Tiffany Patterson

Transcatheter Aortic Valve Implantation for Pure Severe Native Aortic Valve Regurgitation

OBJECTIVES This study sought to collect data and evaluate the anecdotal use of transcatheter aortic valve implantation (TAVI) in pure native aortic valve regurgitation (NAVR) for patients who were deemed surgically inoperable BACKGROUND Data and experience with TAVI in the treatment of patients with pure severe NAVR are limited. METHODS Data on baseline patient characteristics, device and procedure parameters, echocardiographic parameters, and outcomes up to July 2012 were collected retrospectively from 14 centers that have performed TAVI for NAVR. RESULTS A total of 43 patients underwent TAVI with the CoreValve prosthesis (Medtronic, Minneapolis, Minnesota) at 14 centers (mean age, 75.3 ± 8.8 years; 53% female; mean logistic EuroSCORE (European System for Cardiac Operative Risk Evaluation), 26.9 ± 17.9%; and mean Society of Thoracic Surgeons score, 10.2 ± 5.3%). All patients had severe NAVR on echocardiography without aortic stenosis and 17 patients (39.5%) had the degree of aortic valvular calcification documented on CT or echocardiography. Vascular access was transfemoral (n = 35), subclavian (n = 4), direct aortic (n = 3), and carotid (n = 1). Implantation of a TAVI was performed in 42 patients (97.7%), and 8 patients (18.6%) required a second valve during the index procedure for residual aortic regurgitation. In all patients requiring second valves, valvular calcification was absent (p = 0.014). Post-procedure aortic regurgitation grade I or lower was present in 34 patients (79.1%). At 30 days, the major stroke incidence was 4.7%, and the all-cause mortality rate was 9.3%. At 12 months, the all-cause mortality rate was 21.4% (6 of 28 patients). CONCLUSIONS This registry analysis demonstrates the feasibility and potential procedure difficulties when using TAVI for severe NAVR. Acceptable results may be achieved in carefully selected patients who are deemed too high risk for conventional surgery, but the possibility of requiring 2 valves and leaving residual aortic regurgitation remain important considerations.

Optical coherence tomography: from research to practice

Optical coherence tomography (OCT) is a high-resolution imaging technique with great versatility of applications. In cardiology, OCT has remained hitherto as a research tool for characterization of vulnerable plaques and evaluation of neointimal healing after stenting. However, OCT is now successfully applied in different clinical scenarios, and the introduction of frequency domain analysis simplified its application to the point it can be considered a potential alternative to intravascular ultrasound for clinical decision-making in some cases. This article reviews the use of OCT for assessment of lesion severity, characterization of acute coronary syndromes, guidance of intracoronary stenting, and evaluation of long-term results.

A Unravelling the Mechanisms of Exercise Induced Ischaemia, its Optimal Assessment, and Alleviation with Nitroglycerine

Introduction The mechanisms governing exercise-induced angina, its alleviation by the most common anti-anginal drug, nitroglycerine (GTN), and the best techniques to elucidate whether a stenosis causes sufficient ischaemia to warrant revascularisation are incompletely understood. In this multifaceted investigation we aimed to investigate these processes. Methods A porcine model of coronary stenosis was developed for invasive assessment of coronary haemodynamics and perfusion MRI. Coronary lesions were created using an external balloon constrictor to investigate the optimal method of assessing stenosis severity, using an invasive standard for coronary ischaemia of Hyperemic Stenosis Resistance (HSR) and a non-invasive standard of adenosine stress perfusion cardiac MRI. In the human translation, 21 Patients with exertional angina and documented coronary artery disease underwent cardiac catheterisation via radial access and performed incremental exercise using a supine cycle ergometer. As they developed limiting angina, sublingual GTN was administered and exercise continued for two minutes at the same workload. Throughout exercise, distal coronary pressure and flow velocity, and central aortic pressure were recorded using sensor wires. After a period of rest, intravenous adenosine was administered to assess lesion severity using conventional catheter methods. Results 64 lesions of varying severity were created in the porcine model showing that Fractional Flow Reserve (FFR) provided the best test of stenosis severity, which was significantly better than instantaneous wave-free ratio (iFR), Basal Stenosis Resistance (BSR), and resting Pd/Pa ratio. In the human translation, indices measured at peak exercise (HSR, FFR) performed significantly better than adenosine-based indices, which were superior to measurements at rest. Compared to peak exercise, patients continued to exercise post-GTN administration with less ischemia (P = 0.003). Coronary pressure and flow were maintained (P=NS), in the face of significant reduction in left ventricular afterload (0.01). On wave intensity analysis, significant increases were seen in both the energy of the diastolic microcirculatory backward expansion wave, and the systolic backward compression wave related to myocardial contractility (0.05). Conclusions Coronary ischaemia can be studied using a porcine model in the catheter laboratory as well as MRI environment. This model showed that the adenosine based indices, HSR and FFR, performed significantly better than those measured at rest, suggesting that these should be used in the assessment of lesion severity. The human exercise protocol provides a new paradigm with which the physiology of ischemia as well as the performance of novel and established anti-anginals can be studied. Administration of GTN causes harmonious changes in the systemic and coronary circulation that combine to reduce afterload while maintaining coronary perfusion. The study also demonstrates, for the first time, a coronary derived index with potential to measure myocardial contractility.

