Ischemic Threshold Research Articles

A proposed fetal risk scoring system for gestational diabetes to assist in optimising timing of delivery


 
 
 
 Background. The pathophysiology of gestational diabetes, which is related to abnormal gluocose tolerance and hyperinsulinaemia, renders standard fetal monitoring models ineffective, insufficient and inappropriate, as these models revolve around detecting and prognosticating on placenta-mediated disease rather than increased metabolic rates due to hyperinsulinaemia, functional hypoxia and ischaemic trophoblastic thresholds. To improve perinatal morbidity and mortality in gestational diabetes, there is therefore a need to introduce new prognostic parameters and scoring systems.
 Objectives. A proposed risk scoring system has been developed, based on our previous studies, to risk-categorise patients with gestational diabetes in terms of fetal outcome in view of the fact that the pathophysiology of gestational diabetes is not recognised by standard monitoring models, which revolve around placental insufficiency rather than metabolic anomalies.Methods. Patients with diabetes from four case-control studies were combined to form a total sample of 159 cases for validation of the risk scoring system. Univariate logistic regression analysis was used to assess the effect of individual risk factors with proposed cut-offs on adverse pregnancy outcome. The diagnostic accuracy of the total summative score was assessed by computing the area under the receiver operating characteristic (ROC) curve.
 Results. Four potential parameters were identified to risk-categorise fetuses in a pregnancy complicated by gestational diabetes, i.e. the myocardial performance index (MPI), the E/A ratio (early diastolic filling/late diastolic filling, a marker of diastolic dysfunction), increasing fetal weight (macrosomia), and an increased amniotic fluid index. The total score, obtained by summation of the composite scores for these parameters, ranged from 0 to 11. The total score performed as an excellent predictor of adverse outcome, evidenced by an ROC area under the curve of 0.94. A cut-point of 6 on the score confers a sensitivity of 84.2% and specificity of 90.2% for predicting adverse outcome.
 Conclusion. To our knowledge, this is the first gestational diabetes scoring system proposed to predict an adverse outcome.
 
 
 

Prolonged Ischemia Increases Complications Among High- and Low-Volume Centers in Lung Transplantation

BackgroundThe effect of prolonged allograft ischemic time on lung transplant outcomes remains controversial, with most studies associating it with increased mortality, but this effect is partly mitigated by center volume. This study sought to evaluate the mechanism of these findings and clarify the impact of ischemic time on short-term outcomes in a national sample. MethodsData on lung transplants (January 2010-Janary 2017) were extracted from the Scientific Registry of Transplant Recipients database. Ischemic time was dichotomized as prolonged ischemic time (PIT) or no PIT (N-PIT) at 6 hours. High-volume centers were defined as the top quintile. The primary outcome was 30-day, 1-year, and 3-year mortality; secondary outcomes included in-hospital complications and 72-hour oxygenation. ResultsAmong 11,809 records, there were significant differences between PIT and N-PIT recipients by demographics, lung allocation score, and donor organ metrics. In a 1:1 propensity score–matched cohort (n = 6422), PIT recipients had reduced survival compared with N-PIT at 3 years (66.5% vs 68.8%, P = .031). On multivariable analysis, this effect persisted among low-volume but not high-volume centers. PIT recipients were more likely to require reintubation, prolonged (>5 days) mechanical ventilation, hemodialysis, longer stay, and acute rejection (all P < .01). Except for reintubation, these disparities were present at both high- and low-volume centers independently. Ischemic time had no effect on 72-hour oxygenation. ConclusionsPIT remains associated with higher rates of postoperative complications and reduced short-term survival. While center volume ameliorated the survival impact, this was not achieved by reducing postoperative complications. Further research is warranted before broadening ischemic time thresholds among low-volume centers.

Effect of exercise-based cardiac rehabilitation on the ischemic threshold in patients with high-risk ischemic heart disease

