ChaMP-CMD: A Phenotype-Blinded, Randomized Controlled, Cross-Over Trial.

BACKGROUND: Angina with nonobstructive coronary arteries is a common condition for which no effective treatment has been established. We hypothesized that the measurement of coronary flow reserve (CFR) allows identification of patients with angina with nonobstructive coronary arteries who would benefit from anti-ischemic therapy. METHODS: Patients with angina with nonobstructive coronary arteries underwent blinded invasive CFR measurement and were randomly assigned to receive 4 weeks of amlodipine or ranolazine. After a 1-week washout, they crossed over to the other drug for 4 weeks; final assessment was after the cessation of study medication for another 4 weeks. The primary outcome was change in treadmill exercise time, and the secondary outcome was change in Seattle Angina Questionnaire summary score in response to anti-ischemic therapy. Analysis was on a per protocol basis according to the following classification: coronary microvascular disease (CMD group) if CFR<2.5 and reference group if CFR≥2.5. The study protocol was registered before the first patient was enrolled (International Standard Randomised Controlled Trial Number: ISRCTN94728379). RESULTS: Eighty-seven patients (61±8 years of age; 62% women) underwent random assignment (57 CMD group and 30 reference group). Baseline exercise time and Seattle Angina Questionnaire summary scores were similar between groups. The CMD group had a greater increment (delta) in exercise time than the reference group in response to both amlodipine (difference in delta, 82 s [95% CI, 37-126 s]; P<0.001) and ranolazine (difference in delta, 68 s [95% CI, 21-115 s]; P=0.005). The CMD group reported a greater increment (delta) in Seattle Angina Questionnaire summary score than the reference group in response to ranolazine (difference in delta, 7 points [95% CI, 0-15]; P=0.048), but not to amlodipine (difference in delta, 2 points [95% CI, -5 to 8]; P=0.549). CONCLUSIONS: Among phenotypically similar patients with angina with nonobstructive coronary arteries, only those with an impaired CFR derive benefit from anti-ischemic therapy. These findings support measurement of CFR to diagnose and guide management of this otherwise heterogeneous patient group.

Post-infarction ventricular septal defect: percutaneous or surgical management in the UK national registry.

AIMS: Post-infarction ventricular septal defect (PIVSD) is a mechanical complication of acute myocardial infarction (AMI) with a poor prognosis. Surgical repair is the mainstay of treatment, although percutaneous closure is increasingly undertaken. METHODS AND RESUTS: Patients treated with surgical or percutaneous repair of PIVSD (2010-2021) were identified at 16 UK centres. Case note review was undertaken. The primary outcome was long-term mortality. Patient groups were allocated based upon initial management (percutaneous or surgical). Three-hundred sixty-two patients received 416 procedures (131 percutaneous, 231 surgery). 16.1% of percutaneous patients subsequently had surgery. 7.8% of surgical patients subsequently had percutaneous treatment. Times from AMI to treatment were similar [percutaneous 9 (6-14) vs. surgical 9 (4-22) days, P = 0.18]. Surgical patients were more likely to have cardiogenic shock (62.8% vs. 51.9%, P = 0.044). Percutaneous patients were substantially older [72 (64-77) vs. 67 (61-73) years, P < 0.001] and more likely to be discussed in a heart team setting. There was no difference in long-term mortality between patients (61.1% vs. 53.7%, P = 0.17). In-hospital mortality was lower in the surgical group (55.0% vs. 44.2%, P = 0.048) with no difference in mortality after hospital discharge (P = 0.65). Cardiogenic shock [adjusted hazard ratio (aHR) 1.97 (95% confidence interval 1.37-2.84), P < 0.001), percutaneous approach [aHR 1.44 (1.01-2.05), P = 0.042], and number of vessels with coronary artery disease [aHR 1.22 (1.01-1.47), P = 0.043] were independently associated with long-term mortality. CONCLUSION: Surgical and percutaneous repair are viable options for management of PIVSD. There was no difference in post-discharge long-term mortality between patients, although in-hospital mortality was lower for surgery.

Coronary Microvascular Dysfunction Is Associated With Myocardial Ischemia and Abnormal Coronary Perfusion During Exercise.

