on fractional flow reserve and angiographic indices, and validation of fractional flow reserve compared to non-invasive testing and outcomes with medical therapy versus revascularization in the "gray zone".
Revascularization in heart faliure seminarAnkit Jain
This document discusses revascularization in patients with heart failure due to coronary artery disease and residual left ventricular dysfunction. It provides details on myocardial hibernation and stunning - two states of sustained contractile dysfunction despite viable myocardium. Revascularization can lead to improved survival and reverse remodeling in such patients if a sufficient amount of viable myocardium is present. Techniques to assess myocardial viability include stress echocardiography, nuclear imaging with SPECT or PET, and cardiac magnetic resonance. Revascularization is recommended for patients who have viability in at least 25% of the left ventricular segments.
Spinal cord protection in aortic surgeriesthanigai arasu
Spinal cord protection is important during aortic surgeries to prevent neurological deficits. The risk is highest with open thoracoabdominal aortic aneurysm (TAAA) repair. Techniques to protect the spinal cord include minimizing ischemia time, increasing cord tolerance through hypothermia, augmenting perfusion, and monitoring for ischemia. Early detection of ischemia allows interventions like reattachment of segmental arteries or modifying perfusion to salvage the cord. While endovascular repair reduces risk compared to open surgery, open repair requires strategies like distal aortic perfusion, cerebrospinal fluid drainage and evoked potential monitoring to optimize spinal cord protection.
This document discusses the importance of assessing left atrial function using echocardiography. Left atrial volume and strain are superior to other echocardiographic markers for diagnosing left ventricular diastolic dysfunction. Left atrial reservoir strain in particular shows high specificity but relative low sensitivity for diagnosing heart failure with preserved ejection fraction compared to invasive exercise assessment. More research is still needed to establish robust clinical data on using left atrial function metrics for diagnosis.
Left ventricular false tendons (LVFTs) are fibromuscular
structures, connecting the left ventricular
free wall or papillary muscle and the ventricular
septum.
There is some discussion about safety issues during
intense exercise in athletes with LVFTs, as these
bands have been associated with ventricular arrhythmias
and abnormal cardiac remodelling. However,
presence of LVFTs appears to be much more common
than previously noted as imaging techniques
have improved and the association between LVFTs
and abnormal remodelling could very well be explained
by better visibility in a dilated left ventricular
lumen.
Although LVFTsmay result in electrocardiographic abnormalities
and could form a substrate for ventricular
arrhythmias, it should be considered as a normal
anatomic variant. Persons with LVFTs do not appear
to have increased risk for ventricular arrhythmias or
sudden cardiac death.
Echocardiography is a key tool for diagnosing and evaluating mitral stenosis (MS). It is essential to use an integrative approach when grading MS severity by combining Doppler, 2D imaging, and measurements, rather than relying on one alone. Echocardiography plays a major role in MS by confirming diagnosis, quantifying severity, analyzing consequences, and examining valve anatomy. Mitral valve planimetry directly measures valve area and is considered the reference standard, but additional measurements like pressure gradient and half-time are also useful. Echocardiography aids clinical decision making for patients with MS.
The document discusses assessment of mechanical dyssynchrony for cardiac resynchronization therapy. It defines electrical and mechanical dyssynchrony, and describes the deleterious hemodynamic effects of left ventricular dyssynchrony. It then summarizes various echocardiographic tools for assessing atrioventricular dyssynchrony, interventricular dyssynchrony, and intraventricular dyssynchrony, including M-mode, tissue Doppler imaging, and three-dimensional echocardiography. Measurement techniques for different dyssynchrony parameters such as septal-posterior wall motion delay, lateral wall postsystolic displacement, and time to peak systolic velocity are outlined.
The document discusses the management of a failing right ventricle in pulmonary arterial hypertension (PAH). It begins by describing the natural history of idiopathic PAH and the predictors of survival. It then discusses the physiology of the right ventricle, how it is linked to the left ventricle, and the determinants of right ventricular function. The document concludes by outlining the goals and general management strategies for chronic and acute right ventricular failure in PAH.
FFR GUIDED MULTIVESSEL ANGIOPLASTY IN MIShivani Rao
This document discusses a randomized clinical trial called Compare-Acute that examined whether an FFR-guided strategy to treat non-infarct related lesions in patients with STEMI and multivessel disease is superior to treating only the infarct-related artery. The trial enrolled 885 patients across 24 centers in Europe and Asia. Patients were randomized 1:2 to either complete FFR-guided revascularization or treatment of just the infarct artery. The primary outcome was a composite of death, myocardial infarction, or ischemia-driven revascularization at 1 year.
Echo assessment of coronary artery diseaseNizam Uddin
This document discusses the use of echocardiography to evaluate coronary artery disease. Echocardiography can detect regional wall motion abnormalities caused by acute myocardial ischemia or infarction. It is useful for identifying patients with suspected coronary artery disease or acute coronary syndrome. Echocardiography can assess left ventricular systolic function, detect regional dysfunction, and has prognostic value for patients with acute or chronic coronary artery disease. When combined with stress testing, echocardiography can identify myocardial ischemia and viability.
This document provides an overview of mechanical circulatory support devices. It discusses the evolution of such devices and their terminology. Temporary devices discussed include intra-aortic balloon pumps and Impella pumps. Long-term devices discussed include pulsatile flow devices like HeartMate I as well as continuous flow devices like HeartMate II, HeartWare HVAD, and HeartMate 3. Clinical trials are summarized that evaluated these devices as bridges to transplant or destination therapy. Biventricular support devices like the total artificial heart are also covered. The document concludes with recommendations from organizations on the use of these devices.
This study evaluated a novel transcatheter interatrial shunt device for treating heart failure with preserved ejection fraction (HFPEF). 64 patients underwent successful implantation of the device. At 6 months follow up, 71% of patients had a reduction in pulmonary capillary wedge pressure at rest or during exercise compared to baseline. The procedure was well tolerated with no safety issues. The results suggest the device may help reduce left atrial pressure and improve functional status for patients with HFPEF, though the study had limitations as an open-label single-arm trial with short follow up.
Cabg is superior to pci in heart failure patients with multivessel disease co...drucsamal
PCI is a good alternative to CABG for revascularization in patients with heart failure and viable myocardium. Revascularization of viable myocardium may improve left ventricular function and remodeling, as well as quality of life and survival. While CABG is technically straightforward and evidence-based, PCI has less risk for patients with heart failure despite being technically challenging. More research is still needed comparing PCI to CABG and medical therapy alone for chronic heart failure. Treatment must be individualized based on patient characteristics and local clinical expertise.
This document discusses mitral valve disease and treatment options such as surgical repair/replacement and the MitraClip procedure. Some key points:
- Mitral regurgitation (MR) is the most common valve problem and increases in prevalence with age. Left untreated, MR can lead to heart failure and death.
- Surgical treatment has traditionally been the only option to reliably reduce MR, but many patients are considered too high-risk for surgery.
- The MitraClip procedure is a minimally invasive treatment that fills this gap for inoperable patients by using a clip to repair the mitral valve and reduce MR without open heart surgery.
- Clinical trials show the MitraClip procedure reduces MR
The document discusses acute right ventricular (RV) failure, including:
1) The RV's main job is to maintain low right atrial pressure to optimize venous return to the heart. RV dysfunction can lead to reduced cardiac output.
2) Treatment for RV failure differs from left ventricular failure - RV failure may require fluid administration while left sided failure uses diuretics.
3) RV infarction is associated with worse outcomes than left ventricular infarction such as higher mortality, and requires a tailored treatment approach including fluid administration in some cases rather than diuretics. Early revascularization can help recovery.
This document discusses the differences between CABG (coronary artery bypass grafting) and PCI (percutaneous coronary intervention) for treating multivessel coronary artery disease. It notes that both procedures are established treatments, but that factors like mortality benefit, quality of life improvements, costs, and long-term effects need to be considered. The concept of "functional angioplasty" and using FFR (fractional flow reserve) to accurately evaluate clinical ischemia in the catheterization lab are introduced as ways to optimize outcomes from PCI. Several studies comparing outcomes of FFR-guided versus angiography-guided PCI are summarized. The document also discusses unfavorable aspects of CABG like invasiveness and long-term graft failure
The document discusses techniques for coronary artery bypass grafting and saphenous vein grafts. It summarizes a randomized trial that compared the patency of saphenous vein grafts harvested using a no-touch technique versus radial artery grafts. The trial found that no-touch saphenous vein grafts had significantly higher patency rates at 3 years compared to radial artery grafts, at 94% versus 82% respectively. Coronary arteries grafted with no-touch saphenous veins also had higher patency rates than those grafted with radial arteries. The findings suggest the no-touch technique improves saphenous vein graft quality and increases the situations where saphenous veins may be preferable to radial arteries for coronary bypass
This document summarizes key aspects of coronary circulation and physiology. It discusses determinants of myocardial oxygen consumption and extraction, determinants of coronary blood flow, phasic variations in coronary flow, autoregulation, and transmural variations. It also covers coronary flow reserve, limitations of using epicardial stenosis measurements alone, effects of microcirculation on fractional flow reserve and angiographic indices, and validation of fractional flow reserve compared to non-invasive testing and outcomes with medical therapy versus revascularization in the "gray zone".
