Integrating hemodynamics with ventricular and valvular remodeling in aortic stenosis. A paradigm shift in therapeutic decision making.

Aortic valve stenosis (AS) has traditionally been approached in hemodynamic terms. Although hemodynamics and symptoms have formed the basis of recommending interventional treatment in AS, other factors reflecting left ventricular and valvular and/or vascular remodeling are equally important for the prognosis and outcome of patients with AS. Left ventricular and valvular/vascular remodeling in AS do not consistently correlate with hemodynamic severity of AS. Those remodeling changes are reflected and can be detected by a variety of novel laboratory and imaging techniques, including biomarkers, echocardiography, cardiac magnetic resonance and gated Computer Tomography (CT) imaging. Taking all those elements into Heart Team therapeutic decision making in patients with AS, can significantly improve appropriate patient selection for interventional treatment and patient outcomes. We review this novel approach and propose a simple algorithm for decision making by the Heart Team, in patients with moderate or severe AS.

Predictors of Contrast Volume in Transcatheter Aortic Valve Replacement.

BACKGROUND: Contrast-induced acute kidney injury (CIAKI) is a frequent and serious complication of transcatheter aortic valve replacement (TAVR). The most important procedural risk factor for CIAKI is contrast volume. OBJECTIVES: Because contrast volume is a modifiable factor that directly predicts CIAKI, we sought to identify predictors of increased contrast volume in TAVR patients. Identification of such predictors may allow both prediction and mitigation of CIAKI risk following TAVR. METHOD: We retrospectively analyzed data from consecutive patients not on hemodialysis who underwent successful TAVR at a single US center from 2013 to 2018. Using multivariable linear regression modelling, we assessed the relationships between contrast volumes and 49 patient and procedural factors hypothesized to be potential predictors. RESULTS: In 295 patients, we identified 17 factors that independently predicted contrast volume, 10 of which contributed 90% of the complete model's r2 value. Procedure year (suggesting a learning curve), aortic insufficiency, radiation dose, prior AVR, and previous pacemaker placement were statistically the most significant predictors of CIAKI. TAVR device and diabetes were notably not predictors. CONCLUSIONS: To predict and reduce contrast use in TAVR, patients at risk for increased contrast volume may be identified using the predictors elucidated in this study. For such patients, strategies for contrast reduction and renal protection may be employed.

Role of Invasive Functional Assessment in Surgical Revascularization of Coronary Artery Disease.

In patients with stable coronary artery disease, percutaneous coronary intervention is associated with improved outcomes if the lesion is deemed significant by invasive functional assessment using fractional flow reserve. Recent studies have shown that a revascularization strategy using instantaneous wave-free ratio is noninferior to fractional flow reserve in patients with intermediate-grade stenoses. The decision to perform coronary artery bypass grafting surgery is usually based on anatomic assessment of stenosis severity by coronary angiography. The data on the role of invasive functional assessment in guiding surgical revascularization are limited. In this review, we discuss the diagnostic and prognostic significance of invasive functional assessment in patients considered for coronary artery bypass grafting. In addition, we critically discuss ongoing and future clinical trials on the role of invasive functional assessment in surgical revascularization.

It's Crowded Here - A Case of Cor Triatriatum Sinister.

The image presented is a still frame taken from a transesophageal echocardiogram of a 76-year-old male who was referred for evaluation of mitral valve disease. He was found to have a non-flow limiting membrane, dividing the left atrium into two sections, consistent with the diagnosis of cor triatriatum sinister.

Vasospastic Angina Presenting With Syncope and Chest Pain: A Case Report and Brief Literature Review.

A 65-year-old male presented to the hospital with chest pain associated with recurrent syncope. He had a history of coronary artery disease and a long-standing history of smoking. While he was hospitalized, he had an episode of chest pain during which he was found to have transient ST segment elevation in the inferior leads. He was also noted to have a brief cardiac tachyarrhythmia. Coronary arteriography revealed vasospasm of the left anterior descending artery and right coronary artery, which were relieved to a significant extent after administration of intracoronary nitroglycerin. Subsequent angiograms and fractional flow reserve studies, demonstrated underlying non-obstructive coronary artery disease at the sites of spasm. No percutaneous coronary intervention was pursued. The patient was started on a calcium channel blocker on dismissal from the hospital. Upon follow up several months later, he remained free of symptoms that brought him to the hospital.