BACKGROUND: Coronary microvascular dysfunction (MVD) is defined by impaired flow augmentation in response to a pharmacological vasodilator in the presence of nonobstructive coronary artery disease. It is unknown whether diminished coronary vasodilator response correlates with abnormal exercise physiology or inducible myocardial ischemia. METHODS: Patients with angina and nonobstructive coronary artery disease had simultaneous coronary pressure and flow velocity measured using a dual sensor-tipped guidewire during rest, supine bicycle exercise, and adenosine-mediated hyperemia. Microvascular resistance (MR) was calculated as coronary pressure divided by flow velocity. Wave intensity analysis quantified the proportion of accelerating wave energy (perfusion efficiency). Global myocardial blood flow and subendocardial:subepicardial perfusion ratio were quantified using 3-Tesla cardiac magnetic resonance imaging during hyperemia and rest; inducible ischemia was defined as hyperemic subendocardial:subepicardial perfusion ratio <1.0. Patients were classified as having MVD if coronary flow reserve <2.5 and controls if coronary flow reserve ≥2.5, with researchers blinded to the classification. RESULTS: Eighty-five patients were enrolled (78% female, 57±10 years), 45 (53%) were classified as having MVD. Of the MVD group, 82% had inducible ischemia compared with 22% of controls (P<0.001); global myocardial perfusion reserve was 2.01±0.41 and 2.68±0.49 (P<0.001). In controls, coronary perfusion efficiency improved from rest to exercise and was unchanged during hyperemia (59±11% vs 65±14% vs 57±18%; P=0.02 and P=0.14). In contrast, perfusion efficiency decreased during both forms of stress in MVD (61±12 vs 44±10 vs 42±11%; both P<0.001). Among patients with a coronary flow reserve <2.5, 62% had functional MVD, with normal minimal MR (hyperemic MR<2.5 mmHg/cm/s), and 38% had structural MVD with elevated hyperemic MR. Resting MR was lower in those with functional MVD (4.2±1.0 mmHg/cm/s) than in those with structural MVD (6.9±1.7 mmHg/cm/s) or controls (7.3±2.2 mmHg/cm/s; both P<0.001). During exercise, the structural group had a higher systolic blood pressure (188±25 mmHg) than did those with functional MVD (161±27 mmHg; P=0.004) and controls (156±30 mmHg; P<0.001). Functional and structural MVD had similar stress myocardial perfusion and exercise perfusion efficiency values. CONCLUSION: In patients with angina and nonobstructive coronary artery disease, diminished coronary flow reserve characterizes a cohort with inducible ischemia and a maladaptive physiological response to exercise. We have identified 2 endotypes of MVD with distinctive systemic vascular responses to exercise; whether endotypes have a different prognosis or require different treatments merits further investigation.

Physiology of Angina and Its Alleviation With Nitroglycerin: 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.

Noninvasive calculation of the aortic blood pressure waveform from the flow velocity waveform: a proof of concept.

Estimation of aortic and left ventricular (LV) pressure usually requires measurements that are difficult to acquire during the imaging required to obtain concurrent LV dimensions essential for determination of LV mechanical properties. We describe a novel method for deriving aortic pressure from the aortic flow velocity. The target pressure waveform is divided into an early systolic upstroke, determined by the water hammer equation, and a diastolic decay equal to that in the peripheral arterial tree, interposed by a late systolic portion described by a second-order polynomial constrained by conditions of continuity and conservation of mean arterial pressure. Pulse wave velocity (PWV, which can be obtained through imaging), mean arterial pressure, diastolic pressure, and diastolic decay are required inputs for the algorithm. The algorithm was tested using 1) pressure data derived theoretically from prespecified flow waveforms and properties of the arterial tree using a single-tube 1-D model of the arterial tree, and 2) experimental data acquired from a pressure/Doppler flow velocity transducer placed in the ascending aorta in 18 patients (mean ± SD: age 63 ± 11 yr, aortic BP 136 ± 23/73 ± 13 mmHg) at the time of cardiac catheterization. For experimental data, PWV was calculated from measured pressures/flows, and mean and diastolic pressures and diastolic decay were taken from measured pressure (i.e., were assumed to be known). Pressure reconstructed from measured flow agreed well with theoretical pressure: mean ± SD root mean square (RMS) error 0.7 ± 0.1 mmHg. Similarly, for experimental data, pressure reconstructed from measured flow agreed well with measured pressure (mean RMS error 2.4 ± 1.0 mmHg). First systolic shoulder and systolic peak pressures were also accurately rendered (mean ± SD difference 1.4 ± 2.0 mmHg for peak systolic pressure). This is the first noninvasive derivation of aortic pressure based on fluid dynamics (flow and wave speed) in the aorta itself.