Invasive coronary physiology to select patients for coronary revascularisation has become established in contemporary guidelines for the management of stable coronary artery disease. Compared to revascularisation based on angiography alone, the use of coronary physiology has been shown to improve clinical outcomes and cost efficiency. However, recent data from randomised controlled trials have cast doubt upon
the value of ischaemia testing to select patients for revascularisation. Importantly, 20-40% of patients have
persistence or recurrence of angina after angiographically successful percutaneous coronary intervention
(PCI). This state-of-the-art review is focused on the transitioning role of invasive coronary physiology from
its use as a dichotomous test for ischaemia with fixed cut-points, towards its utility for real-time guidance of PCI to optimise physiological results. We summarise the contemporary evidence base for ischaemia testing
in stable coronary artery disease, examine emerging indices which allow advanced physiological guidance
of PCI, and discuss the rationale and evidence base for post-PCI physiological assessments to assess the success of revascularisation.
1) The study evaluated 5 types of contemporary drug-eluting stents used in 6,645 patients undergoing complex high-risk procedures. Target vessel failure was lowest with ultrathin sirolimus-eluting stents.
2) Echocardiographic markers of congestion including E/e', tricuspid regurgitation velocity, and inferior vena cava collapsibility predicted outcomes in 505 heart failure patients, both with and without atrial fibrillation. Higher congestion grade was associated with increased risk of cardiovascular death or hospitalization.
3) Right-sided congestion measures may provide prognostic value beyond clinical factors and natriuretic peptides in heart failure with preserved ejection fraction
This document discusses using intrathoracic impedance measures from implantable cardiac devices to monitor changes in intravascular fluid volume during volume reduction therapy for heart failure patients. It found that two impedance vectors, between the right atrial ring to left ventricular ring and the left ventricular ring to right ventricular ring, were most closely associated with changes in plasma volume as measured by hematocrit levels. Monitoring these specific impedance vectors may help more accurately guide volume reduction therapy by tracking changes in the intravascular fluid compartment.
This document provides guidelines on measuring heart rate variability (HRV). It discusses that HRV analysis allows evaluation of autonomic nervous system influence on the heart through variations in beat-to-beat heart rate. The document establishes standards for HRV measurement methods including time domain methods using statistical analyses of normal-to-normal heart rate intervals, frequency domain methods using power spectral analysis, and geometrical methods analyzing heart rate patterns. The goals are to standardize terminology, specify measurement methods, define physiological interpretations, describe clinical applications, and identify areas for future research to ensure appropriate use and understanding of HRV.
This document summarizes a literature review on the effect of hemiparesis on blood pressure measurements. Several studies found that blood pressure was often higher in the hemiparetic arm compared to the non-affected arm, especially if the hemiparetic arm had increased muscle tone. However, other studies found blood pressure could also be lower in the hemiparetic arm, especially if it was flaccid. The literature review concluded that the best practice is to measure blood pressure in both arms to identify any interarm differences, as blood pressure can be either higher or lower in the hemiparetic arm. It recommends reminding nurses to measure blood pressure in both arms for stroke patients.
This document summarizes various physiological indices used to assess coronary lesions, including fractional flow reserve (FFR), coronary flow reserve (CFR), and instantaneous wave-free ratio (iFR). It describes how FFR is measured by taking the ratio of distal coronary pressure to aortic pressure during maximal hyperemia. FFR of 0.8 or below indicates a functionally significant stenosis. The document also reviews evidence from major trials supporting the clinical use of FFR and discusses its application in different coronary lesion scenarios.
Guidelines heart rate_variability_ft_1996[1]ES-Teck India
Guidelines
Heart rate variability
Standards of measurement, physiological interpretation, and
clinical use
Task Force of The European Society of Cardiology and The North American
Society of Pacing and Electrophysiology (Membership of the Task Force listed in
the Appendix)
This study examined the physiological responses to progressive reductions in central blood volume from lower body negative pressure (LBNP) in 116 subjects with high tolerance. The subjects were divided into two groups based on their cardiac baroreflex sensitivity (BRS) at the point of presyncope: Group 1 had a BRS over 1.0 and Group 2 had a BRS under 1.0. Contrary to the hypothesis, Group 1 demonstrated lower heart rate, higher stroke volume, less sympathetic nerve activity, and less increase in peripheral vascular resistance compared to Group 2, despite both groups having similar tolerance times, blood pressure levels, and cardiac output at presyncope. This suggests variability in individual physiological strategies for compensating for reduced central blood
This document discusses a study evaluating the incidence, predictors, and long-term outcomes of patients experiencing in-stent restenosis (ISR) after receiving long drug-eluting stents for coronary arteries. 421 patients received long drug-eluting stents and 371 patients underwent follow up. The overall incidence of ISR was 4%. Risk factors for ISR included diabetes and long lesions. Of those with ISR, 40% underwent repeat PCI, 46.7% underwent bypass surgery, and 13.3% were treated medically. During long-term follow up of 12-26 months, there were no deaths from ISR and the incidence of major adverse cardiac events was low. ISR did not
This document provides an updated summary of guidelines for blood conservation in cardiac surgery from The Society of Thoracic Surgeons and the Society of Cardiovascular Anesthesiologists. Major revisions include new recommendations regarding dual anti-platelet therapy management before surgery, drugs that augment red blood cell volume or limit blood loss, blood derivatives, blood salvage management, minimally invasive procedures, extracorporeal membrane oxygenation, hemostatic agents, and insights into team-based interventions. The guidelines were updated based on a literature review using standardized search terms to ensure the recommendations reflect the most current evidence available.
1) A study examined 103 heart attack patients treated with high-dose statins and found plaque volume decreased slightly (0.9%) in the arteries not responsible for the heart attack.
2) A randomized study of 296 heart attack patients found that performing revascularization of additional blocked arteries beyond the heart attack artery led to fewer total cardiac events (10% vs 21%) over 12 months compared to only treating the heart attack artery.
3) A study of 738 patients with chronic total blockages and good collateral blood flow found that revascularizing the blockages reduced cardiac death and total cardiac events compared to medical treatment alone, showing benefit of revascularization even in patients with established collateral circulation.
This document discusses various interventional therapies for resistant hypertension and renal artery stenosis, including renal sympathetic nerve ablation (RDN), baroreceptor activation therapy (BAT), and arteriovenous shunt creation. It provides details on techniques such as radiofrequency ablation and ultrasound ablation for RDN. It outlines trial results showing reductions in blood pressure from RDN, BAT, and arteriovenous shunts. It also discusses limitations of renal artery stenting based on recent trials. In summary, the document reviews novel interventional approaches for treating difficult cases of high blood pressure.
This multi-center randomized controlled trial compared perioperative hemodynamic goal-directed therapy (GDT) using pulse pressure variation and cardiac index trending to standard care in 160 patients undergoing major abdominal surgery. Patients in the GDT group had fewer total complications and fewer infections compared to the control group. There were no significant differences in length of hospital stay, return of bowel function, or PACU length of stay between the two groups. GDT using pulse pressure variation and cardiac index trending reduces postoperative complications after major abdominal surgery.
This study examined data from an implantable hemodynamic monitor in 32 heart failure patients over 9 months without using the data for management, and then over 17 months where the data was incorporated into management. The study found that right ventricular pressures increased before volume overload events requiring hospitalization. After using the hemodynamic data for management, hospitalizations decreased by 57% compared to the previous year. Long-term hemodynamic monitoring may help guide heart failure management and reduce hospitalizations.
LONG-TERM OUTCOMES OF PATENT FORAMEN OVALE 1.pptxddocofdera
PFO closure with the Amplatzer device was found to be associated with a lower risk of recurrent ischemic stroke compared to medical therapy alone in patients aged 18-60 who experienced a cryptogenic stroke. Over a median follow up of 5.9 years, the rate of recurrent stroke was 0.58 events per 100 patient-years in the PFO closure group versus 1.07 events in the medical therapy group. However, PFO closure was also associated with a higher rate of venous thromboembolism such as pulmonary embolism and deep vein thrombosis compared to medical therapy.
Short term tranexamic acid reduced in hospital mortalityYoga Rossi
This research article compares outcomes of patients with aneurysmal subarachnoid hemorrhage (aSAH) treated with either standard care or additional short-term tranexamic acid (TXA) treatment. Data was pooled from two Dutch hospitals between 2012-2015, with 119 patients receiving TXA and 390 receiving standard care. While TXA treatment did not reduce recurrent bleeding rates, it was associated with a lower in-hospital mortality rate compared to standard care alone. Six-month clinical outcomes as measured by modified Rankin Scale scores were similar between the two groups.