Abstract Introduction Coronary artery disease is a complex condition and is not always resolved after an interventional or surgical procedure, due to the remaining obstructions in the coronary tree or the severity of the atherosclerosis, leaving anginal symptoms, ischemic threshold (IU) in the exercise, decreased cardiorespiratory fitness, and poor quality of life (QoL). Exercise-based cardiac rehabilitation programs (Ex-CRP) usually develop ischemic preconditioning mechanisms thanks to their direct anti-inflammatory, antioxidant, antithrombotic and coronary neovascularization effects, thus improving coronary reserve flow. We hypothesize that an Ex-CRP is capable of favorably impacting the UI in these patients. Therefore, the objective of this study is to evaluate the effects of an Ex-CRP on the UI in patients with high-risk ischemic heart disease. Methods Quasi-experimental study with 121 patients with ischemic threshold due to high-risk ischemic heart disease (with perfusion defects in nuclear medicine, complex coronary anatomy or partially revascularized) and presence of ischemic threshold in the exercise test. An Ex-CRP of 4–6 weeks duration was performed, consisting of supervised and monitored training concurrent with 30-minute aerobic exercise sessions at 70% of heart rate reserve, 3 times per week, supplemented with resistance exercise. and an educational understanding program for the control of risk factors and nutritional and psycho-emotional care. At the end of the program, a stress test was performed to compare the post-intervention effects and ischemic threshold was defined as the presence of angina or electrocardiographic changes of ischemia with negative ST-segment depression in 2 consecutive beats more than 80 ms from the J point. and in more than two contiguous leads. Results The 121 patients with ischemic threshold were 61±10 years old and 75% were male. On the other hand, 29.7% had a diagnosis of heart failure and an average LVEF of 53.1±12.9%. After Ex-CRP, an improvement was found in calculated VO2p (24.7±7.8 vs 34.23±7.5; p=0.000), METs at maximum effort from 7.06±2.15 to 9.78±1.14 (p&amp;lt;0.0001) and submaximal load in watts from 44±21.32 to 61±24.49; p&amp;lt;0.0001. 40.5% of the patients who were admitted with UI resolved it (absence of post-intervention ischemic diagnosis) after Ex-CRP and the remaining percentage with UI (59.5%) displaced it by 2.62 METs (p&amp;lt;0.0001). With this, the cardiovascular risk calculated by the Duke Score also decreased from −7 to −2 (p&amp;lt;0.0001), and the myocardial efficiency index improved from 8 to 6 (p&amp;lt;0.0001), strength (79±15 to 92±8%; p&amp;lt;0.0001) and QoL (65±17 vs 82±12; p&amp;lt;0.0001). Conclusions Ex-CRP had a significant effect on the resolution or displacement of the UI in patients with high-risk ischemic heart disease. In addition, it improved muscle strength, quality of life, myocardial efficiency, and reduced the cardiovascular risk index calculated by the Duke score. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Centro de Estudios e Investigaciόn FISICOL. Cúcuta, ColombiaCardioFit. CDMX, México

Editors' Note: Accuracy of CT Perfusion-Based Core Estimation of Follow-up Infarction: Effects of Time Since Last Known Well.

In a prospective multicenter study of 101 patients, Dr. Sarraj and colleagues assessed the accuracy of baseline CT perfusion (CTP) estimates of ischemic core, relative to follow-up diffusion-weighted imaging (DWI) lesion infarct volumes, in patients with ischemic stroke who achieved complete reperfusion with endovascular thrombectomy. The authors found that significant overestimation of the volume of irreversibly injured ischemic core—by 10 mL or more—was rare and was only observed in patients who presented within 90 minutes of last known well and achieved reperfusion within 120 minutes of CTP acquisition. Such overestimation also primarily occurred in the white matter. The overestimation of ischemia was eliminated by using a more conservative threshold for relative cerebral flood flow (rCBF) of <20% as opposed to the more typically used threshold of <30% in patients presenting within 90 minutes. In response, Drs. Garcia-Camba and Jacobi note that the prevalence and temporal distribution of patients with a large ischemic core (≥50 mL) was not reported; this could affect the overestimation rate in the study and potentially limit the generalizability of its findings. Replying to this, the authors note that their cohort was derived from consecutively enrolled patients at 9 high-volume thrombectomy centers and did not exclude patients from treatment based on ischemic core estimates. They note that their cohort reflects contemporary clinical practice, reporting the number of patients with different ischemic core volume thresholds, and note that overestimation rates did not vary with core size. They point to ongoing trials of thrombectomy in patients with large estimated core volumes and to the SELECT2 study, which includes CTP and noncontrast CT imaging, and will help establish if there is a ceiling to thrombectomy benefit in patients with large vessel occlusion based on noncontrast CT or CTP findings. This exchange highlights our evolving understanding of the concept and measurement of ischemic core and its changing importance in patient selection decisions for thrombectomy. In a prospective multicenter study of 101 patients, Dr. Sarraj and colleagues assessed the accuracy of baseline CT perfusion (CTP) estimates of ischemic core, relative to follow-up diffusion-weighted imaging (DWI) lesion infarct volumes, in patients with ischemic stroke who achieved complete reperfusion with endovascular thrombectomy. The authors found that significant overestimation of the volume of irreversibly injured ischemic core—by 10 mL or more—was rare and was only observed in patients who presented within 90 minutes of last known well and achieved reperfusion within 120 minutes of CTP acquisition. Such overestimation also primarily occurred in the white matter. The overestimation of ischemia was eliminated by using a more conservative threshold for relative cerebral flood flow (rCBF) of <20% as opposed to the more typically used threshold of <30% in patients presenting within 90 minutes. In response, Drs. Garcia-Camba and Jacobi note that the prevalence and temporal distribution of patients with a large ischemic core (≥50 mL) was not reported; this could affect the overestimation rate in the study and potentially limit the generalizability of its findings. Replying to this, the authors note that their cohort was derived from consecutively enrolled patients at 9 high-volume thrombectomy centers and did not exclude patients from treatment based on ischemic core estimates. They note that their cohort reflects contemporary clinical practice, reporting the number of patients with different ischemic core volume thresholds, and note that overestimation rates did not vary with core size. They point to ongoing trials of thrombectomy in patients with large estimated core volumes and to the SELECT2 study, which includes CTP and noncontrast CT imaging, and will help establish if there is a ceiling to thrombectomy benefit in patients with large vessel occlusion based on noncontrast CT or CTP findings. This exchange highlights our evolving understanding of the concept and measurement of ischemic core and its changing importance in patient selection decisions for thrombectomy.