Prasugrel versus clopidogrel for acute coronary syndromes without revascularization.

BACKGROUND: The effect of intensified platelet inhibition for patients with unstable angina or myocardial infarction without ST-segment elevation who do not undergo revascularization has not been delineated. METHODS: In this double-blind, randomized trial, in a primary analysis involving 7243 patients under the age of 75 years receiving aspirin, we evaluated up to 30 months of treatment with prasugrel (10 mg daily) versus clopidogrel (75 mg daily). In a secondary analysis involving 2083 patients 75 years of age or older, we evaluated 5 mg of prasugrel versus 75 mg of clopidogrel. RESULTS: At a median follow-up of 17 months, the primary end point of death from cardiovascular causes, myocardial infarction, or stroke among patients under the age of 75 years occurred in 13.9% of the prasugrel group and 16.0% of the clopidogrel group (hazard ratio in the prasugrel group, 0.91; 95% confidence interval [CI], 0.79 to 1.05; P=0.21). Similar results were observed in the overall population. The prespecified analysis of multiple recurrent ischemic events (all components of the primary end point) suggested a lower risk for prasugrel among patients under the age of 75 years (hazard ratio, 0.85; 95% CI, 0.72 to 1.00; P=0.04). Rates of severe and intracranial bleeding were similar in the two groups in all age groups. There was no significant between-group difference in the frequency of nonhemorrhagic serious adverse events, except for a higher frequency of heart failure in the clopidogrel group. CONCLUSIONS: Among patients with unstable angina or myocardial infarction without ST-segment elevation, prasugrel did not significantly reduce the frequency of the primary end point, as compared with clopidogrel, and similar risks of bleeding were observed. (Funded by Eli Lilly and Daiichi Sankyo; TRILOGY ACS ClinicalTrials.gov number, NCT00699998.).

Prasugrel versus clopidogrel for patients with unstable angina or non-ST-segment elevation myocardial infarction with or without angiography: a secondary, prespecified analysis of the TRILOGY ACS trial.

BACKGROUND: Treatment with prasugrel and aspirin improves outcomes compared with clopidogrel and aspirin for patients with acute coronary syndrome who have had angiography and percutaneous coronary intervention; however, no clear benefit has been shown for patients managed first with drugs only. We assessed outcomes from the TRILOGY ACS trial based on whether or not patients had coronary angiography before treatment was chosen. METHODS: TRILOGY ACS (ClinicalTrials.gov number NCT00699998) was a randomised controlled trial, done at more than 800 sites worldwide. Patients with non-ST-elevation acute coronary syndrome who were selected for management without [corrected] revascularisation were randomly assigned to clopidogrel or prasugrel.The primary endpoint was cardiovascular death, myocardial infarction, or stroke at 30 months. In the present analysis we assessed differences in the primary endpoint by angiography status and whether the effects of treatment on the primary endpoint differed between patients who had angiography before enrolment and those who had not. FINDINGS: 7243 patients younger than 75 years were included in the TRILOGY ACS primary analysis. 3085 (43%) had angiography at baseline, 4158 (57%) had not. Fewer patients who had angiography reached the primary endpoint at 30 months compared with those who did not have angiography, according to Kaplan-Meier analysis (281/3085 [12·8%] vs 480/4158 [16·5%], adjusted hazard ratio [HR] 0·63, 95% CI 0·53-0·75; p<0·0001). The proportion of patients who reached the primary endpoint was lower in the prasugrel group than in the clopidogrel group for those who had angiography (122/1524 [10·7%] vs 159/1561 [14·9%], HR 0·77, 95% CI 0·61-0·98; p=0·032) but did not differ between groups in patients who did not have angiography (242/2096 [16·3%] vs 238/2062 [16·7%], HR 1·01, 0·84-1·20; p=0·94; pinteraction=0·08). Overall, TIMI major bleeding and GUSTO severe bleeding were rare. Bleeding outcomes tended to be higher with prasugrel but did not differ significantly between treatment groups in either angiography cohort. INTERPRETATION: Among patients who had angiography who took prasugrel there were fewer cardiovascular deaths, myocardial infarctions, or strokes than in those who took clopidogrel. This result needs to be corroborated, but it is consistent with previous trials of more versus less intensive antiplatelet treatment. When angiography is done for acute coronary syndrome and anatomic coronary disease confirmed, the benefits and risks of intensive antiplatelet treatment exist whether the patient is treated with drugs or percutaneous coronary intervention. FUNDING: Daiichi Sankyo, Eli Lilly.