A 57-year-old woman was admitted to the hospital with chest pain. Electrocardiograms and troponin levels were normal. Intravascular ultrasound was performed before placing a stent in the left main coronary artery and left anterior descending artery to treat a blockage. The minimum lumen area increased to 4.24mm x 4.13mm after stenting.
Congenital defects can put a strain on the heart, causing it to work harder. To stop your heart from getting weaker with this extra work, your doctor may try to treat you with medications. They are aimed at easing the burden on the heart muscle. You need to control your blood pressure if you have any type of heart problem.
Changing your lifestyle can help control and manage high blood pressure. Your health care provider may recommend that you make lifestyle changes including:
Eating a heart-healthy diet with less salt
Getting regular physical activity
Maintaining a healthy weight or losing weight
Limiting alcohol
Not smoking
Getting 7 to 9 hours of sleep daily
CRISPR technologies have progressed by leaps and bounds over the past decade, not only having a transformative effect on
biomedical research but also yielding new therapies that are poised to enter the clinic. In this review, I give an overview of (i)
the various CRISPR DNA-editing technologies, including standard nuclease gene editing, base editing, prime editing, and epigenome editing, (ii) their impact on cardiovascular basic science research, including animal models, human pluripotent stem
cell models, and functional screens, and (iii) emerging therapeutic applications for patients with cardiovascular diseases, focusing on the examples of Hypercholesterolemia, transthyretin amyloidosis, and Duchenne muscular dystrophy.
This case report describes a patient who underwent seven operations over one year to treat recurrent pacemaker pocket infections. The patient had undergone a splenectomy seven years prior due to a splenic rupture from a traffic accident. This left the patient immunocompromised and at higher risk for infection. The patient later required a pacemaker implantation for complete heart block. The pacemaker pocket developed repeated infections, likely due to the patient's asplenic state impairing immunity. The infections were difficult to treat due to multiple complicating factors, including an abandoned pacemaker lead and reuse of a sterilized pacemaker. This highlights the influence of patient factors like asplenia on procedural outcomes like pacemaker implantation.
Transcatheter closure of patent ductus arteriosus (PDA) is feasible in low-birth-weight infants. A female baby was born prematurely with a birth weight of 924 g. She had a PDA measuring 3.7 mm. She was dependent on positive pressure ventilation for congestive heart failure in addition to the heart failure medications. She could not be discharged from the hospital even after 79 days of birth, and even though her weight reached 1.9 kg in the neonatal intensive care unit. We attempted to plug the PDA using an Amplatzer Piccolo Occluder, but the device failed to anchor. Then, the PDA was plugged using a 4-6 Amplatzer Duct Occluder using a 6-Fr sheath which was challenging.
Accidental misplacement of the limb lead electrodes is a common cause of ECG abnormality and may simulate pathology such as ectopic atrial rhythm, chamber enlargement or myocardial ischaemia and infarction
A Case of Device Closure of an Eccentric Atrial Septal Defect Using a Large D...Ramachandra Barik
Device closure of an eccentric atrial septal defect can be challenging and needs technical modifications to avoid unnecessary complications. Here, we present a case of a 45-year-old woman who underwent device closure of an eccentric defect with a large device. The patient developed pericardial effusion and left-sided pleural effusion due to injury to the junction of right atrium and superior vena cava because of the malalignment of the delivery sheath and left atrial disc before the device was pulled across the eccentric defect despite releasing the left atrial disc in the left atrium in place of the left pulmonary vein. These two serious complications were managed conservatively with close monitoring of the case during and after the procedure.
1) Bradycardia can be caused by abnormalities in the conduction system or autonomic nervous system. The conduction system includes the sinus node, AV node, His-Purkinje system and different types of heart block can occur when impulses are blocked at different locations.
2) There are three main types of AV block - first degree, second degree (Mobitz types I and II), and third degree. High grade AV block involves blockage of two or more consecutive impulses.
3) Third degree or complete heart block results in complete dissociation between the atria and ventricles with independent pacemakers. It can occur at the AV node or below in the His-Purkin
1. Bradycardia is defined as a resting heart rate below 50 beats per minute. It can be physiological or pathological.
2. Sinus bradycardia originates from the sinus node and has a normal P wave morphology with a prolonged PR interval. It can be caused by increased vagal tone, medications, or hypothyroidism.
3. Sick sinus syndrome is characterized by sinus bradycardia, sinus arrest, or combinations of sinus node and AV node dysfunction. It may involve intermittent bradycardia and tachycardia. Pacemaker implantation is usually treatment.
This document discusses ventricular arrhythmias including their origins, characteristics, classifications, and causes. It provides details on:
- The sites of origin for supraventricular tachycardia (SVT) and ventricular arrhythmias.
- Characteristics that distinguish SVT from ventricular arrhythmias such as QRS width.
- Classifications of ventricular arrhythmias including premature ventricular complexes, ventricular tachycardia, fibrillation, and electrical storm.
- Causes and characteristics of different types of ventricular tachycardia such as monomorphic VT, polymorphic VT, and torsades de pointes.
- Investigations and treatments for ventricular arrhythmias including cardiac imaging
This document provides information on supraventricular tachycardia (SVT), including:
- The anatomy and conduction system of the heart that is relevant to SVT.
- The mechanisms that can cause cardiac arrhythmias, including disorders of impulse formation, conduction, and combinations of the two.
- Characteristics used to classify different types of arrhythmias based on rate, rhythm, site of origin, and QRS morphology.
- Specific types of SVT like atrial fibrillation, AV nodal reentry tachycardia, and accessory pathway mediated tachycardias.
- Methods for diagnosing and treating SVT such as electrophysiology studies, catheter ablation
Trio of Rheumatic Mitral Stenosis, Right Posterior Septal Accessory Pathway a...Ramachandra Barik
A 57-year-old male presented with recurrent palpitations. He was diagnosed with rheumatic mitral stenosis, right posterior septal accessory pathway and atrial flutter. An electrophysiological study after percutaneous balloon mitral valvotomy showed that the palpitations were due to atrial flutter with right bundle branch aberrancy. The right posterior septal pathway was a bystander because it had a higher refractory period than the atrioventricular node.
This document discusses anticoagulation therapy options during pregnancy for different cardiac conditions. It notes that vitamin K antagonists (VKAs) should be avoided in the first trimester due to risk of embryopathy but can be used in the second and third trimester with risks of 0.7-2% of foetopathy. Unfractionated heparin does not cross the placenta but its use throughout pregnancy is not recommended due to risk of foetopathy. Low molecular weight heparin is considered the safest option for anticoagulation in weeks 6-12 when risk of embryopathy is a concern and has not been associated with risk of foetopathy. Fondaparinux use should be limited
Percutaneous balloon dilatation, first described by
Andreas Gruentzig in 1979, was initially performed
without the use of guidewires.1 The prototype
balloon catheter was developed as a double lumen
catheter (one lumen for pressure monitoring or
distal perfusion, the other lumen for balloon inflation/deflation) with a short fixed and atraumatic
guidewire at the tip. Indeed, initially the technique
involved advancing a rather rigid balloon catheter
freely without much torque control into a coronary
artery. Bends, tortuosities, angulations, bifurcations,
and eccentric lesions could hardly, if at all, be negotiated, resulting in a rather frustrating low procedural success rate whenever the initial limited
indications (proximal, short, concentric, noncalcified) were negated.2 Luck was almost as
important as expertise, not only for the operator,
but also for the patient. It is to the merit of
Simpson who, in 1982, introduced the novelty of
advancing the balloon catheter over a removable
guidewire, which had first been advanced in the
target vessel.3 This major technical improvement
resulted overnight in a notable increase in the procedural success rate. Guidewires have since evolved
into very sophisticated devices.
Optical coherence tomography-guided algorithm for percutaneous coronary intervention. Vessel diameter should be assessed using the external elastic lamina (EEL)-EEL diameter at the reference segments, and rounded down to select interventional devices (balloons, stents). If the EEL cannot be identified, luminal measures are used and rounded up to 0.5 mm larger for selection of the devices. Optical coherence tomography (OCT)-guided optimisation strategies post stent implantation per EEL-based diameter measurement and per lumen-based diameter measurement are shown. For instance, if the distal EEL-EEL diameter measures 3.2 mm×3.1 mm (i.e., the mean EEL-based diameter is 3.15 mm), this number is rounded down to the next available stent size and post-dilation balloon to be used at the distal segment. Thus, a 3.0 mm stent and non-compliant balloon diameter is selected. If the proximal EEL cannot be visualised, the mean lumen diameter should be used for device sizing. For instance, if the mean proximal lumen diameter measures 3.4 mm, this number is rounded up to the next available balloon diameter (within up to 0.5 mm larger) for post-dilation. MLA: minimal lumen area; MSA: minimal stent area;NC: non-compliant
Brugada syndrome (BrS) is an inherited cardiac disorder,
characterised by a typical ECG pattern and an increased
risk of arrhythmias and sudden cardiac death (SCD).
BrS is a challenging entity, in regard to diagnosis as
well as arrhythmia risk prediction and management.