Author Response: Accuracy of CT Perfusion-Based Core Estimation of Follow-up Infarction: Effects of Time Since Last Known Well.

We appreciate the response to our article.1 Our study cohort was derived from consecutively enrolled patients at 9 high-volume EVT centers and did not exclude patients based on ischemic core estimates. The cohort reflects contemporary clinical practice with 25 patients with ischemic core ≥30 mL, 15 patients with ischemic core ≥50 mL, and 6 with ischemic core ≥70 mL. Rates of overestimation did not vary with core size (5/25, 3/15, and 1/6 with significant overestimation). Furthermore, only 1 patient in the cohort had an ischemic core estimate ≥70 mL and a final infarct volume of <70 mL. The findings are in line with previous studies that demonstrated 5%–7% patients have an ischemic core ≥70 mL, and <3% demonstrate overestimation that would render them ineligible for the EVT.2,3 Our analysis suggested that CT perfusion estimates correlate significantly with subsequent infarct volume, significant overestimation that affects potential EVT eligibility is infrequent, and the use of time-dependent ischemic core thresholds can alleviate the issue of potential undertreatment of these patients. In the light of CT ASPECTS issues with interrater reliability that may result in significant misclassification, even after training and underestimating the extent of ischemic injury in patients presenting very early after stroke ictus,4 perfusion imaging provides more reliable estimates of early ischemic injury. Clinical trials of thrombectomy efficacy and safety in patients with large core are ongoing. The SELECT2 study obtains both noncontrast CT (NCCT) and CT perfusion imaging and therefore will help establish if there is a ceiling to thrombectomy benefit in patients with large vessel occlusion based on NCCT or perfusion imaging findings.5

Role of Bedside Transcranial Ultrasonography in the Assessment of Cerebral Hemodynamics in Decompressive Craniectomy Patients with Cranioplasty

Intracerebral hemorrhage is a leading cause of death and disability worldwide. After intracerebral hemorrhage, cerebral blood flow (CBF) becomes extremely low approaching ischemic thresholds. Concurrently, CBF velocities become strongly correlated to CBF itself post-injury. Identification of such hemodynamic disturbances can be used to predict outcome immediately post-injury when indices are measured using transcranial doppler ultrasonography (TCD). TCD permits non-invasive assessment of different CBF velocities as well as pulsatility index (PI). Abnormal measurement of such indices is believed to correlate to poor outcome. To investigate the effect of cerebral hemodynamics after cranioplasty in decompressive craniectomy patients using pre and postoperative TCD. This study is a prospective study of 3 years duration undertaken on 64 patients. All the patients were evaluated by TCDbefore and after decompressive craniectomy.All patients were evaluated by transcranial Doppler (TCD) 1 week before and 7-15 days after cranioplasty. TCD results were obtained though trans-temporal approach. Statistically significant differences between the values before and after craniectomy were detected in Peak Systolic Volume (PSV) for the Anterior Cerebral Artery (ACA) (P = 0.001), in PSV for the Middle Cerebral Artery (MCA) (P < 0.004), in Mean Bloodflow Velocity (MV) for the MCA (P < 0.003), and in PSV for the Posterior Cerebral artery (PCA) (P = 0.001) on the ipsilateral side. There were statistically significant differences between the values before and after cranioplasty in PSV for the PCA (P = 0.004), on contralateral side.After decompressive craniectomy, the PI values for the MCA decreased, on average, to 31+/- 33% of the pre-surgical value in the treated side and to 28+/- 31% on the opposite side. On the other hand, the mean PI values for the extracranial ICA reduced to 34+/- 21% of the initial values in the treated side, and to 21+/- 31% on the opposite side.Cranioplasty improved CBF velocities in all major intracrainal arteries, not only on the side of the lesion adjacent to the cranioplasty, but also in distant regions, such as in the contralateral hemisphere. Decompressive craniectomy significantly improves cerebral hemodynamics both on ipsilateral and contralateral cerebral hemispheres.Concomitantly, PI values on TCD decrease significantly postoperatively, mainly in the decompressed cerebral hemisphere, indicating reduction in cerebrovascular resistance. We conclude that cranioplasty improves neurological status and the mechanism of postoperative improvement of neurological status may be due to increased CBF velocity.

Long-term Survival Benefit From Revascularization Compared With Medical Therapy in Patients With or Without Diabetes Undergoing Myocardial Perfusion Single Photon Emission Computed Tomography.

