Invasive Coronary Assessment in Myocardial Ischemia with No Obstructive Coronary Arteries.

PURPOSE OF REVIEW: The purpose of this review is threefold: (i) to give an overview of well-established invasive methods for assessing patients with ischemia with no obstructive coronary arteries (INOCA) in the cardiac catheterization laboratory; (ii) to describe the prognostic and treatment implications based on these findings, and (iii) to discuss current knowledge gaps and future perspectives. RECENT FINDINGS: Recent studies have demonstrated that invasive coronary function testing not only allows for risk stratification of patients with INOCA but also guides medical therapy with improvement in symptoms and quality of life. Based on these findings, invasive coronary function assessment is now a class 2a recommendation in the 2021 ACC/AHA chest pain guideline to improve the diagnosis of coronary microvascular dysfunction and to enhance risk stratification. Invasive functional testing for patients with INOCA is well established and easily performed in the catheterization laboratory. Comprehensive invasive assessment is a key to differentiating INOCA endotypes and optimizing both medical therapy and preventive strategies including lifestyle modification.

Diagnostic performance and prognostic impact of coronary angiography-based Index of Microcirculatory Resistance assessment: A systematic review and meta-analysis.

BACKGROUND: The Index of Microcirculatory Resistance (IMR), measured with a pressure-thermistor tipped coronary guidewire has been established as a gold standard for coronary microvascular assessment. Angiography-based IMR (angio-IMR) is a novel method to derive IMR without intracoronary instrumentation or the need for adenosine. METHODS: PubMed and Embase databases were systemically searched in November 2021 for studies that measured angio-IMR. The primary outcomes were pooled sensitivity and specificity as well as the area under the curve (AUC) of the summary receiver operating characteristic curve using IMR as a reference standard. RESULTS: A total of 129 records were initially identified and 8 studies were included in the final analysis. Overall, 1653 lesions were included in this study, of which 733 were in patients presenting with ST-segment elevation myocardial infarction. Angio-IMR yielded high diagnostic performance predicting wire-based IMR with pooled sensitivity = 0.81 (95% confidence interval: 0.76, 0.85), specificity = 0.80 (0.72, 0.86), and AUC = 0.86 (0.82, 0.88), which was similar irrespective of patient presentation. When the clinical outcome was compared between high versus low angio-IMR in patients presenting with myocardial infarction, high angio-IMR predicted an increased risk of major adverse cardiac events (MACE). CONCLUSION: Our study found that coronary angio-IMR has relatively high diagnostic performance as well as prognostic values predicting MACE, supporting its use in clinical practice.

Potential Value of Native T1 Mapping in Symptomatic Adults with Congenital Heart Disease: A Preliminary Study of 3.0 Tesla Cardiac Magnetic Resonance Imaging.

The native T1 value at 3.0 Tesla is a sensitive marker of diffuse myocardial damage. We evaluated the clinical usefulness of native T1 mapping in symptomatic adults with congenital heart disease (CHD), particularly in the systemic right ventricle (RV). Prospectively, 45 consecutive symptomatic adults with CHD were enrolled: 20 with systemic RV and 25 with tetralogy of Fallot underwent cardiac magnetic resonance (CMR) imaging at 3.0 Tesla. The Modified Look-Locker Inversion recovery sequence was used for T1 mapping. Cardiovascular events in the systemic RV were defined as heart failure and tachyarrhythmia. Brain natriuretic peptide (BNP) and indexed systemic ventricular end-diastolic volume were significantly higher in the systemic RV group. The native T1 value and extracellular volume (ECV) of the septal and lateral walls were higher in the systemic RV group, suggesting high impairment of the myocardium in the systemic RV group. There was a strong correlation between the native T1 value and ECV of the septum (r = 0.58, P = 0.03) and lateral wall (r = 0.56, P = 0.046) in the systemic RV group. Seven patients with systemic RV had cardiovascular events. In univariate logistic regression analysis, BNP and native T1 values of the insertion point were important for predicting cardiovascular events. The native T1 value at 3.0 Tesla may be a sensitive, contrast-free, and non-invasive adjunct marker of myocardial damage in CHD and predictive of cardiovascular events in the systemic RV.