Left ventricular geometry and systolic function improvement after percutaneous closure of aortic prosthetic paravalvular leak.

Paravalvular leak (PVL) represents a potential complication of valve replacement surgery. The 'gold standard' treatment for patients with severe prosthetic dysfunction, hemolysis or symptoms, is surgery. Reoperative valve surgery for such patients is related to high morbidity and mortality rate. The percutaneous closure of PVL is feasible and safe, when performed at experienced interventional cardiologic centers. Herein, the case is reported of a patient who showed a significant improvement in left ventricular systolic function after transcatheter closure of an aortic prosthetic PVL with an Amplatzer duct occluder II (ADO II). A review of the current literature is also provided.

The Single-Access Technique for Impella Protected Percutaneous Coronary Intervention: A Single-Center Experience.

BACKGROUND: In this era of complex high-risk percutaneous coronary intervention (HR-PCI), mechanical support is being increasingly used. Traditionally, mechanical circulatory support with the Impella CP device requires a large-bore arterial access and an additional arterial access for the subsequent coronary intervention. We present a case series of the novel single-access for HR-PCI (SHIP) technique, in which a single arterial access is used for both mechanical support and coronary intervention. We reviewed 35 patients from June 2019 to February 2021 in whom the procedure was successfully employed in all but 1 case. In our case series, this technique appeared to be safe and feasible, and none of our patients suffered any major bleeding or vascular complications. As our experience with the procedure grew, we started employing this technique in patients presenting with ST-segment elevation myocardial infarction and cardiogenic shock. We discuss in detail the nuances of the technique, including troubleshooting, procedural characteristics, and complications, and review the currently available literature.

Predictors of high-degree atrioventricular block in patients with new-onset left bundle branch block following transcatheter aortic valve replacement.

BACKGROUND: The development of new left bundle branch block (LBBB) is frequently seen post TAVR and is a known risk factor for progression to high degree AV block. The timing and likelihood of progression into complete heart block is variable and can develop after hospital discharge. We sought to determine predictors for the development of high degree AV block in patients who developed LBBB following TAVR. METHODS: All patients between 2014 and 2019 underwent electrophysiology study after developing LBBB post TAVR. Data on these patients including baseline characteristics, echo parameters, EKG variables, HV interval, and the need for subsequent pacemaker implantation were extracted. A prolonged HV interval was defined as ≥ 65 ms. Clinically significant conduction abnormality was defined as development of high-degree AV block or clinically significant complete heart block. RESULTS: Thirty-four patients were included in our study of which 10 (29.4%) developed clinically significant heart block, while 24 (70.6%) did not. The mean HV interval for patients with clinically significant heart block was 70.1 ms vs 57.8 ms for those who did not (p = 0.022). Pre-existing first-degree heart block prior to TAVR (p = 0.026), history of AFib (p = 0.05) in addition to STS score (p = 0.037) were predictors of development of high-degree AV block in our patient population. CONCLUSIONS: In patients who develop LBBB following TAVR, HV interval, pre-existing first-degree heart block, and STS score predict progression to high-degree AV block. Performance of a routine electrophysiology study should be considered for high-risk patients who develop LBBB following TAVR.

First-in-Human Computational Preprocedural Planning of Left Main Interventions Using a New Everolimus-Eluting Stent.

Left main coronary artery stenting requires rigorous planning and optimal execution. This case series presents a new approach to left main stenting guided by preprocedural patient-specific computational simulations. Three patients with significant left main artery disease underwent simulation-guided intervention using a novel stent scaffold purpose-built for large coronary arteries. (Level of Difficulty: Advanced.).

The predictive value and evolution of N-terminal pro-B-type natriuretic peptide levels following transcutaneous aortic valve implantation.

