The mid-term effect of intravascular ultrasound on endovascular interventions for lower extremity peripheral arterial disease: A systematic review and meta-analysis.

OBJECTIVE: Intravascular ultrasound (IVUS) is an important adjunctive tool for patients with lower extremity peripheral arterial disease (PAD) undergoing endovascular therapy (EVT). The evidence regarding the advantages of IVUS use is evolving, and recent studies have reported conflicting results. We aimed to perform a meta-analysis to evaluate the efficacy of IVUS during angiography-guided EVT for patients with PAD. METHODS: MEDLINE and EMBASE were searched through April 2023 to identify studies that investigated the outcomes of IVUS with angiography-guided EVT vs angiography-alone-guided EVT. The primary outcome was restenosis/occlusion rate; secondary outcomes were target lesion revascularization, major amputation, and mortality. RESULTS: One randomized controlled trial and 14 observational studies, largely of moderate quality, were included, yielding a total of 708,808 patients with 709,189 lesions that were treated with IVUS-guided EVT (n = 101,405) vs angiography-alone (n = 607,784). Compared with angiography alone, IVUS-guided EVT was associated with a non-significant trend towards decreased restenosis/occlusion (relative risk [RR], 0.74; 95% confidence interval [CI], 0.54-1.00; I2 = 60%). Although the risk of target lesion revascularization and mortality were comparable (RR, 0.85; 95% CI, 0.65-1.10; I2 = 70%; RR, 1.01; 95% CI, 0.79-1.28; I2 = 43%, respectively), the use of IVUS was also associated with significantly lower risk of major amputation (RR, 0.74; 95% CI, 0.67-0.82; I2 = 47%). Subgroup analysis focusing on femoropopliteal disease demonstrated significantly higher patency (RR, 0.72; 95% CI, 0.52-0.98; I2 = 73%). However, superiority with major amputation was not observed. CONCLUSIONS: IVUS-guided EVT for PAD may possibly be associated with a lower major amputation rate compared with angiography alone-guided EVT, although the difference in patency remained an insignificant trend in favor of IVUS-guided EVT. Adjunctive use of IVUS during EVT may be beneficial, and further prospective studies are warranted to delineate this relationship and the applicability of this technology in routine practice.

Transcatheter edge-to-edge mitral valve repair for mitral regurgitation in patients with cardiogenic shock: A systematic review and meta-analysis.

BACKGROUND: There is currently little evidence for transcatheter edge-to-edge mitral valve repair (TEER) for mitral regurgitation (MR) in patients with cardiogenic shock (CS). Therefore, this study investigated the characteristics and outcomes of CS patients who underwent TEER for MR. METHODS: PubMed, EMBASE were searched in July 2023. Case series and observational studies reporting clinical characteristics and outcomes in CS patients with MR who underwent TEER were included. We performed a one-group meta-analysis using a random effects model. RESULTS: A total of 4060 patients from 7 case series and 5 observational studies were included. The mean age was 68.2 (95% confidence interval [CI]: 64.1-72.2) years, and 41.4% of patients (95% CI: 39.1%-43.7%) were female. Pre-TEER, severe MR was present in 85.3% (95% CI: 76.1%-91.3%) of patients. Mean left ventricular ejection fraction was 36.7% (95% CI: 29.2%-44.2%), and 54.6% (95% CI: 36.9%-71.2%) of patients received mechanical circulatory support. The severity of MR post-TEER was less than 2+ in 88% (95% CI: 87%-89%) of patients. In-hospital mortality was 11% (95% CI: 10%-13%), whereas 30-day and 1-year mortality rates were 15% (95% CI: 13%-16%), and 36% (95% CI: 21%-54%), respectively. CONCLUSIONS: This systematic review and meta-analysis assessed the clinical characteristics and outcomes of TEER in CS patients with MR. TEER for MR in patients with CS has been successful in reducing MR in most of the patients, but with a high mortality rate. Randomized controlled trials of TEER for MR and CS are needed.

Association of Remdesivir use with bradycardia: A systematic review and meta-analysis.