Stroke volume ratio derived from magnetic resonance imaging as an indicator of interventricular dyssynchrony predicts future cardiac event in patients with biventricular Fontan circulation.

The prognostic factors in patients with biventricular heart who underwent Fontan surgery remain unclear. This study wanted to assess the hypothesis that interventricular dyssynchrony evaluated by cardiac magnetic resonance imaging (MRI) can predict future cardiac events in patients with biventricular heart who have undergone Fontan surgery. We prospectively enrolled consecutive patients with biventricular Fontan circulation from 2003 to 2016, and performed protocolized cardiac MRI. We determined the stroke volume ratio (SVr) using the following formula to assess interventricular dyssynchrony: (stroke volume (SV) of the two whole ventricles)/(SV of the right ventricle + SV of the left ventricle), by tracing cine MRI data. If interventricular dyssynchrony existed, blood flowed and returned to each ventricle through the ventricular septal defect; therefore, the SVr in this instance should be less than 1.0. We enrolled 40 patients. SVr ranged from 0.81 to 1.0 (median 0.95). Low SVr (< 0.95) was associated with worse New York Heart Association functional class, longer QRS duration, right bundle branch block, low biventricular indexed stroke volume, and low biventricular ejection fraction. During the follow-up period (median 53.5 months), 10 cardiac events occurred (six cases of acute exacerbation of heart failure, three cases of supraventricular tachycardia, and one case of exacerbation of protein-losing enteropathy). Univariate analysis showed four clinical predictors: SVr < 0.95 [hazard ratio (HR) 9.3, 95% confidential interval (CI) 1.7-171.5]; biventricular ejection fraction < 0.45 (HR 9.4, 95% CI 2.2-65.3); left ventricular indexed end-diastolic volume > 73 mL/m2 (HR 4.5, 95% CI 1.1-15.7); and the presence of the aorta directly arising from the right ventricular conus (HR 5.8, 95% CI 1.1-106). SVr derived from MRI can predict future cardiac events in Fontan patients with biventricular hearts.

Prediction of Fontan-Associated Liver Disease Using a Novel Cine Magnetic Resonance Imaging "Vortex Flow Map" in the Right Atrium.

BACKGROUND: Long-term hepatic dysfunction is an increasingly recognized complication of the Fontan operation for univentricular hearts. The purpose of this study was to determine whether Fontan-associated liver disease (FALD) could be predicted by flow dynamics in the right atrium (RA) of Fontan circulation.Methods and Results:Cardiac MRI and the serum levels of total bilirubin (TBil) and hyaluronic acid (HA) were analyzed in 36 patients who underwent an atriopulmonary connection type of Fontan operation. The mean follow-up period was 53 months. Three views (axial, coronal, and sagittal) of the cine images were scanned for the maximum cross-section of the RA obtained with1.5-Tesla scanner. We developed a "vortex flow map" to demonstrate the ratio of the circumferential voxel movement in each phase to the total movement throughout a cardiac cycle towards the center of the RA. The maximum ratio was used as the magnitude of vortex flow (MVF%) in the 3 views of the RA cine imaging. Patients with coronal MVF ≥13.6% had significantly lower free rates of TBil ≥1.8 mg/dL than those with coronal MVF <13.6% (log-rank value=4.50; P<0.05; hazard ratio=4.54). Patients with sagittal MVF ≥14.0% had significantly lower free rates of HA ≥50 ng/mL than those with coronal MVF <14.0% (log-rank value=4.40; P<0.05; hazard ratio=4.12). CONCLUSIONS: A reduced vortex flow in the RA during the late phase of the Fontan operation was associated with the development of FALD. MVF can be used as an imaging biomarker to predict FALD.

Clinical Usefulness of Coronary Flow Reserve Ratio for the Detection of Significant Coronary Artery Disease on 13N-Ammonia Positron Emission Tomography.