AIMS: We sought to define the predictive value and evolution of N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels following transcutaneous aortic valve implantation (TAVI). METHODS AND RESULTS: We investigated 91 consecutive patients who underwent TAVI (59 transfemoral [TF], 32 transapical [TA]) in our institution. The balloon-expandable valve was implanted in 75 and the self-expanding in 16 patients. The baseline (within 48 hours prior to procedure), early (24-74 hours), and late (3-12 months) postprocedural NT-proBNP levels were determined. The mortality status of all patients was ascertained as of September 2010. The 30-day and 1.3(mean)-year mortality was 3% and 12% (2%, 9% in the TF and 6%, 19% in the TA group). Increased baseline (χ(2) = 5.9, P = 0.016) and early (χ(2) = 4.9, P = 0.028) NT-proBNP levels were predictive of mortality. All decrements of the NT-proBNP levels in the TF patients were significant (baseline 4,984 ± 8,106 vs. early 3,912 ± 6,551 pg/mL, P = 0.016; late 633 ± 606 pg/mL, P = 0.003). In contrast, there was a trend for the early levels to increase in the TA patients (6,423 ± 8,897 vs. 8,100 ± 10,178 pg/mL, P = 0.090), and a significant decline in the late levels as compared to baseline (1,704 ± 3,417 pg/mL, P = 0.005). CONCLUSION: NT-proBNP levels are predictive of mortality following TAVI. There is a differential early evolution of their levels between the TF and TA patients and a significant decline later in both groups.

Iloprost prevents contrast-induced nephropathy in patients with renal dysfunction undergoing coronary angiography or intervention.

BACKGROUND: The prevention of contrast-induced nephropathy, which accounts for considerable morbidity and mortality, remains a vexing problem. Contrast-induced renal vasoconstriction is believed to play a pivotal role in the pathogenesis of contrast-induced nephropathy. The aim of this study was to examine the efficacy of the prostacyclin analog iloprost in preventing contrast-induced nephropathy in patients with renal dysfunction undergoing a coronary procedure. METHODS AND RESULTS: We conducted a randomized, double-blind, placebo-controlled trial of iloprost in 208 patients with a serum creatinine concentration >or=1.4 mg/dL who underwent coronary angiography and/or intervention. Iloprost 1 ng kg(-1) min(-1) or placebo was administered intravenously beginning 30 to 90 minutes before and ending 4 hours after the procedure. Contrast-induced nephropathy was defined by an absolute increase in serum creatinine >or=0.5 mg/dL or a relative increase >or=25% measured 2 to 5 days after the procedure. Contrast-induced nephropathy occurred in 23 of the 105 patients (22%) in the control group and in 8 of the 103 patients (8%) in the iloprost group (odds ratio, 0.29; 95% confidence interval, 0.12 to 0.69; P=0.005). In the control group, the estimated glomerular filtration rate declined from 49.7+/-15.5 to 46.6+/-16.6 mL min(-1) 1.73 m(-2) (P=0.01). In the iloprost group, the estimated glomerular filtration rate increased marginally from 47.5+/-14.5 to 48.6+/-16.1 mL min(-1) 1.73 m(-2) (P=0.26). The mean absolute estimated glomerular filtration rate decline in the control group was greater than its change in the iloprost group (difference, 4.2 mL min(-1) 1.73 m(-2); 95% confidence interval, 1.1 to 7.3; P=0.008). CONCLUSIONS: Prophylactic administration of iloprost may protect against contrast-induced nephropathy in high-risk patients undergoing a coronary procedure.

Valve in Valve Trans-Catheter Aortic Valve Replacement Followed by LVAD Deactivation in the Setting of Recovered Systolic Function.

BACKGROUND: Advanced heart failure has extremely high mortality without advanced therapies (left ventricular assist device (LVAD) implantation or cardiac transplant). LVAD patients with bioprosthetic aortic valve are more prone to leaflet fusion resulting in valvular stenosis and regurgitation. CASE PRESENTATION: We present a 46-year-old patient who had LV systolic function recovery while on LVAD. However, he had a severely stenotic aortic valve bioprosthesis with leaflet fusion that had to be replaced before deactivating his LVAD. Due to high surgical risk, we performed valve-invalve Trans-Catheter Aortic Valve Replacement (TAVR) with an Evolut self-expanding valve, however, the patient had significant aortic regurgitation secondary to deployment above the bioprosthetic valve ring. We successfully deployed a second Evolut Self-expanding valve inside the ring with excellent results. This was followed by a successful LVAD deactivation next day. His LV systolic function continued to recover and he had no heart failure symptoms at 3 month follow up. In the right settings, TAVR in recovered LVAD patients with aortic stenosis as a bridge to LVAD deactivation is a viable option, especially for patients who fall in the high-risk group. CONCLUSION: To the best of our knowledge, this is the first reported case of a valve-in-valve TAVR followed by successful LVAD deactivation in the setting of recovered LV systolic function.