Nowadays, asymptomatic patients represent the majority
of newly diagnosed patients with BrS, and its incidence
is expected to rise due to (genetic) family screening.
Progress in our understanding of the genetic and
molecular pathophysiology is limited by the absence
of a true gold standard, with consensus on its clinical
definition changing over time. Nevertheless, novel
insights continue to arise from detailed and in-depth
studies, including the complex genetic and molecular
basis. This includes the increasingly recognised
relevance of an underlying structural substrate. Risk
stratification in patients with BrS remains challenging,
particularly in those who are asymptomatic, but recent
studies have demonstrated the potential usefulness
of risk scores to identify patients at high risk of
arrhythmia and SCD. Development and validation of
a model that incorporates clinical and genetic factors,
comorbidities, age and gender, and environmental
aspects may facilitate improved prediction of disease
expressivity and arrhythmia/SCD risk, and potentially
guide patient management and therapy. This review
provides an update of the diagnosis, pathophysiology
and management of BrS, and discusses its future
perspectives.
The Human Developmental Cell Atlas (HDCA) initiative, which is part of the Human Cell Atlas, aims to create a comprehensive reference map of cells during development. This will be critical to understanding normal organogenesis, the effect of mutations, environmental factors and infectious agents on human development, congenital and childhood disorders, and the cellular basis of ageing, cancer and regenerative medicine. Here we outline the HDCA initiative and the challenges of mapping and modelling human development using state-of-the-art technologies to create a reference atlas across gestation. Similar to the Human Genome Project, the HDCA will integrate the output from a growing community of scientists who are mapping human development into a unified atlas. We describe the early milestones that have been achieved and the use of human stem-cell-derived cultures, organoids and animal models to inform the HDCA, especially for prenatal tissues that are hard to acquire. Finally, we provide a roadmap towards a complete atlas of human development.
The treatment of patients with advanced acute heart failure is still challenging.
Intra-aortic balloon pump (IABP) has widely been used in the management of
patients with cardiogenic shock. However, according to international guidelines, its
routinary use in patients with cardiogenic shock is not recommended. This recommendation is derived from the results of the IABP-SHOCK II trial, which demonstrated
that IABP does not reduce all-cause mortality in patients with acute myocardial infarction and cardiogenic shock. The present position paper, released by the Italian
Association of Hospital Cardiologists, reviews the available data derived from clinical
studies. It also provides practical recommendations for the optimal use of IABP in
the treatment of cardiogenic shock and advanced acute heart failure.
PGx Analysis in VarSeq: A User’s PerspectiveGolden Helix
Since our release of the PGx capabilities in VarSeq, we’ve had a few months to gather some insights from various use cases. Some users approach PGx workflows by means of array genotyping or what seems to be a growing trend of adding the star allele calling to the existing NGS pipeline for whole genome data. Luckily, both approaches are supported with the VarSeq software platform. The genotyping method being used will also dictate what the scope of the tertiary analysis will be. For example, are your PGx reports a standalone pipeline or would your lab’s goal be to handle a dual-purpose workflow and report on PGx + Diagnostic findings.
The purpose of this webcast is to:
Discuss and demonstrate the approaches with array and NGS genotyping methods for star allele calling to prep for downstream analysis.
Following genotyping, explore alternative tertiary workflow concepts in VarSeq to handle PGx reporting.
Moreover, we will include insights users will need to consider when validating their PGx workflow for all possible star alleles and options you have for automating your PGx analysis for large number of samples. Please join us for a session dedicated to the application of star allele genotyping and subsequent PGx workflows in our VarSeq software.
Summer is a time for fun in the sun, but the heat and humidity can also wreak havoc on your skin. From itchy rashes to unwanted pigmentation, several skin conditions become more prevalent during these warmer months.
The biomechanics of running involves the study of the mechanical principles underlying running movements. It includes the analysis of the running gait cycle, which consists of the stance phase (foot contact to push-off) and the swing phase (foot lift-off to next contact). Key aspects include kinematics (joint angles and movements, stride length and frequency) and kinetics (forces involved in running, including ground reaction and muscle forces). Understanding these factors helps in improving running performance, optimizing technique, and preventing injuries.
These lecture slides, by Dr Sidra Arshad, offer a simplified look into the mechanisms involved in the regulation of respiration:
Learning objectives:
1. Describe the organisation of respiratory center
2. Describe the nervous control of inspiration and respiratory rhythm
3. Describe the functions of the dorsal and respiratory groups of neurons
4. Describe the influences of the Pneumotaxic and Apneustic centers
5. Explain the role of Hering-Breur inflation reflex in regulation of inspiration
6. Explain the role of central chemoreceptors in regulation of respiration
7. Explain the role of peripheral chemoreceptors in regulation of respiration
8. Explain the regulation of respiration during exercise
9. Integrate the respiratory regulatory mechanisms
10. Describe the Cheyne-Stokes breathing
Study Resources:
1. Chapter 42, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 36, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 13, Human Physiology by Lauralee Sherwood, 9th edition
Giloy in Ayurveda - Classical Categorization and SynonymsPlanet Ayurveda
Giloy, also known as Guduchi or Amrita in classical Ayurvedic texts, is a revered herb renowned for its myriad health benefits. It is categorized as a Rasayana, meaning it has rejuvenating properties that enhance vitality and longevity. Giloy is celebrated for its ability to boost the immune system, detoxify the body, and promote overall wellness. Its anti-inflammatory, antipyretic, and antioxidant properties make it a staple in managing conditions like fever, diabetes, and stress. The versatility and efficacy of Giloy in supporting health naturally highlight its importance in Ayurveda. At Planet Ayurveda, we provide a comprehensive range of health services and 100% herbal supplements that harness the power of natural ingredients like Giloy. Our products are globally available and affordable, ensuring that everyone can benefit from the ancient wisdom of Ayurveda. If you or your loved ones are dealing with health issues, contact Planet Ayurveda at 01725214040 to book an online video consultation with our professional doctors. Let us help you achieve optimal health and wellness naturally.
NAVIGATING THE HORIZONS OF TIME LAPSE EMBRYO MONITORING.pdfRahul Sen
Time-lapse embryo monitoring is an advanced imaging technique used in IVF to continuously observe embryo development. It captures high-resolution images at regular intervals, allowing embryologists to select the most viable embryos for transfer based on detailed growth patterns. This technology enhances embryo selection, potentially increasing pregnancy success rates.
5-hydroxytryptamine or 5-HT or Serotonin is a neurotransmitter that serves a range of roles in the human body. It is sometimes referred to as the happy chemical since it promotes overall well-being and happiness.
It is mostly found in the brain, intestines, and blood platelets.
5-HT is utilised to transport messages between nerve cells, is known to be involved in smooth muscle contraction, and adds to overall well-being and pleasure, among other benefits. 5-HT regulates the body's sleep-wake cycles and internal clock by acting as a precursor to melatonin.
It is hypothesised to regulate hunger, emotions, motor, cognitive, and autonomic processes.
Pictorial and detailed description of patellar instability with sign and symptoms and how to diagnose , what investigations you should go with and how to approach with treatment options . I have presented this slide in my 2nd year junior residency in orthopedics at LLRM medical college Meerut and got good reviews for it
After getting it read you will definitely understand the topic.
How to Control Your Asthma Tips by gokuldas hospital.Gokuldas Hospital
Respiratory issues like asthma are the most sensitive issue that is affecting millions worldwide. It hampers the daily activities leaving the body tired and breathless.
The key to a good grip on asthma is proper knowledge and management strategies. Understanding the patient-specific symptoms and carving out an effective treatment likewise is the best way to keep asthma under control.
Travel vaccination in Manchester offers comprehensive immunization services for individuals planning international trips. Expert healthcare providers administer vaccines tailored to your destination, ensuring you stay protected against various diseases. Conveniently located clinics and flexible appointment options make it easy to get the necessary shots before your journey. Stay healthy and travel with confidence by getting vaccinated in Manchester. Visit us: www.nxhealthcare.co.uk
2. Intracoronary physiologic indices enable cardiologists to
circumvent the limitations of angiography when assessing
the hemodynamic impact of stenoses (1,2). Functional
assessment of stenoses in the catheterization laboratory can
be performed by measuring intracoronary flow velocity
(coronary flow velocity reserve), pressure (fractional flow
reserve [FFR]), or both (hyperemic stenotic resistance)
(3,4). FFR is the most widely used index in clinical practice,
being supported by a large body of evidence demonstrating
See page 1403
its value in clinical decision making. When used to guide percu-
taneous interventions, FFR has been shown to improve clinical
outcomes and procedural cost-efficiency (5–7).
The cornerstone of FFR is the linear relationship be-
tween pressure and flow under conditions of constant (and
minimized) intracoronary resistance (4). Under such condi-
tions, pressure and flow are assumed to be directly propor-
tional, and a decrease in pressure across a stenosis reflects a
decrease in blood flow to the dependent myocardium.