To explore the long-term association of survival benefit from early revascularization with the magnitude of ischemia in patients with diabetes compared with those without diabetes using a large observational cohort of patients undergoing single photon emission computed tomography myocardial perfusion imaging (SPECT-MPI). Of 41,982 patients who underwent stress and rest SPECT-MPI from 1998 to 2017, 8,328 (19.8%) had diabetes. A propensity score was used to match 8,046 patients with diabetes to 8,046 patients without diabetes. Early revascularization was defined as occurring within 90 days after SPECT-MPI. The percentage of myocardial ischemia was assessed from the magnitude of reversible myocardial perfusion defect on SPECT-MPI. Over a median 10.3-year follow-up, the annualized mortality rate was higher for the patients with diabetes compared with those without diabetes (4.7 vs. 3.6%; P < 0.001). There were significant interactions between early revascularization and percent myocardial ischemia in patients with and without diabetes (all interaction P values <0.05). After adjusting for confounding variables, survival benefit from early revascularization was observed in patients with diabetes above a threshold of >8.6% ischemia and in patients without diabetes above a threshold of >12.1%. Patients with diabetes receiving insulin had a higher mortality rate (6.2 vs. 4.1%; P < 0.001), but there was no interaction between revascularization and insulin use (interaction P value = 0.405). Patients with diabetes, especially those on insulin treatment, had higher mortality rate compared with patients without diabetes. Early revascularization was associated with a mortality benefit at a lower ischemic threshold in patients with diabetes compared with those without diabetes.

Every decade counts: a narrative review of functional recovery after partial nephrectomy.

To provide a narrative review of the major advances regarding ischaemia and functional recovery after partial nephrectomy (PN), along with the ongoing controversies. Key articles reflecting major advances regarding ischaemia and functional recovery after PN were identified. Special emphasis was placed on contributions that changed perspectives about surgical management. Priority was also placed on randomized trials of off-clamp vs on-clamp cohorts. A decade ago, 'Every minute counts' was published, showing strong correlations between duration of ischaemia and development of acute kidney injury (AKI) and chronic kidney disease after clamped PN. This reinforced perspectives that ischaemia was the main modifiable factor that could be addressed to improve functional outcomes and helped spur efforts towards reduced or zero ischaemia PN. These approaches were associated with strong functional recovery and some peri-operative risk, although they were generally safe in experienced hands. Further research demonstrated that, when parenchymal volume changes were incorporated into the analyses, ischaemia lost statistical significance, and percent parenchymal volume saved proved to be the main determinant. Cold ischaemia was confirmed to be highly protective, and limited warm ischaemia also proved to be safe. The reconstructive phase of PN, with avoidance of parenchymal devascularization, appears to be most important for functional outcomes. Randomized trials of on-clamp vs off-clamp PN have shown minimal impact of ischaemia on functional recovery. The past decade has witnessed great progress regarding functional recovery after PN, with many lessons learned. However, there are still unanswered questions, including: What is the threshold of warm ischaemia at which irreversible ischaemic injury begins to develop? Are some cohorts at increased risk for AKI or irreversible ischaemic injury? and Which patients should be prioritized for zero-ischaemia PN?

Trimming of Facial Artery Myomucosal Flap (FAMM) using Indocyanine Green Fluorescence Video-Angiography: Operative Nuances.

Facial artery myomucosal flap (FAMM) is an intraoral flap pedicled on facial artery used for reconstruction of oral/oropharyngeal defects.1 Careful assessment of perfusion is essential to avoid flap necrosis, and several options are used for this purpose. Among these, indocyanine green (ICG) fluorescence video-angiography (ICG-VA) represents an innovative tool whose adoption in flap surgery is still at its early days.2 METHODS: In this multimedia article, we described the use of ICG-VA for perfusion assessment of a FAMM flap harvested for reconstruction of oral lining after ablation of a cT2cN0 floor-of-mouth (FOM) cancer. The use of ICG-VA was aimed at defining ischemic areas on the flap according to a flap-to-normal mucosa ICG ratio. After transoral excision of the FOM cancer and subsequent harvesting of a FAMM flap, we used ICG-VA to intraoperatively assess its perfusion. The degree of flap perfusion was expressed point-by-point through flap-to-normal mucosa ICG ratio (percentage); a value of 25-27% was considered as threshold for ischemia.3 Perfusion was documented both with white light modality with "overlay fluorescence" and "black and white SPY fluorescence mode" designed to increase the sensitivity of ICG detection. Small, ischemic areas were detected in the distal part of the flap and were trimmed. At the end of the procedure, an adequate perfusion was evident throughout the whole flap, allowing its safe insetting for left FOM reconstruction. Postoperative course was uneventful. ICG-VA represents a reliable tool for intraoperative detection-and trimming-of ischemic areas on reconstructive flaps.

Augmentation of perfusion with simultaneous vasodilator and inotropic agents in experimental acute middle cerebral artery occlusion: a pilot study

BackgroundThis study tests the hypothesis that simultaneous cerebral blood pressure elevation and potent vasodilation augments perfusion to ischemic tissue in acute ischemic stroke and it varies by degree of pial...