Remdesivir has been used for coronavirus disease 2019 (COVID-19) pneumonia with oxygen requirements that do not require mechanical intubation, and several studies showed a reduction in disease duration. However, there is a concern about bradycardia as its side effect. We aimed to investigate the association between Remdesivir and bradycardia by integrating findings from prior studies. We queried PubMed and EMBASE in February 2023 and performed a meta-analysis of studies investigating bradycardia in patients who did or did not receive Remdesivir. The outcome of interest was the rate of bradycardia and in-hospital mortality. We identified eight studies involving 8993 patients, of which seven studies investigated bradycardia. Six studies were observational, one was a case-control, and one was a randomized trial. Incidence of bradycardia was 400/3480 patients (22.3%, 95% confidence interval, CI: [6.5-54.4], I2 = 99%) in the Remdesivir group and 294/5005 (9.8%, 95% CI: [2.8-29], I2 = 98.61) in the non-Remdesivir group. The odds ratio of bradycardia was 2.11 (95% CI: [1.65-2.71], I2 = 22%, p < 0.001) for the Remdesivir group. There was no difference in mortality between the two groups. Patients who received Remdesivir for COVID-19 were more likely to develop bradycardia. The effect of confounding factors should be considered to further clarify the possible association.

Extracorporeal membrane oxygenation for COVID-19-associated acute respiratory distress syndrome: A nationwide analysis.

Extracorporeal membrane oxygenation (ECMO) has been used for COVID-19-associated acute respiratory distress syndrome (ARDS). We aimed to elucidate the association between ECMO and mortality in patients with COVID-19-associated ARDS in the nationwide setting. United States National Inpatient Sample was used to identify mechanically ventilated adults for COVID-19 with ARDS. We divided them into three groups according to the use of ECMO (i.e., no-ECMO, venovenous [VV]-ECMO, and venoarterial [VA]-ECMO). The primary outcome was in-hospital mortality, while the secondary outcomes included the length of hospital stay (LOS) and the total costs during hospitalization. We performed a stepwise logistic regression, adjusting for baseline characteristics, comorbidities, and severity. We included 68 795 (mean age [SD]: 63.5 [0.1]), 3280 (mean age [SD]: 48.7 [0.5]), and 340 (mean age [SD]: 43.3 [2.1]) patients who received no-, VV-, and VA-ECMO, respectively. The logistic regression analysis did not show significant associations between the use of VV-/VA-ECMO and mortality (adjusted odds ratio with no-ECMO as reference [95% confidence interval]: 1.03 [0.86-1.24] and 1.18 [0.64-2.15], respectively). While LOS was longest with VV-ECMO, the total costs were highest with VA-ECMO. In conclusion, our study found no association between the use of ECMO and mortality of COVID-19-associated ARDS in the nationwide setting.

Outcomes of transcatheter edge-to-edge repair for atrial functional mitral regurgitation: A meta-analysis of observational studies.

BACKGROUND: Transcatheter edge-to-edge repair (TEER) may have potential benefits in the treatment of atrial functional mitral regurgitation (AFMR), but robust evidence is currently lacking. We conducted a systematic review and meta-analysis to investigate the clinical outcomes of TEER for AFMR, including comparisons to ventricular functional MR (VFMR). METHODS: MEDLINE and EMBASE were searched through January 2023 to identify studies eligible for analysis. The primary outcome was postprocedural MR severity. Postprocedural New York Heart Association (NYHA) functional class classification and all-cause mortality were also evaluated. Outcomes were stratified into short term (postprocedure to 6 months) and long term (6 months to 2 years). RESULTS: A total of eight observational studies met the inclusion criteria, enrolling 539 AFMR and 3486 VFMR patients. Postprocedural MR grade ≤2 in the AFMR group was observed in 93.7% (454/491 patients; 95% confidence interval (CI), 91.1%-96.2%, I2 = 24.3%) and 97.1% (89/93 patients; 95% CI, 92.9%-100%, I2 = 26.4%) in short- and long-term follow-up, respectively. There was no difference in the rates of postprocedural MR grade ≤2 between AFMR and VFMR either in short-term (risk ratio [RR], 1.00 [95% CI, 0.95-1.06]; p = 0.90; I2 = 53%) or long-term follow-up (RR, 1.08 [95% CI, 0.89-1.32]; p = 0.44; I2 = 22%). Similarly, no difference was observed between AFMR and VFMR in the rates of postprocedural NYHA class ≤2 or all-cause mortality. CONCLUSION: TEER provides similar clinical outcomes for AFMR and VFMR. A high rate of MR grade ≤2 was observed in patients at both short- and long-term follow-ups. Further prospective studies with TEER versus medical therapy and/or rhythm control for AFMR are warranted.

Distribution of cardiomyocyte-selective adeno-associated virus serotype 9 vectors in swine following intracoronary and intravenous infusion.