BACKGROUND: This study aimed to evaluate the diagnostic performance of coronary flow reserve (CFR), hyperemic myocardial blood flow (hMBF), and CFR ratio for detecting significant coronary artery disease (CAD) on 13N-ammonia positron emission tomography (PET).Methods and Results:We analyzed 63 patients (mean age, 71±9 years; 43 males) with suspected CAD who underwent both pharmacological stress/rest 13N-ammonia PET and coronary angiography. CFR and hMBF for PET were calculated automatically using quantitative PET software, and the CFR ratio was defined as the ratio of per-vessel CFR to maximum CFR in a standard 17-segment model. We compared the diagnostic performance among the 3 quantitative values. In the per-vessel analysis, 55 vessels were diagnosed as significant CAD (≥70% stenosis and/or fraction flow reserve ≤0.8). CFR, hMBF, and CFR ratio of significant CAD were significantly lower than for non-significant CAD (1.85±0.69 vs. 2.38±0.69; P<0.01, 1.67±0.54 vs. 2.19±0.52 mL·min-1·g-1; P<0.01, and 0.66±0.15 vs. 0.82±0.09; P<0.01, respectively). In the receiver-operating characteristic curve analysis, CFR, hMBF, and CFR ratio had areas under the curve of 0.71, 0.75, and 0.85 respectively, and the CFR ratio was significantly higher than CFR and hMBF (P<0.05). The sensitivity, specificity, and accuracy of the CFR ratio with an optimal cutoff value of 0.75 were 75%, 85%, and 82%, respectively. CONCLUSIONS: Clinically, the CFR ratio in 13N-ammonia PET was more effective in detecting significant CAD.

Inter- and intra-ventricular dyssynchrony in the systemic right ventricle is a surrogate marker of major cardiac events in mildly symptomatic patients.

The aim of the study was to evaluate systemic right ventricular (RV) dyssynchrony in patients with congenitally corrected transposition of the great arteries (CCTGA) and transposition of the great arteries (TGA) with New York Heart Association functional class (NYHA FC) < III. We used cardiac magnetic resonance (CMR) to evaluate the dyssynchrony and assessed whether RV dyssynchrony can be predictive of major cardiac events in their early stages in these patients. We enrolled 71 consecutive, NYHA FC < III patients with systemic RV who underwent CMR between April 1995 and December 2016. We measured intra- and inter-ventricular dyssynchrony using a feature-tracking method of cine magnetic resonance imaging. The predictors of major cardiac events were analyzed using the Cox hazard analysis. The data from 36 patients with CCTGA and 35 patients with TGA after an atrial switch were analyzed. Seven (19.4%) patients with CCTGA and 6 (17.1%) patients with TGA showed a QRS duration of ≥ 130 ms. There were significant intra- and inter-dyssynchrony in the systemic RV groups, compared to healthy controls. The average follow-up period was 5.1 ± 3.9 years. From among patients with CCTGA, 9 (25.0%) had major cardiac events. The parameters including NYHA FC, indexed RV volume, longitudinal early diastolic strain rate, and intra- and inter-ventricular dyssynchrony were predictive of major cardiac events. From among patients with TGA, 12 (34.3%) had major cardiac events. Age, NYHA FC, QRS duration, RV volume, RV mass index, LV volume, global longitudinal/circumferential strain and intraventricular dyssynchrony, were all predictive of major cardiac events. Systemic RV in NYHA FC < III patients with CCTGA and TGA, have obvious intra- and inter-dyssynchrony, suggesting ineffective wall motion and potential RV dysfunction. Intraventricular dyssynchrony can be an adjunct predictor of major cardiac events in mildly symptomatic patients with both CCTGA and TGA.

Favorable effects of early tolvaptan administration in very elderly patients after repeat hospitalizations for acute decompensated heart failure.