Response by Asrress et al to Letter Regarding Article, “Physiology of Angina and Its Alleviation With Nitroglycerin: Insights From Invasive Catheter Laboratory Measurements During Exercise”

We are grateful to Jin-shan and Xue-bin for their interest in our work, where we described the physiology of angina and its alleviation with nitroglycerin during physiological exercise in the catheter laboratory while simultaneously measuring intracoronary and aortic hemodynamics.1 It was also the subject of an insightful editorial.2 We agree entirely that understanding the physiological mechanisms by which other commonly used drugs alleviate angina is …

Physiology of Angina and Its Alleviation With NitroglycerinClinical Perspective: Insights From Invasive Catheter Laboratory Measurements During Exercise

Background: The mechanisms governing exercise-induced angina and its alleviation by the most commonly used antianginal drug, nitroglycerin, are incompletely understood. The purpose of this study was to develop a method by which the effects of antianginal drugs could be evaluated invasively during physiological exercise to gain further understanding of the clinical impact of angina and nitroglycerin. Methods: Forty patients (mean age, 65.2±7.6 years) with exertional angina and coronary artery disease underwent cardiac catheterization via radial access and performed incremental exercise using a supine cycle ergometer. As they developed limiting angina, sublingual nitroglycerin was administered to half the patients, and all patients continued to exercise for 2 minutes at the same workload. Throughout exercise, distal coronary pressure and flow velocity and central aortic pressure were recorded with sensor wires. Results: Patients continued to exercise after nitroglycerin administration with less ST-segment depression (P=0.003) and therefore myocardial ischemia. Significant reductions in afterload (aortic pressure, P=0.030) and myocardial oxygen demand were seen (tension-time index, P=0.024; rate-pressure product, P=0.046), as well as an increase in myocardial oxygen supply (Buckberg index, P=0.017). Exercise reduced peripheral arterial wave reflection (P<0.05), which was not further augmented by the administration of nitroglycerin (P=0.648). The observed increases in coronary pressure gradient, stenosis resistance, and flow velocity did not reach statistical significance; however, the diastolic velocity–pressure gradient relation was consistent with a significant increase in relative stenosis severity (k coefficient, P<0.0001), in keeping with exercise-induced vasoconstriction of stenosed epicardial segments and dilatation of normal segments, with trends toward reversal with nitroglycerin. Conclusions: The catheterization laboratory protocol provides a model to study myocardial ischemia and the actions of novel and established antianginal drugs. Administration of nitroglycerin causes changes in the systemic and coronary circulation that combine to reduce myocardial oxygen demand and to increase supply, thereby attenuating exercise-induced ischemia. Designing antianginal therapies that exploit these mechanisms may provide new therapeutic strategies.