Albendazole ameliorates inflammatory response in a rat model of acute mesenteric ischemia reperfusion injury

BackgroundAcute mesenteric ischemia is known as a life threatening condition. Re-establishment of blood flow in this condition can lead to mesenteric ischemia reperfusion (MIR) injury which is accompanied by inflammatory response. Still, clear blueprint of inflammatory mechanism underlying MIR injury has not been provided. Interestingly, Albendazole has exhibited notable effects on inflammation and cytokine production. In this study, we aimed to evaluate outcomes of MIR injury following pretreatment with Albendazole with respect to assessment of mesenteric inflammation and ischemia threshold. MethodsMale rats were randomly divided into sham operated, vehicle treated, Albendazole 100 mg/kg and Albendazole 200 mg/kg groups. MIR injury was induced by occlusion of superior mesenteric artery for 30 min followed by 120 min of reperfusion. Samples were utilized for assessment of epithelial survival and villous height. Immunohistochemistry study revealed intestinal expression of TNF-α and HIF-1-α. Gene expression of NF-κB/TLR4/TNF-α/IL-6 was measured using RTPCR. Also protein levels of inflammatory cytokines in serum and intestine were assessed by ELISA method. ResultsHistopathological study demonstrated that pretreatment with Albendazole could ameliorate decline in villous height and epithelial survival following MIR injury. Also, systemic inflammation was suppressed after administration of Albendazole. Analysis of possible participating inflammatory pathway could demonstrate that intestinal expression of NF-κB/TLR4/TNF-α/IL-6 is significantly attenuated in treated groups. Eventually, IHC study illustrated concordant decline in mesenteric expression of HIF-1-α/TNF-α. ConclusionSingle dose pretreatment with Albendazole could ameliorate inflammatory response and enhance ischemia threshold following induction of MIR injury. More studies would clarify existing causality in this phenomenon.

Efficacy of Dialectical Comprehensive Treatment of Traditional Chinese Medicine in Patients with Chronic Stable Heart Failure: A Randomized Controlled Trial.

The treatment of chronic stable heart failure (CSHF) with integrated traditional Chinese and Western medicine has been of wide concern. We mainly discuss the clinical efficacy of TCM decoction combined with acupuncture and moxibustion (A&M) in CSHF treatment on the basis of syndrome differentiation and treatment (SDT). The control group was given conventional cardiac rehabilitation (CCR), and the treatment group was given TCM decoction combined with A&M treatment based on SDT on the basis of conventional cardiac rehabilitation. The clinical efficacy and cardiopulmonary exercise testing (CPET) indicators were evaluated. Left ventricular ejection fraction (LVEF), NT-proBNP, myocardial ischemia threshold (MIT), and 6-minute walking distance (6MWD) were measured by ultrasound, ELISA, electrocardiogram, and 6MWD test. After treatment, the clinical efficacy, LVEF, and 6MWD of the treatment group were better than in the control group. The NT-proBNP plasma level and MIT in the treatment group were lower than in the control group. The treatment group had enhanced AT, VO2 Peak, VO2 Peak/HR, and Peak power and decreased resting systolic pressure and peak systolic pressure, and the difference was statistically significant. Dialectical comprehensive treatment of TCM could effectively improve cardiac function and clinical treatment effect, which was worthy of clinical application.

Impact of a comprehensive cardiac rehabilitation programme versus coronary revascularization in patients with stable angina pectoris: protocol for the PRO-FIT randomised controlled trial

Abstract Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): ZonMW: The Netherlands Organisation for Health Research and Development Background Stable angina pectoris (SAP) is a highly common condition. Despite optimal medical treatment (OMT) patients often remain symptomatic and at high risk for cardiovascular morbidity and mortality. In daily practice the standard treatment consists of OMT usually followed by an invasive strategy, consisting of coronary angiography and subsequent coronary revascularization. However, recent studies showed that these costly and invasive procedures do not result in superior effects on re-events and prognosis as compared to drug therapy alone in patients with SAP. On the other hand, the effect of lifestyle-related interventions on vascular function and the progression of atherosclerotic coronary artery disease is well-known. Yet, contemporary RCTs comparing lifestyle interventions with coronary revascularization in patients with SAP are lacking. Purpose To compare the impact of a 12-month cardiac rehabilitation (CR) programme versus a routinely applied invasive approach (including coronary angiography and subsequent coronary revascularization) on anginal complaints and cost-effectiveness in SAP patients. We hypothesize that CR is at least equally effective as an invasive approach. Methods 216 SAP patients with residual anginal complaints under OMT will be randomized to usual care or a 12-month CR intervention aiming at angina relief and sustainable behavioural change for long-lasting improvement in cardiovascular health. The CR programme consists of multiple lifestyle interventions including an exercise programme, a dietary intervention and a psychoeducation module with a stepped decline in guidance by health care professionals. Patients in the CR group will receive access to an online platform, a chatbot and a smartwatch enabling patients and professionals to monitor the progress and adherence to lifestyle advices. During the first 3 months patients will receive face to face guidance, the next 3 months will consist of telerehabilitation using the smartwatch with weekly video consulting and the last 6 months will be focussed on relapse prevention and guidance on demand. The primary outcome will be the quantity of anginal complaints (evaluated by the Seattle Angina Questionnaire-7) following the 12-month intervention. Secondary outcomes include cost-effectiveness, the ischemic threshold during exercise, cardiovascular events, exercise capacity, quality of life and psychosocial wellbeing. Future implications This will be the first study evaluating a comprehensive disease-specific multimodal lifestyle intervention as a primary treatment for patients with SAP. If proven successful this study will have a great impact on the daily care of these patients as coronary revascularizations can partly be replaced by a less invasive, less costly and better sustainable treatment.