Tolvaptan (TLV) is an oral selective vasopressin 2 receptor antagonist that acts on the distal nephrons, causing a loss of electrolyte-free water. To date, its early administration in very elderly patients after repeat hospitalizations for acute decompensated heart failure (ADHF) despite receiving optimal medical therapy has not been evaluated. Fifty-six ADHF patients who were >80 years old and had been repeatedly hospitalized were retrospectively enrolled in this study. Twenty-five patients (14 men; mean age 86.7 ± 5.3 years; control group) received standard therapy and 31 patients (15 men; mean age 85.5 ± 4.5 years; TLV group) received oral TLV within 24 h of admission. The rate of worsening renal function was significantly lower in the TLV group than in the control group (13 vs. 40%, P < 0.05). The duration of the return to body weight at a steady state was significantly shorter in the TLV group (5.3 ± 2.8 days) than in the control group (13.9 ± 9.2 days, P < 0.01). Consequently, the hospitalization period in the TLV group (13.5 ± 5.9 days) was significantly shorter than that in the control group (24.7 ± 12.3 days, P < 0.01). In conclusion, the early administration of TLV to very elderly patients who underwent repeat hospitalizations for ADHF resulted in immediate decongestion and thus reduced the hospitalization period with a lower incidence of worsening renal function.

Beneficial effects of adaptive servo-ventilation therapy on readmission and medical costs in patients with chronic heart failure.

Adaptive servo-ventilation (ASV) therapy is a novel modality of noninvasive positive pressure ventilation and is now widely utilized to treat patients with chronic heart failure (CHF). However, there has been no clinical study of the effect of ASV therapy on readmission and cost-effectiveness for the treatment of CHF. The present study was conducted to evaluate the clinical efficacy and cost-effectiveness of home ASV therapy in 45 patients with a history of two or more admissions a year for worsening CHF. Seven patients refused to undergo chronic ASV therapy and three died. Thus, 35 patients were eventually enrolled in the present study. New York Heart Association class (2.8 ± 0.4 versus 2.3 ± 0.5, p < 0.001), log plasma B-type natriuretic peptide level (2.53 ± 0.44 versus 2.29 ± 0.40 pg/mL, p < 0.0001), left atrial dimension (47.5 ± 7.0 versus 44.9 ± 7.6 mm, p = 0.014), and mitral regurgitation area ratio (20.3 ± 12.1 versus 16.9 ± 8.9%, p = 0.007) decreased significantly after 12 months of ASV therapy. The frequency of hospitalization after ASV was significantly lower than before ASV (1.0 ± 1.0 versus 2.3 ± 0.5 times/year/patient, p < 0.0001). ASV also decreased the duration of hospitalization from 64.4 ± 46.5 to 22.8 ± 27.5 days/year/patient (p < 0.0001). Consequently, the total medical costs were reduced by 37% after ASV (1.95 ± 1.37 versus 3.11 ± 1.75 million yen/patient, p = 0.003). ASV therapy reduced readmissions and medical costs in patients with CHF.

Vortex Flow in the Right Atrium Surrogates Supraventricular Arrhythmia and Thrombus After Atriopulmonary Connection-Type Fontan Operation: Vortex Flow Analysis Using Conventional Cine Magnetic Resonance Imaging.