Wave speed in human coronary arteries is not influenced by microvascular vasodilation: implications for wave intensity analysis.

Wave intensity analysis and wave separation are powerful tools for interrogating coronary, myocardial and microvascular physiology. Wave speed is integral to these calculations and is usually estimated by the single-point technique (SPc), a feasible but as yet unvalidated approach in coronary vessels. We aimed to directly measure wave speed in human coronary arteries and assess the impact of adenosine and nitrate administration. In 14 patients, the transit time Δt between two pressure signals was measured in angiographically normal coronary arteries using a microcatheter equipped with two high-fidelity pressure sensors located Δs = 5 cm apart. Simultaneously, intracoronary pressure and flow velocity were measured with a dual-sensor wire to derive SPc. Actual wave speed was calculated as DNc = Δs/Δt. Hemodynamic signals were recorded at baseline and during adenosine-induced hyperemia, before and after nitroglycerin administration. The energy of separated wave intensity components was assessed using SPc and DNc. At baseline, DNc equaled SPc (15.9 ± 1.8 vs. 16.6 ± 1.5 m/s). Adenosine-induced hyperemia lowered SPc by 40 % (p < 0.005), while DNc remained unchanged, leading to marked differences in respective separated wave energies. Nitroglycerin did not affect DNc, whereas SPc transiently fell to 12.0 ± 1.2 m/s (p < 0.02). Human coronary wave speed is reliably estimated by SPc under resting conditions but not during adenosine-induced vasodilation. Since coronary wave speed is unaffected by microvascular dilation, the SPc estimate at rest can serve as surrogate for separating wave intensity signals obtained during hyperemia, thus greatly extending the scope of WIA to study coronary physiology in humans.

Left Atrial Appendage Occlusion: British Cardiovascular Intervention Society and British Heart Rhythm Society Position Statement.

Percutaneous left atrial appendage occlusion aims to reduce the risk of stroke in patients with AF, particularly those who are not good candidates for systemic anticoagulation. The procedure has been studied in large international randomised trials and registries and was approved by the National Institute for Health and Care Excellence in 2014 and by NHS England in 2018. This position statement summarises the evidence for left atrial appendage occlusion and presents the current indications. The options and consensus on best practice for pre-procedure planning, undertaking a safe and effective implant and appropriate post-procedure management and follow-up are described. Standards regarding procedure volume for implant centres and physicians, the role of multidisciplinary teams and audits are highlighted.

Left Atrial Appendage Occlusion: British Cardiovascular Intervention Society and British Heart Rhythm Society Position Statement.

Percutaneous left atrial appendage occlusion aims to reduce the risk of stroke in patients with AF, particularly those who are not good candidates for systemic anticoagulation. The procedure has been studied in large international randomised trials and registries and was approved by the National Institute for Health and Care Excellence in 2014 and by NHS England in 2018. This position statement summarises the evidence for left atrial appendage occlusion and presents the current indications. The options and consensus on best practice for pre-procedure planning, undertaking a safe and effective implant and appropriate post-procedure management and follow-up are described. Standards regarding procedure volume for implant centres and physicians, the role of multidisciplinary teams and audits are highlighted.

Embolization of percutaneous left atrial appendage closure devices: Timing, management and clinical outcomes.