However, even after administration of potent pharmaco-
logic agents such as adenosine, intracoronary resistance is
not static, but instead fluctuates
in a phasic pattern (akin to im-
pedance in an alternating-current
electrical circuit) throughout the
cardiac cycle (Figs. 1 and 2).
These fluctuations reflect the in-
teraction between the myocar-
dium and microvasculature dur-
ing systole (high intracoronary resistance, compression of
microvasculature) and diastole (lower intracoronary resis-
tance, decompression of the microvasculature) (8). Accord-
ingly, to minimize these effects, FFR is calculated during
hyperemia (maximal flow to the vascular bed) and time-
averaged over several cardiac cycles to ensure constant and
minimal intracoronary resistance.
Although time-averaging and the administration of phar-
macologic vasodilators were a pragmatic solution to achiev-
ing appropriate conditions in which to calculate FFR when
computational power was limited, it may now be unneces-
sary if a time period could be identified from the resting
pressure waveform when resistance is naturally constant and
minimized. Theoretically, during such a period in the cardiac
cycle, intracoronary pressure and flow would be propor-
Abbreviations
and Acronyms
FFR ؍ fractional
flow reserve
iFR ؍ instantaneous
wave-free ratio
-6
-4
-2
0
2
4
Waveintensity
(Wx10-5m-2s-2)
0
20
40
Separatedpressure
abovediastole
(mmHg)
0 100 200 300 400
100
150
200
Pressure
(mmHg)
0 100 200 300 400
0.3
0.4
0.5
1200
300
600
Resistance
(mmHgs/m)
Time (ms)
proximal-originating
compression wave
microcirculatory-originating
compression waves
proximal-originating
pressure
microcirculatory
-originating pressure
Pressure
WAVE FREE PERIOD
Flow velocity
microcirculatory-originating
decompression wave
500 600 700500 600 700
0.1
0.2
Velocity
(m/s)
A
B
C
D
Figure 1 Identification of Wave-Free Period in the Cardiac Cycle
Wave-intensity analysis (A) demonstrates the proximal and microcirculatory (distal) originating waves generated during the cardiac cycle. A wave-free period can be seen
in diastole when no new waves are generated (shaded). This corresponds to a time period in which there is minimal microcirculatory (distal)–originating pressure (B),
minimal and constant resistance (C), and a nearly constant rate of change in flow velocity (D). (Separated pressure above diastole is the residual pulsatile separated
pressure component after subtraction of the diastolic pressure.)
1393JACC Vol. 59, No. 15, 2012 Sen et al.
April 10, 2012:1392–402 Adenosine-Free Measure of Stenosis Severity
3. tional. Consequently, a ratio of trans-stenotic pressures
during this time would provide a measure of the severity of
a coronary stenosis. Identification of such a period would
negate the need for administration of pharmacologic agents
such as adenosine, saving time, reducing costs and side
effects, and leading to improved adoption in the cardiac
catheter laboratory.
In the first part of this study, we identified the existence
of a diastolic interval in which intracoronary resistance at
rest is equivalent to time-averaged resistance during FFR
measurements. We hypothesize that pressure measurements
obtained selectively at this specific interval of the cardiac cycle
would allow a new pressure-derived index of stenosis severity
that does not require pharmacologic vasodilation; we term this
the instantaneous wave-free ratio (iFR). In the second part of
the study, this hypothesis was tested in a larger population by
comparing iFR and FFR measurements.
Methods
Study population. This multicenter international, nonran-
domized study included 131 patients (age 63 Ϯ 10 years,
85% male) scheduled for coronary angiography or percuta-
neous coronary intervention at 3 sites (Imperial College
Healthcare NHS trust, London, United Kingdom; Cardio-
vascular Institute, Hospital Clı´nico San Carlos, Madrid,
Spain; and Royal Brompton and Harefield NHS trust,
London, United Kingdom). The patient demographics are
consistent with the broad entry criteria used in recruitment
(Table 1). Exclusion criteria were limited to significant
valvular pathology, previous coronary artery bypass surgery,
contraindication to adenosine administration (e.g., asthma,
chronic obstructive pulmonary disease, heart rate Ͻ50
beats/min, and systolic blood pressure Ͻ90 mm Hg),
increased troponin, and weight Ͼ200 kg. All subjects gave
written informed consent in accordance with the protocol
approved by the local ethics committee (NRES ref: 09/
H0712/102; NCT01118481).
Study protocol. CARDIAC CATHETERIZATION. In this
2-part study, patients were divided into 2 groups, providing
a total of 157 stenoses (part 1, 39 stenoses; part 2, 118
stenoses) (Fig. 3).
0
0.2
0.4
Velocity
(m/s)
50
100
150
200
Pressure
(mmHg)
0
1000
2000
Resistance
(mmHgs/m)
0 30 60
Time (s)
Figure 2 Coronary Velocity, Aortic and Coronary Pressures, and Resistance in the Right Coronary Artery
A typical example of the pressure, flow velocity, and resistance data obtained from a patient with an intermediate right coronary artery stenosis (arrow, right panel). The
effect of hyperemia can be seen with concomitant increase in flow velocity (left, top panel) and decrease in intracoronary pressure (left, middle panel), stable intracoro-
nary resistance is subsequently achieved (left, bottom panel).
Patient Demographic DataTable 1 Patient Demographic Data
Group 1:
Pressure/Flow Velocity
Group 2:
Pressure Only Overall
No. of stenoses 39 118 157
Age, yrs 64.6 Ϯ 9.9 59.2 Ϯ 16.1 62.6 Ϯ 10.2
Male 35 (89.7) 96 (81.4) 131 (83.4)
Diabetes 21 (53.9) 33 (28) 54 (34.4)
Smoker 6 (15.4) 28 (23.7) 34 (21.7)
Hypertension 23 (59) 65 (55) 88 (56.1)
Impaired LV function
(EF Ͻ50%)
4 (10.3) 9 (7.6) 13 (8.3)
Stable angina 35 (89.7) 116 (98.3) 151 (96.2)
Unstable angina 4 (10.3) 2 (1.7) 6 (3.8)
Single vessel 16 (41) 92 (78) 108 (68.8)
Multivessel 23 (59) 26 (22) 49 (31.2)
Coronary artery
LAD 21 (54.1) 48 (40.7) 69 (44)
Cx 11 (27) 32 (27.1) 43 (27.1)
RCA 7 (18.9) 38 (32.2) 45 (28.9)
Adenosine (route)
Intracoronary 0 (0) 94 (79.7) 94 (59.9)
Intravenous 39 (100) 24 (20.3) 63 (40.1)
Values are n, mean Ϯ SD, or n (%).
Cx ϭ circumflex artery; EF ϭ ejection fraction; LAD ϭ left anterior descending artery; LV ϭ left
ventricular; RCA ϭ right coronary artery.
1394 Sen et al. JACC Vol. 59, No. 15, 2012
Adenosine-Free Measure of Stenosis Severity April 10, 2012:1392–402
4. In part 1, cardiac catheterization was undertaken via the
femoral approach. After diagnostic angiography, a 0.014-
inch pressure- and Doppler sensor–tipped wire (ComboWire
XT, Volcano Corporation, San Diego, California) was
passed into the target vessel via a guiding catheter. Pressure
equalization was performed at the tip of the catheter before its
advancement distal to the stenosis. Pressure and flow velocity
recordings were then made at baseline. Adenosine was then
infused (140 g/kg/min) via a femoral venous sheath, and
pressure and flow velocity measurements repeated under con-
ditions of maximal pharmacologic vasodilation.
In part 2, cardiac catheterization was undertaken via either
the femoral or radial approach. Adenosine doses of 140
g/mg/min (via the femoral vein) or 120 g (intracoronary)
were used to induce vasodilation. After diagnostic angiogra-
phy, a 0.014-inch pressure sensor–tipped wire (PrimeWire,
Volcano Corporation, or Radi PressureWire, St. Jude Medical,
Minneapolis, Minnesota) was equalized and then advanced
distally. Pressure measurements were made at baseline and
under maximal pharmacologic vasodilation.
In both groups, 5,000 IU intravenous heparin was given at
the start of the procedure and 300 g of intracoronary nitrates
were routinely given before hemodynamic measurements.
Hemodynamic recordings. When the ComboWire or
PrimeWire pressure wire was used, the electrocardiogram,
pressures, and flow velocity signals were directly extracted
from the digital archive of the device console (ComboMap,
Volcano Corporation). When the Radi PressureWire sys-
tem was used, continuous digital acquisition and storage of
the electrocardiograms and aortic and intracoronary pres-
sures were performed using a 12-bit resolution analog-to-
digital converter (DI-200 PGL, DataQ Instruments, Ak-
ron, Ohio) controlled by dedicated software (WinDaq 200,
DataQ Instruments) in a personal computer. The sampling
rate was 114 Hz per channel.
At the end of each recording, the pressure sensor was
returned to the catheter tip to ensure that there was no
pressure drift. When drift was identified, the measurements
were repeated. Data were analyzed offline using a custom
software package designed with Matlab (Mathworks, Inc.,
Natick, Massachusetts).