We developed a novel imaging technique, designated as vortex flow (VF) mapping, which presents a vortex flow visually on conventional two-dimensional (2D) cine MRI. Using it, we assessed circumferential VF patterns and influences on RA thrombus and supraventricular tachycardia (SVT) in AP connection-type Fontan circulation. Retrospectively, we enrolled 27 consecutive patients (25.1 ± 9.2 years) and 7 age-matched controls who underwent cardiac MRI. Conventional cine images acquired using a 1.5-Tesla scanner were scanned for axial and coronal cross section of the RA. We developed "vortex flow mapping" to demonstrate the ratio of the circumferential voxel movement at each phase to the total movement throughout a cardiac cycle towards the RA center. The maximum ratio was used as a magnitude of vortex flow (MVF%) in RA cine imaging. We also measured percentages of strong and weak VF areas (VFA%). Furthermore, in 10 out of 27, we compared VF between previous CMR (3.8 ± 1.5 years ago) and latest CMR. Of the patients, 15 had cardiovascular complications (Group A); 12 did not (Group B). A transaxial image showed that strong VFA% in Group A was significantly smaller than that in Group B or controls. A coronal view revealed that strong VFA% was also smaller, and weak VFA% was larger in Group A than in Group B or controls (P < 0.05, and P < 0.05). Maximum MVF% in Group A was significantly smaller than in other groups (P < 0.001). Univariate logistic analyses revealed weak VFA% on a coronal image, and serum total bilirubin level as factors affecting cardiovascular complications (Odds ratio 1.14 and 66.1, 95% CI 1.004-1.30 and 1.59-2755.6, P values < 0.05 and < 0.05, respectively). Compared to the previous CMR, smaller maximum VMF%, smaller strong VFA%, and larger weak VFA% were identified in the latest CMR. Circumferentially weak VFA% on a coronal image can be one surrogate marker of SVT and thrombus in AP connection-type Fontan circulation. This simple VF assessment is clinically useful to detect blood stagnation.

Comparison among various physiology and angiography-guided strategies for deferring percutaneous coronary intervention: A network meta-analysis.

BACKGROUND/PURPOSE: It is unclear whether coronary physiology or coronary angiography (CA)-guided strategy is the more preferable approach for deferring percutaneous coronary intervention (PCI). We sought to evaluate the clinical efficacy of various PCI strategies through a network meta-analysis of randomized controlled trials (RCTs). METHODS/MATERIALS: We searched multiple databases for RCTs investigating the impact of the following strategies for the purpose of determining whether or not to defer PCI: fractional flow reserve, instantaneous wave-free ratio, quantitative flow ratio (QFR), and CA. We conducted a network meta-analysis for trial-defined major adverse cardiovascular events (MACE), all-cause death, cardiovascular death, myocardial infarction (MI), target lesion revascularization (TLR), and stent thrombosis. We performed a subgroup analysis for those with acute coronary syndrome (ACS). RESULTS: Our search identified 12 eligible RCTs including a total of 13,177 patients. QFR-guided PCI was associated with reduced MACE, MI, and TLR compared with CA-guided PCI (relative risk (RR) 0.68; 95 % confidence interval (CI] [0.49 to 0.94], RR 0.58; 95 % CI [0.36 to 0.96], and RR 0.58; 95 % CI [0.38 to 0.91], respectively). There were no significant differences in any pairs for all-cause death, cardiovascular death, or stent thrombosis. QFR was ranked the best in most outcomes. In the subgroup analysis of the ACS cohort, there were no significant differences in MACE between any comparisons. CONCLUSIONS: QFR was associated with reduced MACE, MI, and TLR compared with CA, and ranked the best in most outcomes. However, this was not applied in the ACS cohort.

Diagnostic performances of Nonhyperemic Pressure Ratios and Coronary Angiography-Based Fractional Flow Reserve against conventional Wire-Based Fractional Flow Reserve.

BACKGROUND: Nonhyperemic pressure ratios (NHPRs) have been proposed as alternatives to fractional flow reserve (FFR) without induction of hyperemia. More recently, imaging based-FFR estimation, especially coronary angiography-derived FFR (Angio-FFR) measurement, is proposed to estimate wire-based FFR. However, little is known about the diagnostic performance of these indices against conventional FFR. AIMS: We aimed to assess and compare the diagnostic performance of both NHPRs and coronary Angio-FFR against wire-based conventional FFR. METHODS: PubMed and Embase databases were systematically searched for peer-reviewed original articles up to 08/2022. The primary outcomes were the pooled sensitivity and specificity as well as the area under the curve (AUC) of the summary receiver-operating characteristic curve of those indices. RESULTS: A total of 6693 records were identified after a literature search, including 37 reports for NHPRs and 34 for Angio-FFR. Overall, NHPRs have a lower diagnostic performance in estimating wire-based FFR with an AUC of 0.85 (0.81, 0.88) when compared with Angio-FFR of 0.95 (0.93, 0.97). When all four modalities of NHPRs (iFR, Pd/Pa, DPR, RFR) were compared, those had overlapping AUCs without major differences among each other. Similarly, when the two most commonly used Angio-FFR (QFR, FFR angio ) were compared, those had overlapping AUCs without major differences among each other. CONCLUSION: Angio-FFR may offer a better estimation of wire-based FFR than NHPRs. Our results support a wider use of Angio-FFR in the cardiac catheterization laboratory to streamline our workflow for coronary physiologic assessment. CLASSIFICATIONS: FFR,, stable ischemic disease and non-ST elevation acute coronary syndrome.