BACKGROUND: Left atrial appendage (LAA) occluder embolization is an infrequent but serious complication. OBJECTIVES: We aim to describe timing, management and clinical outcomes of device embolization in a multi-center registry. METHODS: Patient characteristics, imaging findings and procedure and follow-up data were collected retrospectively. Device embolizations were categorized according to 1) timing 2) management and 3) clinical outcomes. RESULTS: Sixty-seven centers contributed data. Device embolization occurred in 108 patients. In 70.4 % of cases, it happened within the first 24 h of the procedure. The device was purposefully left in the LA and the aorta in two (1.9 %) patients, an initial percutaneous retrieval was attempted in 81 (75.0 %) and surgery without prior percutaneous retrieval attempt was performed in 23 (21.3 %) patients. Two patients died before a retrieval attempt could be made. In 28/81 (34.6 %) patients with an initial percutaneous retrieval attempt a second, additional attempt was performed, which was associated with a high mortality (death in patients with one attempt: 2.9 % vs. second attempt: 21.4 %, p < 0.001). The primary outcome (bailout surgery, cardiogenic shock, stroke, TIA, and/or death) occurred in 47 (43.5 %) patients. Other major complications related to device embolization occurred in 21 (19.4 %) patients. CONCLUSIONS: The majority of device embolizations after LAA closure occurs early. A percutaneous approach is often the preferred method for a first rescue attempt. Major adverse event rates, including death, are high particularly if the first retrieval attempt was unsuccessful. CONDENSED ABSTRACT: This dedicated multicenter registry examined timing, management, and clinical outcome of device embolization. Early embolization (70.4 %) was most frequent. As a first rescue attempt, percutaneous retrieval was preferred in 75.0 %, followed by surgical removal (21.3 %). In patients with a second retrieval attempt a higher mortality (death first attempt: 2.9 % vs. death second attempt: 24.1 %, p < 0.001) was observed. Mortality (10.2 %) and the major complication rate after device embolization were high.

Endothelial function does not relate to haemoglobin or serum erythropoietin concentrations and these do not explain the gender difference in endothelial function in healthy middle-aged men and women.

BACKGROUND: Haemoglobin scavenges nitric oxide, and a previous study has shown a negative association between flow-mediated vasodilation (FMD), a measure of nitric oxide (NO)-dependent vasomotor function and haemoglobin concentrations [Hb]. Circulating erythropoietin (EPO) is also negatively associated with [Hb] and could influence availability of NO. The purpose of this study was to examine the association of FMD with [Hb] and EPO concentrations and to determine whether these contribute to the sex difference in FMD. FMD (by high-resolution ultrasound), [Hb], circulating immunoreactive EPO and cardiovascular risk factors were measured in 317 healthy middle-aged men and women (183 women, 33 premenopausal, mean age ± SD, 55 ± 6·8 years) participating in a dietary study. RESULTS: In the whole mixed-sex group, FMD was negatively correlated with [Hb] (R = -0·23, P < 0·001). However, in a multivariable model, incorporating sex and other confounding factors, FMD was independently negatively correlated only with age, male sex and systolic blood pressure: standardized regression coefficients -0·21 (P < 0·01), -0·17 (P < 0·05) and -0·20 (P < 0·05) respectively and not with [Hb]. Similarly, when the analysis was restricted to men or to postmenopausal women, there was no significant relationship between FMD and Hb. There was no significant correlation between FMD and EPO on either univariate analysis in the whole group, in each sex, or in multivariate analysis. CONCLUSION: These results suggest that in healthy middle-aged subjects, FMD is not influenced by [Hb] or EPO and these do not contribute to the gender difference in FMD.

Erythropoietin: a future therapy for failing hearts?

Recently, it has been suggested that erythropoietin may be useful in the treatment of cardiovascular disease, particularly heart failure. This may be by improving microvascular blood supply and ventricular function through prevention of apoptosis and angiogenesis. Promising results were seen in animals but the few, limited clinical trials have shown modest benefits. Additionally, concerns exist regarding potential serious adverse effects of erythropoietin. Our current understanding of the non-haematopoietic mechanisms of erythropoietin is presented here, with a review of trials to date, and a discussion of the questions that remain over the use of this drug in heart failure.

Darbepoetin enhances endothelium-dependent vasomotor function in patients with stable coronary artery disease only after preceding ischaemia/reperfusion.