Physiology of Angina and Its Alleviation With Nitroglycerin

Background: The mechanisms governing exercise-induced angina and its alleviation by the most commonly used antianginal drug, nitroglycerin, are incompletely understood. The purpose of this study was to develop a method by which the effects of antianginal drugs could be evaluated invasively during physiological exercise to gain further understanding of the clinical impact of angina and nitroglycerin. Methods: Forty patients (mean age, 65.2±7.6 years) with exertional angina and coronary artery disease underwent cardiac catheterization via radial access and performed incremental exercise using a supine cycle ergometer. As they developed limiting angina, sublingual nitroglycerin was administered to half the patients, and all patients continued to exercise for 2 minutes at the same workload. Throughout exercise, distal coronary pressure and flow velocity and central aortic pressure were recorded with sensor wires. Results: Patients continued to exercise after nitroglycerin administration with less ST-segment depression (P=0.003) and therefore myocardial ischemia. Significant reductions in afterload (aortic pressure, P=0.030) and myocardial oxygen demand were seen (tension-time index, P=0.024; rate-pressure product, P=0.046), as well as an increase in myocardial oxygen supply (Buckberg index, P=0.017). Exercise reduced peripheral arterial wave reflection (P<0.05), which was not further augmented by the administration of nitroglycerin (P=0.648). The observed increases in coronary pressure gradient, stenosis resistance, and flow velocity did not reach statistical significance; however, the diastolic velocity–pressure gradient relation was consistent with a significant increase in relative stenosis severity (k coefficient, P<0.0001), in keeping with exercise-induced vasoconstriction of stenosed epicardial segments and dilatation of normal segments, with trends toward reversal with nitroglycerin. Conclusions: The catheterization laboratory protocol provides a model to study myocardial ischemia and the actions of novel and established antianginal drugs. Administration of nitroglycerin causes changes in the systemic and coronary circulation that combine to reduce myocardial oxygen demand and to increase supply, thereby attenuating exercise-induced ischemia. Designing antianginal therapies that exploit these mechanisms may provide new therapeutic strategies.

Use of novel intracoronary technology to investigate the effect of cold air inhalation during exercise on coronary microvascular resistance and blood flow in coronary artery disease: a cross-sectional study

Abstract Background Highest rates of exertion-related cardiac death occur during cold air inhalation (eg, shovelling snow), but the pathophysiological changes are unclear. Novel technology with intracoronary wires simultaneously and accurately measures coronary artery pressure and coronary blood flow, allowing physiological investigation of the effects of cold air during exercise. We explored the effects of exercise with and without cold air on coronary microvascular resistance and coronary blood flow in patients with coronary artery disease. Methods Patients with severe coronary artery stenoses undergoing coronary angiography were allocated to 5 min of cold air inhalation (–15°C), exercise (incremental supine ergometry), or exercise with cold air. We used two-way ANOVA to compare rest and peak measurements of coronary blood flow and microvascular resistance. We also used wave intensity analysis to identify waves that accelerate and decelerate coronary blood flow, and calculated the proportional contribution of accelerating waves as a coronary perfusion efficiency index. Findings We recruited 39 patients (mean 62 years [SD 9]), obtaining 51 datasets (14 cold air alone, 24 exercise, 13 exercise with cold air). 12 patients were in both the exercise and exercise with cold air groups, and for these patients the order was randomised. Microvascular resistance increased during cold air alone (558 mm Hg/cm per s [133] at rest vs 655 [221] at peak, p=0·04), and decreased during exercise (579 [192] vs 431 [166], p vs 495 [150]). The increase in coronary blood flow was similarly 34% less during exercise with cold air (19·3 cm/s [7·4] at rest vs 26·0 [10·7] at peak, p=0·04) than without (18·8 [7·3] vs 28·4 [11·3], p=0·04). An increase in coronary perfusion efficiency during exercise (69·8% [12·0] at rest vs 77·7 [9·2] at peak, p=0·05) was abolished with the addition of cold air during exercise (70·3 [10·7] vs 69·3 [10·0]). Interpretation We provide the first evidence, to our knowledge, that cold air substantially attenuates the reduction in microvascular resistance and the increase in coronary blood flow that normally occur during exercise. Moreover, although the heart has improved coronary perfusion efficiency during exercise, it can be reduced when combined with cold air. This finding suggests that cold air during exercise can impede coronary vasodilatation and ventricular relaxation, rendering the heart more susceptible to ischaemia. Funding British Heart Foundation, National Institute for Health Research.

Primary Angioplasty For Patients in Cardiogenic Shock: Optimal Management

Cardiogenic shock complicates approximately 5-10 % of all MI events and remains the most common cause of death among MI cases. Over the past few decades, the mortality rate associated with cardiogenic shock has decreased with the introduction of early revascularisation, although there are limited data for patients with triple-vessel disease and left main stem disease. In more recent years, there have been a number of advances in the mechanical circulatory support devices that can help improve the haemodynamics of patients in cardiogenic shock. Despite these advances, together with progress in the use of inotropes and vasopressors, cardiogenic shock remains associated with high morbidity and mortality rates. This review will outline the management of cardiogenic shock complicating acute MI with a smajor focus on revascularisation techniques and the use of mechanical circulatory support devices.