Facial Emotion Expression and the Inducibility of Myocardial Ischemia During Cardiac Stress Testing: The Role of Psychological Background Factors.

Negative emotional states, such as anger and anxiety, are associated with the onset of myocardial infarction and other acute clinical manifestations of ischemic heart disease. The likelihood of experiencing these short-term negative emotions has been associated with long-term psychological background factors such as depression, generalized anxiety, and personality factors. We examined the association of acute emotional states preceding cardiac stress testing (CST) with inducibility of myocardial ischemia and to what extent psychological background factors account for this association. Emotional states were assessed in patients undergoing CST (n = 210; mean [standard deviation] age = 66.9 [8.2] years); 91 (43%) women) using self-report measures and video recordings of facial emotion expression. Video recordings were analyzed for expressed anxiety, anger, sadness, and happiness before CST. Psychological background factors were assessed with validated questionnaires. Single-photon emission computed tomography was used to evaluate inducibility of ischemia. Ischemia occurred in 72 patients (34%). Emotional states were not associated with subsequent inducibility of ischemia during CST (odds ratio between 0.93 and 1.04; p values > .50). Psychological background factors were also not associated with ischemia (odds ratio between 0.96 and 1.06 per scale unit; p values > .20) and did not account for the associations of emotional states with ischemia. Emotional states immediately before CST and psychological background factors were not associated with the inducibility of ischemia. These findings indicate that the well-documented association between negative emotions with acute clinical manifestations of ischemic heart disease requires a different explanation than a reduced threshold for inducible ischemia.

Challenges in Diagnosis and Functional Assessment of Coronary Artery Disease in Patients With Severe Aortic Stenosis.

More than half of patients with severe aortic stenosis (AS) over 70 years old have coronary artery disease (CAD). Exertional angina is often present in AS-patients, even in the absence of significant CAD, as a result of oxygen supply/demand mismatch and exercise-induced myocardial ischemia. Moreover, persistent myocardial ischemia leads to extensive myocardial fibrosis and subsequent coronary microvascular dysfunction (CMD) which is defined as reduced coronary vasodilatory capacity below ischemic threshold. Therefore, angina, as well as noninvasive stress tests, have a low specificity and positive predictive value (PPV) for the assessment of epicardial coronary stenosis severity in AS-patients. Moreover, in symptomatic patients with severe AS exercise testing is even contraindicated. Given the limitations of noninvasive stress tests, coronary angiography remains the standard examination for determining the presence and severity of CAD in AS-patients, although angiography alone has poor accuracy in the evaluation of its functional severity. To overcome this limitation, the well-established invasive indices for the assessment of coronary stenosis severity, such as fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR), are now in focus, especially in the contemporary era with the rapid increment of transcatheter aortic valve replacement (TAVR) for the treatment of AS-patients. TAVR induces an immediate decrease in hyperemic microcirculatory resistance and a concomitant increase in hyperemic flow velocity, whereas resting coronary hemodynamics remain unaltered. These findings suggest that FFR may underestimate coronary stenosis severity in AS-patients, whereas iFR as the non-hyperemic index is independent of the AS severity. However, because resting coronary hemodynamics do not improve immediately after TAVR, the coronary vasodilatory capacity in AS-patients treated by TAVR remain impaired, and thus the iFR may overestimate coronary stenosis severity in these patients. The optimal method for evaluating myocardial ischemia in patients with AS and co-existing CAD has not yet been fully established, and this important issue is under further investigation. This review is focused on challenges, limitations, and future perspectives in the functional assessment of coronary stenosis severity in these patients, bearing in mind the complexity of coronary physiology in the presence of this valvular heart disease.

Stress perfusion cardiovascular magnetic resonance and serial fractional flow reserve assessment of the left anterior descending artery in patients undergoing right coronary artery chronic total occlusion revascularization.

BackgroundFractional flow reserve (FFR) assessment of remote arteries, in the context of a bystander chronic total occlusion (CTO), can lead to false positive results. Adenosine stress cardiovascular magnetic resonance (CMR) evaluates perfusion defects across the entire myocardium and may therefore be a reliable tool in the work-up of remote lesions in CTO patients. The IMPACT-CTO study investigated donor artery invasive physiology before, immediately post, and at 4 months following right coronary artery (RCA) CTO percutaneous coronary intervention (PCI). The aim of this subanalysis was to assess the concordance between baseline perfusion CMR and serial FFR evaluation of left anterior descending artery (LAD) ischemia in patients from the IMPACT-CTO study.MethodsBaseline adenosine stress CMR examinations from 26 patients were analyzed for qualitative evidence of LAD ischemia. The results were correlated with the serial LAD FFR measurements.ResultsThe present findings demonstrated that before RCA CTO PCI, there was 62% agreement between perfusion CMR and FFR (ischemic threshold ≤ 0.8) in the assessment of LAD ischemia (k = 0.29; fair concordance). At 4 months after revascularization, there was 77% agreement (k = 0.52; moderate concordance) between the index CMR assessment of LAD ischemia and the follow-up LAD FFR. Concordance was improved at a LAD FFR ischemic threshold of ≤ 0.75.ConclusionsIn this hypothesis generating study, baseline CMR assessment of LAD ischemia correlated better with the 4 months LAD FFR data (threshold ≤ 0.8) as compared to the FFR measurements taken prior to RCA CTO revascularization.