Vasoprotective effects of erythropoietin in animal models are mediated by endothelium-derived NO and/or mobilization of EPCs (endothelial progenitor cells) and may be enhanced by ischaemia: whether they are present in humans is unknown. We examined whether the erythropoietin analogue darbepoetin improves FMD (flow-mediated dilatation), a measure of endothelium-derived NO, and whether this is influenced by preceding I/R (ischaemia/reperfusion). A total of 36 patients (50-75 years) with stable coronary artery disease were randomized to receive a single dose of darbepoetin (300 µg) or saline placebo. FMD was measured at the brachial artery using high-resolution ultrasound. CD133⁺/CD34⁺/VEGFR2⁺ (vascular endothelial growth factor receptor 2) circulating EPCs were enumerated by flow cytometry. Measurements were made immediately before darbepoetin/placebo and at 24 h, 72 h and 7 days. At 24 h, FMD was repeated after 20 min of I/R of the upper limb. A further group of 11 patients was studied according to the same protocol, all receiving darbepoetin, with omission of forearm I/R at 24 h. Immunoreactive erythropoietin peaked at 24 h and remained elevated at approximately 50-fold of baseline at 72 h. FMD did not differ significantly between groups at 24 h (before I/R). At 72 h (48 h after I/R), FMD was greater (by 2.3±0.5% in the darbepoetin compared with the placebo group, a 66% increase over baseline; P<0.001) and greater than FMD at the same time point without preceding I/R (P<0.01). Increases in CD133⁺/CD34⁺/VEGFR2⁺ cells after darbepoetin did not differ according to the presence or absence of preceding I/R. Preceding I/R is required for darbepoetin to enhance endothelial function, possibly by increasing expression of the erythropoietin receptor and by a mechanism likely to involve Akt/NO rather than circulating EPCs.

Establishment of the Heart and Brain Team for Patent Foramen Ovale Closure in Stroke Patients: An Expert Opinion.

The online 2021 Asian-Pacific Heart and Brain Summit was organized to present and discuss experiences within leading Asian-Pacific centers with regard to institutional heart and brain teams managing the diagnosis, treatment, and follow-up of cryptogenic stroke (CS) patients with patent foramen ovale (PFO). This manuscript presents a narrative review of presentations and discussions during the summit meeting. Percutaneous PFO closure is an established therapy for CS patients in whom PFO is considered to be causal. Guidelines and consensus statements emphasize the importance of multidisciplinary clinical decision-making regarding PFO closure with the involvement of several clinical specialties, including neurology, cardiology, and hematology. It is also recommended that the patient be closely involved in this process. The heart and brain team is a collaborative platform that facilitates such a multidisciplinary decision-making process and patient involvement. It also creates opportunities for education and evaluation of the healthcare provided to patients with CS. This review provides insights into the implementation, composition, organization, and operation of a heart and brain team. Methods and metrics are suggested to evaluate the team's role. We suggest that an efficient heart and brain team can implement guideline-recommended multidisciplinary clinical decision-making with regard to PFO closure in CS patients and play an important role in the management of these patients.

The Impact of a Dedicated Chronic Total Occlusion PCI Program on Heart Team Decision Making.

BACKGROUND: Guidelines endorse a heart team (HT) approach to standardize the decision-making process for patients with complex coronary artery disease (CAD). With percutaneous treatment options for complex CAD increasing, we hypothesized that practice had changed over the past decade-and that more individuals, previously deemed too high risk for intervention, would now be referred for either surgical or percutaneous revascularization. METHODS: This observational study was conducted at St Thomas' Hospital (London, United Kingdom). All patients discussed at HT meetings were recorded and treatment recommendations audited. A subset of historic cases was selected for blinded, repeat discussion. RESULTS: From April 2018 to 2019, a total of 52 HT meetings discussing 375 cases were held. Patients tended to be male, with a majority demonstrating multivessel CAD in the context of preserved left ventricular function. SYNTAX scores were balanced across the tertiles. Thirty-five percent of patients had at least 1 chronic total occlusion (mean J-CTO, 3 [interquartile range, 2-3]), affecting the right coronary artery in 60%. Fifteen historic patients with isolated CTOs were re-presented an average of 8 years later; only 3 patients received the same outcome, with 80% now receiving a recommendation for revascularization over medical therapy. CONCLUSIONS: A dedicated program supporting complex coronary intervention is associated with a change in treatment recommendations issued by the local HT. In line with international guidelines, this might indicate that any complex or multivessel CAD should be discussed at HT meetings with, ideally, the presence of CTO operators.