The Relationship of Capillary Blood Flow Assessments with Real Time Myocardial Perfusion Echocardiography to Invasively Derived Microvascular and Epicardial Assessments.

BACKGROUND: The basis for abnormal microvascular flow responses to demand stress in coronary artery disease (CAD) is affected by resistance changes at both the epicardial stenosis level and within the downstream capillary network. We hypothesized that abnormal microvascular perfusion (MVP) responses during demand stress in patients with intermediate coronary stenoses occur when fractional flow reserve (FFR) across the epicardial stenosis is normal, because of increased microvascular resistance. METHODS: In 49 coronary arteries of 41 patients with intermediate stenoses (40%-80%) who were referred for both coronary angiography and demand stress MVP assessment, invasive coronary hemodynamics were obtained across the stenosis to measure FFR, coronary flow reserve (CFR), and hyperemic microvascular resistance (HMR) during adenosine infusion. MVP in each coronary artery territory (CAT) during demand stress was evaluated by an independent expert reviewer blinded to clinical and angiographic data. RESULTS: Thirty-four of the 49 CATs with intermediate stenoses exhibited abnormal MVP. Although the sensitivity of MVP was high for detecting abnormal FFR (100%), FFR < 0.8 was observed in only 15 of the 34 vessels that exhibited abnormal MVP (positive predictive value 44%). However, HMR was abnormal in 32 of 34 vessels (94%) with abnormal MVP (positive predictive value, 94%). CONCLUSIONS: Although abnormal MVP has high sensitivity for detecting abnormal FFR, MVP is frequently abnormal when FFR is normal. In a large percentage of these patients, invasive assessments of microvascular resistance are abnormal.

Prevalence and Predictive Value of Microvascular Flow Abnormalities after Successful Contemporary Percutaneous Coronary Intervention in Acute ST-Segment Elevation Myocardial Infarction.

BACKGROUND: Although microvascular flow abnormalities have been observed following epicardial recanalization in acute ST-segment elevation myocardial infarction (STEMI), the prevalence and severity of these abnormalities in the current era of rapid percutaneous coronary intervention (PCI) has not been evaluated. The objective of this study was to assess microvascular perfusion (MVP) following successful primary PCI in patients with STEMI and how it affects clinical outcome. METHODS: In this single-center, retrospective study, 170 patients who successfully underwent emergent PCI for STEMI were assessed using real-time myocardial contrast echocardiography using a continuous infusion of intravenous commercial microbubbles (3% Definity). Three patterns of myocardial contrast replenishment were observed following intermittent high-mechanical index impulses: infarct zone replenishment within 4 sec (normal MVP), delays in contrast replenishment but normal plateau intensity (delayed MVP [dMVP]), and both delays in replenishment and reduced plateau intensity (microvascular obstruction [MVO]). Changes in left ventricular ejection fraction at 6 months and clinical event rate at 12 months (death, recurrent infarction, need for defibrillator placement, or heart failure admission) were compared. RESULTS: Normal MVP was seen in 62 patients (36%), dMVP in 49 (29%), and MVO in 59 (35%). Left anterior descending coronary artery infarct location was the only parameter independently associated with dMVP or MVO, independent of age, cardiac risk factors, door-to-dilation time, pre-PCI Thrombolysis In Myocardial Infarction flow grade, and thrombus burden. A dMVP pattern had a similar reduction in left ventricular ejection fraction as MVO at hospital discharge but had recovery of left ventricular ejection fraction at 6 months and a greater than fourfold lower event rate than the MVO group (P < .001). CONCLUSIONS: MVO and dMVP are frequently seen following contemporary successful PCI for STEMI, especially following left anterior descending coronary artery infarction. Despite a similar area at risk, a dMVP pattern has better functional recovery and clinical outcome than MVO.

Acute right ventricular myocardial infarction.