Identification of period of constant and minimal resistance.
Changes in coronary hemodynamics over the cardiac cycle
were assessed by calculating instantaneous resistance and by
applying wave-intensity analysis. An index of resistance was
calculated as the ratio between pressure and flow velocity.
Wave-intensity analysis was performed according to the meth-
odology described previously (8) to identify wave-free periods
(Fig. 1A). During this wave-free period, the onset of minimal
resistance was identified and its value calculated for each
patient. It was not possible to calculate resistance in 2 patients
due to poor tracking of the velocity envelope during diastole.
Mean intracoronary resistance and its coefficient of variation
were then calculated over a minimum of 3 beats.
To minimize any selection bias and truly assess the diag-
nostic efficiency of our index, we designed this study to include
all the cardiac patients that FFR is used in routinely in clinical
practice (including single-vessel, multivessel, and diabetic pa-
tients). We used both intracoronary and intravenous adenosine
and pressure wires from St. Jude Medical and Volcano. FFR
was measured in the standard way (5,6) and used to guide the
clinical case. However, the invasive measurement team was
blinded to the iFR value, which was calculated offline using a
fully automated Matlab algorithm (Mathworks, Inc.).
Calculation of the instantaneous wave-free ratio (iFR).
Wave-intensity analysis was used to identify the backward-
traveling waves (Equation 1). The onset of diastole was
identified from the dicrotic notch, and the diastolic window
was calculated beginning 25% of the way into diastole and
ending 5 ms before the end of diastole. This time was chosen
to reflect the wave-free period in diastole when resistance is
naturally minimized (see Results and Discussion) (Fig. 1).
iFR was calculated as the mean pressure distal to the stenosis
during the diastolic wave-free period (Pd wave-free period) divided
by the mean aortic pressure during the diastolic wave-free
period (Pa wave-free period) (Equation 2). All analyses were
performed in a fully automated manner, eliminating the need
for manual selection of data time points.
Backward-traveling waves ϭ WI _ ϭ Ϫ
1
4pcͩdp
dt
Ϫ pc
du
dt ͪ2
[1]
The wave-free period runs from time (WIϪ[diastole] ϭ 0) to
the end of diastole Ϫ 5 ms.
iFR ϭ
Pd
wave-free period
Pa
wave-free period
[2]
where is the density of blood (taken as 1050 kgϪ3
), c is the
wave speed calculated using the single-point equation (8),
Figure 3 The ADVISE Study Protocol
ADVISE ϭ ADenosine Vasodilator Independent Stenosis Evaluation; FFR ϭ frac-
tional flow reserve; iFR ϭ instantaneous wave-free ratio.
1395JACC Vol. 59, No. 15, 2012 Sen et al.
April 10, 2012:1392–402 Adenosine-Free Measure of Stenosis Severity
5. dP is the incremental change in coronary artery pressure,
and dU is the incremental change in blood velocity.
Data analysis. Processing of digital data (pressure, flow
velocity, electrocardiogram) for the calculation of the vari-
ous indices and intervals discussed (wave-intensity analysis,
coronary resistance, FFR, selection of wave-free diastolic
interval, iFR) was performed at a workstation using Matlab
(Mathworks, Inc.). Statistical analysis was performed using
STATA version 11 (StataCorp, College Station, Texas). A
paired Student t test was used to compare within patients.
The proportional change in resistance during the cardiac
cycle was referenced to the baseline mean resistance. The
relationship between the FFR and iFR for the entire patient
population and all subsequent subgroup analyses was quan-
tified with a Pearson’s product moment correlation coeffi-
cient. Receiver-operating characteristic curves were used to
estimate diagnostic efficiency of iFR and to identify the
most appropriate cutoff value compared with the FFR
treatment threshold of 0.8. Mean values are expressed as
mean Ϯ SD. A repeated-measures analysis was performed
by comparing the iFR from the first half of the recording
with the value from the second half of the recording using
a paired Student t test. The relationship of heart rate and
blood pressure to iFR was quantified with a Pearson product
moment correlation coefficient. A p value Ͻ0.05 was
deemed significant.
Results
Identification of period of stable resistance in the cardiac
cycle. In each of the stenoses included in part 1, intracoro-
nary pressure, flow velocity, and resistance were analyzed
before and during the administration of adenosine (Fig. 2).
Wave-intensity analysis allowed identification of a wave-
free period after the backward decompression wave when
wave intensity and microcirculatory-originating pressure
return to zero (Figs. 1A and 1B). The mean duration of this
period was 354 Ϯ 78 ms (75 Ϯ 6% of diastole), starting 112 Ϯ 26
ms after the onset of diastole. Intracoronary resistance
remained minimized and stable throughout this wave-free
period (Fig. 1C).
Resistance throughout the cardiac cycle at rest and with
pharmacologic vasodilation. Adenosine administration
caused the mean intracoronary resistance over the entire
cardiac cycle to decrease by 51% (613 Ϯ 310 mm Hg s/m vs.
302 Ϯ 315 mm Hg s/m, p Ͻ 0.001). This was predominantly
due to a 75% reduction in the systolic contribution to resistance
(⌬ systolic resistance 461 mm Hg s/m, p Ͻ 0.001) (Fig. 4).
Both the magnitude and variability of intracoronary
resistance identified during the wave-free period were sim-
ilar to those achieved over the entire cardiac cycle during
pharmacologic vasodilation. The magnitude of resistance
during the wave-free period was 284 Ϯ 147 mm Hg s/m
compared with 302 Ϯ 315 mm Hg s/m during pharmaco-
logic vasodilation (p ϭ 0.70) (Fig. 5A). The coefficient of
variation of resistance during the wave-free period was 0.08 Ϯ
0.06 compared with 0.08 Ϯ 0.06 during pharmacologic
vasodilation (p ϭ 0.96) (Fig. 5B).
Reproducibility and diagnostic characteristics of iFR.
The iFR was calculated for each stenosis using the wave-free
time window, as defined previously, and this was compared
with the FFR. The iFR was found to be closely correlated
with the FFR (r ϭ 0.90, y ϭ 1.0x ϩ 0.03) (Fig. 6). Using the
established FFR cutoff threshold of 0.8 to define a positive
result, a receiver-operating characteristic curve was used to
identify the optimal iFR cutoff (0.83) with the greatest diag-
nostic efficiency. The receiver-operating characteristic area
under curve was 93% (Fig. 7). False-negative and false-positive
data for the iFR is demonstrated in Figure 8B; the positive
predictive value of the iFR was 91% and the negative predictive
value was 85%, with a sensitivity and specificity of 85% and
91%, respectively.
Furthermore, the close correlation of iFR with FFR
remained with left coronary (r ϭ 0.90) and right (r ϭ 0.89)
coronary arteries, with a diagnostic accuracy in the right
coronary artery of 91%, consistent with the entire cohort
(Fig. 8). This relationship persisted throughout our sub-
group analysis, with similar levels of correlation indepen-
dent of the type of pressure wire, route of pharmacologic
vasodilator administration, single- or multivessel disease
(Table 2). Furthermore, iFR was found to be independent
of heart rate (range 46 to 120/min; r2
ϭ 0.016), systolic
(r2
ϭ 0.001), and diastolic (r2
ϭ 0.005) pressure. Indeed,
the iFR was also found to be stable in patients with ectopy and
large changes in blood pressure due to respiration (Fig. 9).
Figure 4
Reduction in Systolic Resistance
With Intravenous Adenosine Administration
There was a significant reduction in the systolic component of intracoronary resistance
with adenosine (⌬ systolic resistance: 461 mm Hg s/m, p Ͻ 0.001), which was the
dominant contributor to the mean reduction in resistance during the cardiac
cycle.
1396 Sen et al. JACC Vol. 59, No. 15, 2012
Adenosine-Free Measure of Stenosis Severity April 10, 2012:1392–402
6. Bland-Altman analysis also demonstrates good agree-
ment between measures with a mean difference between the
FFR and iFR of Ϫ0.05 Ϯ 0.19. A repeated-measures
analysis of the iFR was made in 149 stenoses, which
demonstrated a close relationship between the 2 successive
measurements (r ϭ 0.996, p Ͻ 0.001) (Fig. 10), with a
mean difference between iFR measurements of Ϫ0.0005 Ϯ
0.002 (p ϭ 0.78).
Discussion
The main conclusions of this study are that: 1) when
selectively measured within a defined diastolic wave-free
period, resting coronary resistance values are similar to those
observed during adenosine-mediated FFR; and 2) the ratio
Figure 5 Intracoronary Resistance During Pharmacologic Vasodilation Compared With Resistance During the Wave-Free Period
(A) Compared with baseline, there was a significant reduction in resistance with both pharmacologic vasodilation and during the wave-free period. (A, B) There was no
significant difference in the magnitude or variability of resistance with pharmacologic vasodilation (as used for fractional flow reserve) compared with the wave-free period
(as used for instantaneous wave-free ratio). All values are reported as mean Ϯ SE.