The impact of dark-blood versus conventional bright-blood late gadolinium enhancement on the myocardial ischemic burden.

PURPOSE: In perfusion cardiovascular magnetic resonance (CMR), ischemic burden predicts adverse prognosis and is often used to guide revascularization. Ischemic scar tissue can cause stress perfusion defects that do not represent myocardial ischemia. Dark-blood late gadolinium enhancement (LGE) methods detect more scar than conventional bright-blood LGE, however, the impact on the myocardial ischemic burden estimation is unknown and evaluated in this study. METHODS: Forty patients with CMR stress perfusion defects and ischemic scar on both dark-blood and bright-blood LGE were included. For dark-blood LGE, phase sensitive inversion recovery imaging with left ventricular blood pool nulling was used. Ischemic scar burden was quantified for both methods using >5 standard deviations above remote myocardium. Perfusion defects were manually contoured, and the myocardial ischemic burden was calculated by subtracting the ischemic scar burden from the perfusion defect burden. RESULTS: Ischemic scar burden by dark-blood LGE was higher than bright-blood LGE (13.3 ± 7.4% vs. 10.3 ± 7.1%, p < 0.001). Dark-blood LGE derived myocardial ischemic burden was lower compared with bright-blood LGE (15.6% (IQR: 10.3 to 22.0) vs. 19.3 (10.9 to 25.5), median difference -2.0%, p < 0.001) with a mean bias of -2.8% (95% confidence intervals: -4.0 to -1.6%) and a large effect size (r = 0.62). CONCLUSION: Stress perfusion defects are associated with higher ischemic scar burden using dark-blood LGE compared with bright-blood LGE, which leads to a lower estimation of the myocardial ischemic burden. The prognostic value of using a dark-blood LGE derived ischemic burden to guide revascularization is unknown and warrants further investigation.

Physiological Impact of Afterload Reduction on Cardiac Mechanics and Coronary Hemodynamics Following Isosorbide Dinitrate Administration in Ischemic Heart Disease.

Understanding the cardiac-coronary interaction is fundamental to developing treatment strategies for ischemic heart disease. We sought to examine the impact of afterload reduction following isosorbide dinitrate (ISDN) administration on LV properties and coronary hemodynamics to further our understanding of the cardiac-coronary interaction. Novel methodology enabled real-time simultaneous acquisition and analysis of coronary and LV hemodynamics in vivo using coronary pressure-flow wires (used to derive coronary wave energies) and LV pressure-volume loop assessment. ISDN administration resulted in afterload reduction, reduced myocardial demand, and increased mechanical efficiency (all P<0.01). Correlations were demonstrated between the forward compression wave (FCW) and arterial elastance (r=0.6) following ISDN. In the presence of minimal microvascular resistance, coronary blood flow velocity exhibited an inverse relationship with LV elastance. In summary this study demonstrated a reduction in myocardial demand with ISDN, an inverse relationship between coronary blood flow velocity and LV contraction-relaxation and a direct correlation between FCW and arterial elastance. The pressure volume-loop and corresponding parameters b The pressure volume loop before (solid line) and after (broken line) Isosorbide dintrate.

Impact of coronary artery disease on contractile function and ventricular-arterial coupling during exercise: Simultaneous assessment of left-ventricular pressure-volume and coronary pressure and flow during cardiac catheterization.