FFRCT and Invasive Coronary Angiography – assessing concordance in an unselected UK real world population

Abstract Background/Introduction CT coronary angiography (CTCA) Fractional Flow Reserve (FFRCT) is a key investigation in chronic coronary syndrome (CCS) guidelines. FFR calculated from CTCA may help improve CTCA specificity for flow limiting disease, preventing unnecessary invasive coronary angiography (ICA). Purpose To (1) assess the treatment planning potential of FFRCT by determining the concordance of FFRCT with an ICA +/− invasive physiological assessment for the detection of flow limiting CAD in a real world NHS setting and (2) concordance sub-analysis of concordance of invasive iFR and FFRCT. Methods A single-centre retrospective analysis of a prospectively maintained clinical CTCA database. We identified patients with CCS who had CTCA FFRCT and subsequent ICA from August 2018 to January 2021. Concordance was assessed on a per patient and per vessel basis (major epicardial vessels: left main stem [LMS], left anterior descending artery [LAD], circumflex [LCx], right coronary artery [RCA]). Two non-invasive ischaemia thresholds were examined an FFRCT ≤0.8 and &amp;lt;0.75 (2 cm distal to stenosis). This was compared to a clinical ICA assessment where a flow limiting lesion was defined as a stenosis &amp;gt;70% (or &amp;gt;50% in the LMS) and/or an end vessel iFR ≤0.89 / FFR ≤0.8. All vessels that underwent an iFR, at the interventionists discretion, were then assessed relative to their end-vessel FFRCT. Results 565 patients had a CTCA with FFRCT and 164 patients had a subsequent ICA and were suitable for analysis. On a per patient basis 69% of those referred to ICA with an FFRCT ≤0.8 of at least one major epicardial vessel had any flow limiting CAD at ICA. With an FFRCT &amp;lt;0.75 this was 73%. Table 1 illustrates the per vessel concordance. A total of 120 vessels were included in the iFR subsection analysis. The mean FFRCT was 0.71 (±0.13) and mean iFR was 0.89 (±0.1). Accuracy was 54% (95% CI 45–63%) with a sensitivity of 89% (95% CI 76–96%), specificity 32% (95% CI 22–44%), positive predictive value 45% (95% CI 40–50%) and negative predictive value of 83% (95% CI 66–92%). A Pearson's correlation coefficient of 0.23 was found. Conclusion This study demonstrated that the negative predictive value of FFRCT was excellent, including importantly for LMS analysis. The specificity on a per vessel basis was good with the exception of the LAD assessment. This may have implications for interventional planning with this imaging modality. FFRCT correlated poorly with invasive iFR in this subsection analysis although selection bias may be contributing. There remains a significant proportion of patients referred for an ICA where no flow limiting CAD is found. Funding Acknowledgement Type of funding sources: None. Table 1. Per vessel concordance analysis of potential flow limiting FFRCT relative to clinical ICA findings. Analysed with an ischaemia threshold of FFRCT ≤0.80 and &amp;lt;0.75. PPV = Positive Predictive Value. NPV = Negative Predictive Value.

Impact of vascular morphology and plaque characteristics on computed tomography derived fractional flow reserve in early stage coronary artery disease