Figure 6 Correlation of iFR With FFR
The wave-free period was calculated using a fully automated algorithm. The
instantaneous wave-free ratio (iFR) was calculated by dividing the mean Pd by
Pa during the wave-free period under basal conditions. The iFR was found to
closely agree with the fractional flow reserve (FFR) (r ϭ 0.9, p Ͻ 0.001). The
dotted lines represent the threshold cutoff values for the iFR and FFR.
Figure 7 Diagnostic Characteristics of the iFR
A receiver-operating characteristic curve was calculated using FFR as the refer-
ence gold-standard variable. The threshold cutoff for FFR was taken as 0.80.
The receiver-operating characteristic was found to have an area under the
curve of 93%, suggesting high accuracy of iFR as a diagnostic test. Abbrevia-
tions as in Figure 6.
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7. of distal-to-proximal pressures during this wave-free period
produces an index (iFR) that correlates closely with FFR.
Importance of constant intracoronary resistance in the
functional assessment of stenoses. Coronary blood flow
is unique in that it is determined not only by variations in
pressure arising proximally (as in the aorta and other
systemic arteries) but also concurrent variations arising
distally in the microcirculation (Fig. 11) (8). It is con-
sidered inaccurate to assess the severity of a coronary
stenosis by simply measuring the decrease in mean or
peak pressure across a stenosis under basal conditions
over the entire cardiac cycle because distal coronary
pressure is not simply a residuum of the pressure trans-
mitted from the aortic end of the vessel (Fig. 11A), but is
also due to a pressure component arising from active
compression and decompression of the coronary micro-
Subgroup Analysis: Close Agreement Between the iFR and FFR Across Subgroups AnalyzedTable 2 Subgroup Analysis: Close Agreement Between the iFR and FFR Across Subgroups Analyzed
Stenoses Male Age, yrs Diabetes Hypertension
Adenosine
r ValueIC IV
Single vessel 108 (68.8) 88 (81.5) 57.7 Ϯ 16.3 35 (32.4) 57 (52.8) 74 (68.5) 34 (31.5) 0.89
Multivessel 49 (31.2) 43 (87.8) 66.7 Ϯ 8.7 19 (38.8) 31 (63.3) 20 (40.8) 29 (59.2) 0.92
Coronary artery
LAD 69 (44.0) 59 (83.6) 62.4 Ϯ 10.3 20 (28.4) 43 (61.2) 39 (56.5) 30 (43.5) 0.89
Cx 43 (27.3) 40 (92.7) 63.3 Ϯ 11.3 18 (41.5) 27 (63.4) 21 (48.8) 22 (51.2) 0.91
RCA 45 (28.7) 39 (88.1) 62.2 Ϯ 8.9 19 (42.9) 22 (50.0) 34 (76.2) 11 (23.8) 0.89
Adenosine (route)
Intracoronary 94 (59.9) 77 (80.2) 60.9 Ϯ 9.7 23 (24.0) 49 (51.0) 100 — 0.88
Intravenous 63 (40.1) 54 (88.5) 65.0 Ϯ 10.3 31 (50.8) 39 (63.9) — 100 0.90
Diabetes 54 (34.4) 45 (83.3) 63.5 Ϯ 8.0 54 (100.0) 40 (74.1) 23 (42.6) 31 (57.4) 0.88
Smoker 34 (21.7) 31 (91.1) 57.1 Ϯ 10.1 6 (17.6) 19 (55.9) 8 (23.5) 26 (76.5) 0.85
Hypertension 88 (56.1) 73 (83.0) 64.0 Ϯ 9.8 40 (45.5) 88 (100.0) 49 (55.7) 39 (44.3) 0.92
Values are n (%) or mean Ϯ SD.
IC ϭ intracoronary; IV ϭ intravenous; other abbreviations as in Table 1.
Figure 8 Correlation and Diagnostic Characteristics of the iFR With FFR According to the Coronary Artery
The iFR was found to correlate closely with FFR (r ϭ 0.9). This was consistent in both the right (r ϭ 0.89, red dots) and left (r ϭ 0.90, black dots) coronary arteries (A).
An assessment of false-positive and false-negative results comparing iFR with FFR was then made (B). The treatment categorization of iFR agreed closely with that of
FFR. Specifically, iFR had a diagnostic accuracy, positive predictive value, negative predictive value, sensitivity, and specificity of 88%, 91%, 85%, 85%, and 91%, respec-
tively. This was also independent of the right or left coronary artery. Abbreviations as in Figure 6.
1398 Sen et al. JACC Vol. 59, No. 15, 2012
Adenosine-Free Measure of Stenosis Severity April 10, 2012:1392–402
8. circulation (Fig. 11B). These distal influences cause
dramatic variations in the instantaneous ratio between
pressure and flow (a simple index of intracoronary resis-
tance). Wave-intensity analysis can be used to distinguish
distal microcirculatory-originating influences from prox-
imally originating influences transmitted from the aorta
(8). The most extreme examples of such variations are the
rapid increase in pressure in early systole and the rapid
decrease in early diastole. In early systole, pressure
increases rapidly but flow does not, and so the index of
intracoronary resistance increases rapidly. The rapid in-
crease in pressure without a corresponding increase in
flow is caused by near-perfect matching of compression
waves arising from the aorta and coronary microcircula-
tion during most of systole (8) (Fig. 1A). In early
diastole, the converse happens; pressure decreases while
flow accelerates, and so the index of intracoronary resis-
tance decreases rapidly. This occurs because the micro-
vasculature is suddenly decompressed, causing blood to
be sucked in to the coronary microcirculation (Fig. 1).
After this brief, but rapid, phase of pressure decrease,
pressure and flow then passively decrease together slowly.
During this gradual decline, which extends for the
majority of diastole, the index of coronary resistance is
close to minimal and is stable because there is no further
wave activity arising from either end of the coronary
artery.
Pressure-derived flow indices of coronary stenosis severity
such as FFR depend on the proportional relationship of
pressure to flow, which occurs when resistance is stable (5);
this is only the case for part of the cardiac cycle. Pioneering
scientists seeking clinically applicable methods developed
highly refined approaches to circumvent the computational
limitations of the day by administering pharmacologic
agents such as adenosine (5,9,10). As we demonstrate, these
potent vasodilator agents reduce the dramatic variation in
resistance predominantly by reducing the systolic portion
of resistance (Figs. 4 and 5) to obtain a stable and mini-
mized resistance value.
Recent advances in real-time processing now permit
automatic selection of the diastolic wave-free period, using
measurements of pressure alone, that provides this stable
and minimal resistance value without having to administer
vasodilator agents. During this diastolic wave-free period,
60
120
0 5 10
0
0.5
1.0
75
150
0 5 10 15
0
0.5
1.0
PaandPd
Pressure
(mmHg)
iFR
PaandPd
Pressure
(mmHg)
iFR
0
0
Time (s)
A
B
Figure 9 Stability of the iFR During Hemodynamic Perturbation
The iFR provides a beat-to-beat pressure ratio during the wave-free window, comparing each distal pressure with its corresponding aortic pressure. This ensures accuracy
regardless of arrhythmia (A, ectopy) or variations in blood pressure and heart rate (B, tachycardia and respiratory variation in blood pressure). Abbreviations as in
Figure 6.
1399JACC Vol. 59, No. 15, 2012 Sen et al.
April 10, 2012:1392–402 Adenosine-Free Measure of Stenosis Severity
9. coronary flow is predominantly determined by the passive
pressure gradient between the proximal and distal ends of
the vessel, analogous to water flowing down a pipe. This
natural state of stable and minimized resistance occurs
spontaneously in every cardiac cycle, creating an opportunity
to calculate a pressure-derived index without the need for
pharmacologic intervention.
Identification of the wave-free diastolic window. We
identified in all patients a period in diastole when
resistance is stable. Across all individual patients, the
start of this window was 112 Ϯ 26 ms after the onset of
diastole (25 Ϯ 6% into diastole), and the end was the end
of diastole. For automatic computation, we consider it
practical to use an algorithmic definition of the time
window that begins 25% of the way into diastole (after
the early unwanted variations) and ends 5 ms before the
end of diastole, allowing 75% of diastole during which
pressure measurements can be made.
iFR as a tool for instant diagnosis: the challenge of minor
uncertainty of FFR. Using an all-comers selection criteria
similar to the FAME (Fractional Flow Reserve Versus
Angiography for Multivessel Evaluation) study (6), iFR was
found to agree closely with FFR with a diagnostic efficiency
(area under the curve) of 93%. This was seen consistently
Figure 10 Repeated-Measures Analysis of the iFR and Bland-Altman Plot
The baseline pressure data were split in half, and the iFR for each half was calculated. The correlation of iFR 1with iFR 2 demonstrates high reproducibility across the
entire range of stenosis severity (B, mean difference between measures Ϫ0.0005 Ϯ 0.002, p ϭ 0.78). The Bland-Altman plot demonstrates good agreement between
the iFR and FFR across the entire range of stenosis severity. Abbreviations as in Figure 6.