Coronary artery disease (CAD) can adversely affect left ventricular (LV) performance during exercise by impairment of contractile function in the presence of increasing afterload. By performing invasive measures of LV pressure-volume and coronary pressure and flow during exercise, we sought to accurately measure this with comparison to the control group. Sixteen patients, with CCS class >II angina and CAD underwent invasive simultaneous measurement of left ventricular pressure-volume and coronary pressure and flow velocity during cardiac catheterization. Measurements performed at rest were compared with peak exercise using bicycle ergometry. The LV contractile function was measured invasively using the end-systolic pressure-volume relationship, a load independent marker of contractile function (Ees). Vascular afterload forces were derived from the ratio of LV end-systolic pressure to stroke volume to generate arterial elastance (Ea). These were combined to assess cardiovascular performance (ventricular-arterial [VA] coupling ratio [Ea/Ees]). Eleven patients demonstrated flow-limiting (FL) CAD (hyperemic Pd/Pa <0.80; ST-segment depression on exercise); five patients without flow-limiting (NFL) CAD served as the control group. Exercise in the presence of FL CAD was associated impairment of Ees, increased Ea, and deterioration of VA coupling. In the control cohort, exercise was associated with increased Ees and improved VA coupling. The backward compression wave energy directly correlated with the magnitude contraction as measured by dP/dTmax (r = 0.88, p = 0.004). This study demonstrates that in the presence of flow-limiting CAD, exercise to maximal effort can lead to impairment of LV contractile function and a deterioration in VA coupling compared to a control cohort.

Cardiac arrest, chronic total occlusion, and occluded stent in a 16-year-old boy with Kawasaki disease: a case report.

BACKGROUND: Kawasaki disease is the leading cause of premature coronary artery disease in developed countries. As such, patients may require revascularisation as children. However, there are no randomized data guiding treatment so this must be individualized. This case report describes the decision-making in a young patient requiring revascularization who had already suffered stent occlusion. CASE SUMMARY: Our patient, a 16-year-old boy with Kawasaki disease, presented with cardiac arrest during exercise. Coronary angiography showed that a proximal left anterior descending artery stent implanted at the age of 8 years had occluded some time ago and his right coronary artery was also chronically occluded. He has discussed in several Heart Team meetings and with international colleagues and a consensus reached to revascularize him surgically. DISCUSSION: It is vital that young patients with complex coronary disease are discussed in an extensive multidisciplinary setting to determine the most suitable means of treatment. The previously occluded stent was crucial in the individualized decision-making in this patient.

Comparison of fractional flow reserve, instantaneous wave-free ratio and a novel technique for assessing coronary arteries with serial lesions.

AIMS: Physiological indices such as fractional flow reserve (FFR), instantaneous wave-free ratio (iFR) and resting distal coronary to aortic pressure (Pd/Pa) are increasingly used to guide revascularisation. However, reliable assessment of individual stenoses in serial coronary disease remains an unmet need. This study aimed to compare conventional pressure-based indices, a reference Doppler-based resistance index (hyperaemic stenosis resistance [hSR]) and a recently described mathematical correction model to predict the contribution of individual stenoses in serial disease. METHODS AND RESULTS: Resting and hyperaemic pressure wire pullbacks were performed in 54 patients with serial disease. For each stenosis, FFR, iFR, and Pd/Pa were measured by the translesional gradient in each index and the predicted FFR (FFRpred) derived mathematically from hyperaemic pullback data. "True" stenosis significance by each index was assessed following PCI of the accompanying stenosis or measurements made in a large disease-free branch. In 27 patients, Doppler average peak flow velocity (APV) was also measured to calculate hSR (hSR=∆P/APV, where ∆P=translesional pressure gradient). FFR underestimated individual stenosis severity, inversely proportional to cumulative FFR (r=0.5, p<0.001). Mean errors for FFR, iFR and Pd/Pa were 33%, 20% and 24%, respectively, and 14% for FFRpred (p<0.001). Stenosis misclassification rates based on FFR 0.80, iFR 0.89 and Pd/Pa 0.91 thresholds were not significantly different (17%, 24% and 20%, respectively) but were higher than FFRpred (11%, p<0.001). Apparent and true hSR correlated strongly (r=0.87, p<0.001, mean error 0.19±0.3), with only 7% of stenoses misclassified. CONCLUSIONS: Individual stenosis severity is significantly underestimated in the presence of serial disease, using both hyperaemic and resting pressure-based indices. hSR is less prone to error but challenges in optimising Doppler signals limit clinical utility. A mathematical correction model, using data from hyperaemic pressure wire pullback, produces similar accuracy to hSR and is superior to conventional pressure-based indices.