31 Unravelling the Mechanisms of Mental Stress Induced Myocardial Ischaemia

Background Mental stress triggers myocardial ischaemia at cardiac workloads that are lower than those that cause exercise-induced ischaemia in the same patient. Clinical relevance is highlighted by observational studies demonstrating marked increases in cardiovascular events when large populations are exposed to acute mental stress for example by earthquakes and publicised national sports events. In contrast, even in patients with known coronary artery disease and exertional angina, exercise is safe and beneficial. These differences may reflect underlying pathophysiology with vascular dysregulation limiting myocardial blood flow during mental stress. Methods Simultaneous intracoronary pressure and flow velocity data were acquired in a target artery from 15 patients with significant coronary artery disease (FFR >0.8 and or stenosis >70%) and 11 controls following exposure to mental stress during cardiac catheterisation. Oral nitrate preparations, calcium channel antagonists and beta-blockers were stopped 24–48 h in advance. All data were acquired at rest and at peak mental stress. Mental stress involved a 6-minute mental stress test consisting of mental arithmetic and the Stroop test. Coronary flow average peak velocity (APV), microvascular resistance (MVR) and buckberg index (BI; a surrogate of subendocardial ischaemia) were calculated. Wave intensity analysis also differentiated waves that accelerate and decelerate coronary flow Results Mental stress was associated with an increase in systolic blood pressure (SBP, 28.43 mmHg; p = 0<0001), diastolic blood pressure (DBP, 14.47 mmHg; p = 0<0001), and heart rate (HR, 13.63 bpm; p = 0<0001). Rate pressure product (RPP) a marker of myocardial oxygen demand increased by 4429 (p = 0<0001). In patients with coronary disease this increase in demand was not met by an increase in coronary flow but instead by a paradoxical increase in microvascular resistance (206.1; p = 0.0096), resulting in subendocardial ischaemia as reflected by a fall in the BI (-0.23 (p < 0.0001). In contrast, an increase in coronary flow was observed in response to mental stress in the control group (5.25; p = 0.003). This increase in coronary flow was a result of an increase in the backward expansion wave and forward compression wave reflecting an increase in sympathetic activity and myocardial contractility.Abstract 31 Figure 1 Conclusions Exposure to mental stress is associated with an increase in myocardial work and oxygen demand that is met by an increase in coronary flow in patients with unobstructed coronaries. Paradoxical microvascular dysfunction in response to mental stress does occur and this abnormal endothelial response appears to correlate with the extent of atherosclerosis in the vessel. This likely plays a key role in the mechanism of mental stress induced myocardial ischaemia and provides an exciting target for future therapies.

6 Unravelling the mechanisms of mental stress vs exercise induced myocardial ischaemia

Background Mental stress (MS) triggers myocardial ischaemia at cardiac workloads that are lower than those that cause exercise-induced ischaemia in the same patient. Methods Intracoronary pressure and flow velocity data were acquired from 15 CAD (FFR <0.8 and/or >70% stenosis) patients and 11 controls during MS (mental arithmetic, stroop test). 7 CAD patients and 5 controls also underwent cycle ergometer exercise stress (ES). Coronary flow average peak velocity (APV), microvascular resistance (MR) and Buckberg index (BI) were calculated. Results At peak MS rate pressure product (RPP), a marker of myocardial oxygen demand, increased by 4418 ± 2353mmHg.bpm (p = 0 <0001). Despite this there was no increase in coronary flow but instead a paradoxical rise in MR (p = 0.01) and a fall in the BI (p < 0.001), a surrogate for subendocardial ischaemia. Interestingly wave free MR, more reflective of vascular tone and less affected by the contractile forces of the ventricle, did not increase during RPP matched ES (see Figure 1). In contrast an increase in coronary flow predominantly driven by the forward compression and backward expansion waves was observed in the control group (p = 0.001). Conclusion A paradoxical rise in MR does occur in response to MS that is not seen with ES at similar workloads. This abnormal endothelial response correlates with the extent of atherosclerosis in the vessel. Abstract 6 Figure 1 Coronary flow and microvascular resistance in response to mental and exercise stress