INTRODUCTION: Acute right ventricular myocardial infarction (RVMI) is observed in 30-50% of patients presenting with inferior wall myocardial infarction (MI) and, occasionally, with anterior wall MI. The clinical consequences vary from no hemodynamic compromise to severe hypotension and cardiogenic shock depending on the extent of RV ischemia. Areas covered: The pathophysiological mechanisms, diagnostic steps, and novel therapeutic approaches of acute RVMI are described. Expert commentary: Diagnosis of acute RVMI is based on physical examination, cardiac biomarkers, electrocardiography, and coronary angiography, whereas noninvasive imaging modalities (echocardiography, cardiac magnetic resonance imaging) play a complementary role. Early revascularization, percutaneous or pharmacological, represents key step in the management of RMVI. Maintenance of reasonable heart rate and atrioventricular synchrony is essential to sustain adequate cardiac output in these patients. When conventional treatment is not successful, mechanical circulatory support, including right ventricle assist devices, percutaneous cardiopulmonary support, and intra-aortic balloon pump, might be considered. The prognosis associated with RVMI is worse in the short term, compared to non-RVMI, but those patients who survive hospitalization have a relatively good long-term prognosis.

1-Year Outcomes of Transcatheter Mitral Valve Replacement in Patients With Severe Mitral Annular Calcification.

BACKGROUND: The risk of surgical mitral valve replacement in patients with severe mitral annular calcification (MAC) is high. Several patients worldwide with severe MAC have been treated successfully with transcatheter mitral valve replacement (TMVR) using balloon-expandable aortic transcatheter valves. The TMVR in MAC Global Registry is a multicenter registry that collects data on outcomes of these procedures. OBJECTIVES: The goal of this study was to evaluate 1-year outcomes in this registry. METHODS: This study was a multicenter retrospective review of clinical outcomes. RESULTS: A total of 116 extreme surgical risk patients with severe MAC underwent TMVR; 106 had a procedure date >1 year before data-lock and were included in the analysis. Their mean age was 73 ± 12 years, and 68% were female. The mean Society of Thoracic Surgeons score was 15.3 ± 11.6%, and 90% were in New York Heart Association functional class III or IV. Thirty-day and 1-year all-cause mortality was 25% and 53.7%, respectively. Most patients who survived 30 days were alive at 1 year (49 of 77 [63.6%]), and the majority (71.8%) were in New York Heart Association functional class I or II. Echocardiography data at 1 year were available in 34 patients. Mean left ventricular ejection fraction was 58.6 ± 11.2%, mean mitral valve area was 1.9 ± 0.5 cm2, mean mitral gradient was 5.8 ± 2.2 mm Hg, and 75% had zero or trace mitral regurgitation. CONCLUSIONS: TMVR with balloon-expandable aortic valves in extreme surgical risk patients with severe MAC is feasible but associated with high 30-day and 1-year mortality. Most patients who survive the 30-day post-procedural period are alive at 1 year and have sustained improvement of symptoms and transcatheter valve performance. The role of TMVR in patients with MAC requires further evaluation in clinical trials.

Comparison of Fractional Flow Reserve Assessment With Demand Stress Myocardial Contrast Echocardiography in Angiographically Intermediate Coronary Stenoses.

BACKGROUND: Real-time myocardial contrast echocardiography (RTMCE) directly measures capillary flow (CBF), which in turn is a major regulator of coronary flow and resistance during demand or hyperemic stress. Although fractional flow reserve (FFR) was developed to assess the physiological relevance of an epicardial stenosis, it assumes maximal microvascular vasodilation and minimal resistance during vasodilator stress. Therefore, we sought to determine the relationship between CBF assessed with RTMCE during stress echocardiography and FFR in intermediate coronary lesions. METHODS AND RESULTS: Sixty-seven vessels with 50% to 80% diameter stenoses by quantitative coronary angiography in 58 consecutive patients were examined with FFR and RTMCE (mean age, 60±13 years). RTMCE was performed using an incremental dobutamine (n=32) or exercise (n=26) stress protocol, and myocardial perfusion was assessed using a continuous infusion of ultrasound contrast. The presence or absence of inducible perfusion defects and wall motion abnormalities were correlated with FFR. Mean percent diameter stenosis was 60±9%. Eighteen stenoses (27%) had an FFR ≤ 0.8. Although 17 of the 18 stenoses that were FFR+ had abnormal CBF during RTMCE, 28 of the 49 stenoses (57%) that were FFR had abnormal CBF, and 24 (49%) had abnormal wall motion in the corresponding coronary artery territory during stress echocardiography. CONCLUSIONS: In a significant percentage of intermediate stenoses with normal FFR values, CBF during demand stress is reduced, resulting in myocardial ischemia.