Abstract Background FFRCT gradually decreases from the proximal to the distal part of a vessel and reach the pathological threshold for significant ischemia even in the absence of obstructive coronary artery disease (CAD). The exact mechanisms of such gradual FFRCT decline remain unknown. Purpose The aims of this study are (1) to clarify the mechanisms of the gradual decline of computed tomography (CT) derived fractional flow reserve (FFRCT); and (2) to identify the predictive factors of an FFRCT decline below the pathological value of 0.80 in no apparent CAD vessels. Methods A total of 1058 outpatients with suspected CAD and who underwent CT angiography (CTA) with FFRCT analysis between January 2017 and December 2019 were evaluated. Among them, 150 consecutive patients who had both a CTA coupled to an FFRCT analysis and an invasive angiogram showing &amp;lt;25% coronary stenosis were included for analysis. Vessels were divided into two groups according to FFRCT at the distal vessel: FFRCT &amp;gt;0.80 (n=317) and FFRCT ≤0.80 (n=114). ΔFFRCT was defined as the magnitude of the change in FFRCT from the proximal to the distal vessel. Plaque characterization and vessel morphology measurements were performed semi-automatically. Vessel constituents were characterized based on Hounsfield units (HU) into lumen volume (&amp;lt;−50 HU), non-calcified plaque (NCP) (−50–150 HU), and calcified plaque (&amp;gt;150 HU). Results FFRCT decreased continuously from the proximal to distal across the three major vessels in both FFRCT&amp;gt;0.80 and FFRCT ≤0.80 groups (Figure 1). Compared to FFRCT&amp;gt;0.80 group, NCP volume was significantly higher in all three major vessels in FFRCT ≤0.80 group (210.2±83.6 mm3 vs. 140.9±139.3 mm3 for the RCA, p=0.01; 177.5±150.2 mm3 vs. 133.2±112.2 mm3 for the LAD, p=0.04; 127.6±91.5 mm3 vs. 58.7±57.7 mm3 for the LCX, p&amp;lt;0.01). Next, we investigated the vessel parameters that correlated with ΔFFRCT. ΔFFRCT was correlated with lumen volume in FFRCT&amp;gt;0.80 group (r=−0.24, p&amp;lt;0.0001), whereas ΔFFRCT was correlated with NCP volume in FFRCT ≤0.80 group (r=0.42, p&amp;lt;0.001) (Figure 2). An NCP volume above 44.8 mm3 was the strongest predictor of distal FFRCT of ≤0.80 (area under the curve 0.69, p&amp;lt;0.0001, sensitivity 95%, specificity 39%). Conclusions FFRCT is affected by vascular morphology and plaque characteristics even in the early stage of coronary artery disease. Our study highlights that subclinical coronary artery disease strongly influences FFRCT by effects unrelated to coronary stenosis. The presence of NCP is a major predictor of the gradual decrease of FFRCT toward pathological values. Anatomical findings as vessel morphology and plaque characteristics should be taken into consideration when interpreting numerical values of FFRCT to avoid unnecessary referrals for invasive coronary angiography or percutaneous coronary intervention. Funding Acknowledgement Type of funding sources: None. Figure 1Figure 2

Cardiac Rehabilitation and Secondary Prevention Program effect in Chronic Total Occlusion Percutaneous Coronary Intervention patients

Introduction: Chronic Total Coronary Occlusion has a high risk of mortality associated with Acute Coronary Syndrome with significantly ventricular disfunction reflected in functional class patient by intolerance to perform physical effort. The Percutaneous Coronary Intervention is the gold standard approach, but in many patients this procedure is not successful. Cardiac Rehabilitation and Secondary Prevention Programs has showed improve the patient's ability to perform physical effort by its positive effect on endothelial function and promote angiogenesis, increasing the ischemic threshold. We evaluate the Cardiac Rehabilitation and Secondary Prevention program effect on myocardial performance and ischemic profile in successful and unsuccessful Chronic Total Occlusion Percutaneous Coronary Intervention patients.Materials and Methods. A non-randomized clinical trial was conducted in patients with CTCO underwent to Percutaneous Coronary Intervention (PCI). Patients were divided into two groups: 1) With successful PCI and 2) With unsuccessful PCI. All patients underwent a Sestamibi-Dipyridamole cardiac scan and stress test before and after of CRH&SP. The cardiac rehabilitation program considered 4-6 weeks of 5 weekly 30-minute training sessions with aerobic at 70% of Heart Resistance Reserve (HRR), with interspersed 3 weekly strength training sessions, as well as nutritional and Psychiatric group interventions.Results. We evaluated 25 patients with successful PCI (n = 13) and unsuccessful PCI (n = 12). For both groups, the CRH&SP showed significant improvement (p <0.05) in myocardial performance parameters, ischemic profile, and physical effort tolerance, with a Cohen's Delta ≥ 80% in Nuclear Medicine Risk, NYHA functional class, METs reached, oxygen consumption, Myocardial Efficacy Index and Duke Score.Conclusions. The CRH&SP has a high positive effect on ventricular function improvement, myocardial performance, and ischemic profile in patients with Chronic Total Coronary Occlusion.

Limited impact of warm ischemic threshold for partial nephrectomy in the robotic surgery era: A propensity score matching study.

To evaluate the association between extended (≥30min) warm ischemic time and renal function in patients undergoing robot-assisted partial nephrectomy. This multi-institutional study retrospectively recruited 1131 patients who underwent robot-assisted partial nephrectomy. Patients were classified into shorter (<30min; n=1038) and longer (≥30min; n=92) groups based on the ischemic time required, and 1:2 propensity score matching was used to minimize selection bias. The perioperative outcomes, including acute kidney injury and trifecta attainment, and mid/long-term renal function were assessed before and after matching. Patients in the longer group had tumors with a significantly larger diameter and RENAL nephrometry score. The decline in the nadir of the estimated glomerular filtration rate was significantly greater in the longer than the shorter group in the unmatched and matched cohorts (-16.2 vs -5.5%, P<0.001; 15.5 vs -9.5%, P=0.003, respectively). A higher incidence of acute kidney injury (9.8 vs 2.6%, P=0.002) was observed in the longer group before matching, whereas the difference was comparable after matching. Before matching, the decline in estimated glomerular filtration rate at 6months postoperatively was greater (-8.2 vs -5.1%, P=0.005) and trifecta attainment was lower (50.0 vs 63.5%, P<0.001) in the longer group. However, the differences were comparable for both the parameters between the groups in the matched cohort. While extended warm ischemia during robot-assisted partial nephrectomy can be demanded in case of large and complex tumors, its impact on postoperative renal function is limited.