Corrigendum: Use of the index of pulmonary vascular disease for predicting longterm outcome of pulmonary arterial hypertension associated with congenital heart disease.

[This corrects the article DOI: 10.3389/fcvm.2023.1212882.].

Challenge in Diagnosis and Management of a Patient With Myocardial Bridge and Coronary Artery Spasm.

Positive ischemia by noninvasive imaging studies often results in nonobstructive disease in cardiac catheterization. In this case, we observed ischemia by nuclear stress test in only the anteroseptal area, and the apex is free of ischemia. Coronary angiogram findings were unremarkable, but intravascular ultrasound confirmed the long length of the myocardial bridge. Further testing with spasm provocation and microvascular testing showed diffuse epicardial spasm in this area of myocardial bridge without microvascular dysfunction. We observed the myocardial bridge but no microvascular dysfunction. This case illustrates the coexistence of spasm in the area of a myocardial bridge and the challenges in the medical management of these patients. (Level of Difficulty: Advanced.).

Nonhyperemic Pressure Ratios-All the Same or Nuanced Differences?

Fractional flow reserve (FFR) has become the gold standard for invasively assessing the functional significance of coronary artery disease (CAD) to guide revascularization. The amount of evidence supporting the role of FFR in the cardiac catheterization laboratory is large and still growing. However, FFR uptake in the daily practice is limited by a variety of factors such as invasive instrumentation of the coronary artery that requires extra time and need for vasodilator medications for hyperemia. In this review, we describe the details of wire-based alternatives to FFR, providing insights as to their development, clinical evidence, and limitations.

Early optical coherence tomography evaluation of donor-transmitted atherosclerosis and cardiac allograft vasculopathy: insights from a prospective, single-center study.

BACKGROUND: The impact of donor transmitted atherosclerosis as assessed by intravascular ultrasound on development and progression of cardiac allograft vasculopathy (CAV) after heart transplantation (HT) remains poorly defined in contemporary practice. In this exploratory analysis, we sought to assess the prognostic role of early qualitative assessment of donor artery morphology using optical coherence tomography (OCT) as a more sensitive imaging modality. METHODS: HT recipients were prospectively enrolled for baseline OCT imaging of the left anterior descending coronary artery. OCT findings were classified as normal, homogeneous intimal thickening, and advanced plaque characteristics. The endpoint was a composite of cardiac death, myocardial infarction, or new angiographically detectable CAV stratified by the International Society of Heart and Lung Transplantation criteria up to 4 years of follow-up. RESULTS: A total of 35 patients underwent baseline OCT of whom 51.4% had normal OCT, 14.3% had homogenous plaque, and 34.3% had advanced characteristics. There were no significant differences in baseline demographics between patients with and without normal morphology. During a mean follow-up of 3.3 ± 0.4 years, the endpoint occurred in 11 patients including 1 death, 7 CAV1, 3 CAV2, and 1 CAV3. Kaplan-Meier analysis revealed a significantly higher event rate in patients with advanced characteristics (log-rank p = 0.010). In multivariate analysis, OCT-based plaque morphology was an independent predictor of clinical events (adjusted hazard ratio 4.57, 95% confidence interval 1.50-13.92, p = 0.008) while maximal intimal thickness ≥0.5 mm was not. CONCLUSIONS: Early qualitative OCT assessment of donor coronary artery morphology appears to be a reliable marker for predicting future cardiovascular events in HT recipients. Our findings warrant more careful study in a larger cohort.