Figure 11 Schematic Illustrating the Importance of Microcirculatory (or Distal Originating) Pressure in the Coronary Arteries
In all blood vessels, blood flows down a pressure gradient. In the systemic circulation, a pressure wave is generated after a ventricular contraction traveling from the
proximal to distal end of the vessel. Although most of this wave energy travels in an anterograde direction, a small proportion is reflected back at the site of impedance
mismatch from the distal circulation (A). This contrasts with the coronary circulation where a pressure wave is generated at both the proximal and distal ends of the ves-
sel at differing times in the cardiac cycle. Thus, intracoronary pressure distal to a stenosis is a composite of residual proximally originating pressure and the distal origi-
nating pressure from compression of the intramyocardial vessels. The iFR is calculated during the wave-free period in diastole, when distal originating pressure in
minimized (Fig. 1). The size of the arrows pointing in the direction of wave travel denote the contribution of proximal or distal pressure to total pressure, with proximal
pressure predominant in the systemic artery (A) and equal contribution to total pressure from both the proximal and distal ends in the coronary artery (B).
1400 Sen et al. JACC Vol. 59, No. 15, 2012
Adenosine-Free Measure of Stenosis Severity April 10, 2012:1392–402
10. across all subgroups analyzed (multivessel, single vessel,
right and left coronary arteries) and independent of the
method of assessment (intracoronary vs. intravenous aden-
osine or RADI vs. Volcano pressure wire) (Table 1).
FFR is itself known to vary slightly from one measure-
ment to the next, and therefore no technique can correlate
perfectly with it. FFR has a coefficient of variation of 4.8%
(95% confidence interval: 3.5 to 7.4) and a mean difference
between repeated measures of 0.01 Ϯ 0.04 (11). iFR
compares favorably with a very small mean difference
between repeated measures Ϫ0.0005 Ϯ 0.002 (p ϭ 0.78).
Although the variability in FFR is small, that in the iFR
is smaller. We speculate that this occurs for 2 main reasons.
First, spontaneous beat-to-beat fluctuations are most exag-
gerated during systole (included in FFR, but excluded by
definition in iFR). Second, when ectopics or other un-
wanted disturbances occur, the FFR relies on averaging
multiple beats to “dilute” their effects, whereas the iFR
matches proximal and distal pressures on a beat-by-beat
basis by performing a paired comparison between each
“mother” aortic diastolic pressure component and its own
corresponding “daughter” distal diastolic pressure compo-
nent, resulting in more stable values, even during arrhyth-
mia (Fig. 9). Categorization using iFR was found to agree
with categorization using FFR in 88% of cases treating FFR
as the gold standard. However, if the previously discussed,
well-documented intrinsic variability of FFR is accounted
for, the adjusted iFR diagnostic accuracy would increase to
around 95% with positive and negative predictive values of
97% and 93%, respectively (11).
Clinical implications of iFR. FFR has been revolutionary
in implementing intracoronary physiology in clinical prac-
tice. Its success is a reflection of the simplicity of the
technique and accumulation of clinical evidence demon-
strating the safety of adopting an FFR-guided approach to
revascularization (6,10,12,13). FFR is currently recom-
mended as a surrogate for ischemia detection tests in the
catheterization laboratory in clinical practice guidelines (14)
and, compared with angiography guidance, improves pa-
tient outcomes, while decreasing procedural time and costs
when used in percutaneous coronary interventions (6,7).
Despite this, use of the FFR is far from universal, being
performed in only 6% of percutaneous coronary intervention
procedures in the United States (14). The need to admin-
ister adenosine has been highlighted as one of the reasons
for this poor adoption rate (15). There are several reasons
that may explain the reluctance of physicians to use aden-
osine. First, in addition to costs, the clinical effort of
administering adenosine is not trivial, and so it has to be
actively chosen on each occasion. Second, some patients
have contraindications such as asthma, severe chronic ob-
structive pulmonary disease, hypotension, and bradycardia.
Third, most patients find it uncomfortable. Fourth, it may
require central venous access, which might otherwise not be
necessary for the procedure (16). Finally, initial adenosine
response may be incomplete in some patients, and this may
be difficult to predict reliably in advance (17–19). Thus, a
wider use of intracoronary physiology would be expected if
the technique is simplified even further. iFR would circum-
navigate these issues, permitting the benefits of FFR to be
accessible to a wider population at lower cost, with less
patient discomfort and shorter procedural times.
This study’s cohort of patients reflects a wide demo-
graphic spectrum and is similar to that of the FAME study
(6). The results of this study could be followed by further
validation of iFR in a larger cohort to better establish the
diagnostic efficiency of each technique in the same study
population. Although this appears to be a prerequisite
before iFR can be proposed as an alternative to FFR in all
contexts, the excellent reproducibility and agreement in
classification with FFR (within the biological variability of
FFR) suggest that iFR will expand intracoronary functional
assessment to circumstances in which administration of
adenosine is not desirable.
A final word should be dedicated to previous research on
the use of diastolic pressures for FFR calculation, the
so-called diastolic FFR (20,21). The validation of diastolic
FFR demonstrated that diastolic-only pressure measure-
ments can be used to estimate stenosis severity with the
same diagnostic efficiency as FFR, which uses cycle-
averaged pressure measurements (19). This supports the
concept that systolic flow can be neglected in the pressure-
derived indices like diastolic FFR and iFR. The optimal
cutoff value to identify ischemia-generating stenoses in that
study was slightly higher for diastolic FFR (0.76) than for
FFR (0.75) (19), a fact that is in agreement with the
differences found in our study between the (0.83) and the
currently recommended 0.80 FFR cutoff value. However,
major differences between the diastolic FFR and iFR should
be noted: 1) like FFR, diastolic FFR requires the use of
adenosine; and 2) measurements were obtained throughout
diastole and not selectively at a specific wave-free interval.
As discussed previously, the use of this wave-free period by
iFR, when coronary resistance remains unchanged and
minimal, provides a measure that closely correlates with
FFR.
Study limitations. There is no gold-standard ischemia
test. We chose FFR because it is quantitative and specific
to a vessel, has been validated against 3 noninvasive tests,
has robust long-term clinical outcome data, and is the
investigation recommended by cardiology guidelines for
the assessment of intermediate stenoses in the cardiac
catheter laboratory. However, there remains a possibility
that any disagreement between the 2 indices may reflect
the diagnostic accuracy of FFR rather than iFR.
This pilot study suggests that an iFR value of 0.83
provides optimal agreement with an FFR of 0.8. Several
hypotheses can be put forward to explain this difference in
optimal cutoff values. First, since the optimal cutoff value for
diastolic FFR, a diastolic-only pressure–derived method
such as the iFR, is also slightly higher than that of FFR
(19), it is possible that this difference may be genuinely due
1401JACC Vol. 59, No. 15, 2012 Sen et al.
April 10, 2012:1392–402 Adenosine-Free Measure of Stenosis Severity
11. to differences in how the indices are calculated. Second, it
may result from subtle differences between pharmacologic
stabilization of resistance compared with that that occurs
naturally in the wave-free period. Finally, the possibility that
it may be artifactual, given the relatively small size of our
study, cannot be ruled out. With a larger patient population,
any differences might be further explored, and this cutoff
value may change in a manner similar to that of FFR during
its development. Therefore, future studies are needed to
address the diagnostic accuracy between FFR and iFR and
the best cutoff value for iFR.
Intracoronary and intravenous administration of adeno-
sine can have differing effects on peripheral and coronary
arterial circulations. To mitigate potential confounding
from either of these administration routes, we decided to
include both intravenous and intracoronary administration
in our study. In subanalyses of our results, we found no
significant differences between either routes of administra-
tion (Table 2). Finally, a similar agreement between iFR
and FFR values was documented in the right and left
coronary artery despite the more predominant systolic com-
ponent of flow in the right coronary artery.
Conclusions
The existence of a wave-free period in diastole when
coronary resistance is constant and minimal opens the
possibility of performing pressure-derived stenosis assessment
without the need for pharmacologic vasodilation. iFR, a new
index based on this principle, has an excellent diagnostic
efficiency in identifying stenoses with an FFR Ͻ0.80 and could
be used for intracoronary functional assessment when admin-
istration of adenosine is not desirable.
Acknowledgments
The authors acknowledge the support of the NIHR Bio-
medical Research Centre funding scheme and Helen Davies
for mathematical assistance.
Reprint requests and correspondence: Dr. Sayan Sen, Interna-
tional Centre of Circulatory Health, National Heart and Lung
Institute, 59-61 North Wharf Road, London W2 1LA, United
Kingdom. E-mail: sayan.sen@imperial.ac.uk.
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Key Words: adenosine y coronary stenosis y fractional flow reserve y
revascularization.
1402 Sen et al. JACC Vol. 59, No. 15, 2012
Adenosine-Free Measure of Stenosis Severity April 10, 2012:1392–402