Limited reports exist regarding adeno-associated virus (AAV) biodistribution in swine. This study assessed biodistribution following antegrade intracoronary and intravenous delivery of two self-complementary serotype 9 AAV (AAV9sc) biologics designed to target signaling in the cardiomyocyte considered important for the development of heart failure. Under the control of a cardiomyocyte-specific promoter, AAV9sc.shmAKAP and AAV9sc.RBD express a small hairpin RNA for the perinuclear scaffold protein muscle A-kinase anchoring protein ß (mAKAPß) and an anchoring disruptor peptide for p90 ribosomal S6 kinase type 3 (RSK3), respectively. Quantitative PCR was used to assess viral genome (vg) delivery and transcript expression in Ossabaw and Yorkshire swine tissues. Myocardial viral delivery was 2-5 × 105 vg/µg genomic DNA (gDNA) for both infusion techniques at a dose ∼1013 vg/kg body wt, demonstrating delivery of ∼1-3 viral particles per cardiac diploid genome. Myocardial RNA levels for each expressed transgene were generally proportional to dose and genomic delivery, and comparable with levels for moderately expressed endogenous genes. Despite significant AAV9sc delivery to other tissues, including the liver, neither biologic induced toxic effects as assessed using functional, structural, and circulating cardiac and systemic markers. These results indicate successful targeted delivery of cardiomyocyte-selective viral vectors in swine without negative side effects, an important step in establishing efficacy in a preclinical experimental setting.

Catheter ablation for atrial fibrillation in elderly patients: Systematic review and a meta-analysis.

AIMS: Catheter ablation (CA) is established therapy for patients with atrial fibrillation (AF); however, there is a limited understanding of CA in elderly patients. We studied the long-term efficacy and periprocedural safety of radiofrequency and cryoballoon CA for elderly patients with AF. METHODS: PubMed and Embase were searched through April 2021 to investigate the comparative outcomes between elderly and non-elderly patients who underwent CA for AF. The primary efficacy and safety endpoints were AF recurrence and procedure-related complications, respectively. Subgroup analyses were performed by procedure type of CA. RESULTS: The search identified 20 observational studies with 110,606 patients, including 8009 elderly patients (7.2%). The risk of AF recurrence was not significantly different between elderly and non-elderly patients (hazard ratio, 1.37; 95% confidence interval [CI], 0.94-2.00; p = .10, I2  = 70%). However, relative to the non-elderly, elderly patients had significantly higher major complications (risk ratio [RR], 1.32; 95% CI, 1.14-1.54], p < .01, I2  = 0%) and overall complications (RR, 1.26; 95% CI, 1.00-1.57; p = .05, I2  = 56%) with higher cerebrovascular events (RR, 1.68; 95% CI, 1.25-2.25; p = < .01, I2  = 0%). Subgroup analysis with cryoballoon CA showed that procedure-related complications in elderly patients were similar to those in non-elderly patients but not with radiofrequency CA. CONCLUSIONS: CA for AF in elderly patients has comparable long-term efficacy compared to that in non-elderly patients; however, the incidence of procedure-related complications were higher in elderly patients. Cryoballoon CA did not confer a higher procedure-related risk in elderly patients.

Association of renin-angiotensin-aldosterone system inhibitors with mortality and testing positive of COVID-19: Meta-analysis.

Some have hypothesized that the use of angiotensin-converting enzyme inhibitors (ACEI) and angiotensin-receptor blockers (ARB) may modify susceptibility to coronavirus disease-2019 (COVID-19) in humans. Thus, we conducted two meta-analyses to investigate the effect of ACEI and ARB on mortality and susceptibility to COVID-19. Pubmed and EMBASE were searched through June 2020 to identify clinical trials that investigated the testing positive and in-hospital mortality rates for COVID-19 for those who were treated with ACEI and/or ARB and for those who were not treated with ACEI or ARB. The first analysis investigated the testing positive rate of COVID-19. The second analysis investigated the in-hospital mortality rate for patients with COVID-19. Three eligible studies for the first analysis and 14 eligible studies for the second analysis were identified. The first analysis demonstrated that the use of ACEI or ARB did not affect the testing positive rates (odds ratio [OR] [confidence interval [CI]] = 0.96 [0.88-1.04]; p = .69, OR [CI] = 0.99 [0.91-1.08]; p = 0.35, respectively). The second analysis showed that the use of ACEI and/or ARB did not affect in-hospital mortality (risk ratio [RR] 95% [CI]] = 0.88 [0.64-1.20], p = 0.42). The subgroup analysis by limiting studies of patients with hypertension showed ACEI and/or ARB use was associated with a significant reduction of in-hospital mortality compared with no ACEI or ARB use (RR [CI] = 0.66 [0.49-0.89], p = 0.004). Our analysis demonstrated that ACEI and/or ARB use was associated neither with testing positive rates of COVID-19 nor with mortality of COVID-19 patients.

Prognostic value of phase analysis on gated single photon emission computed tomography in patients with cardiac sarcoidosis.

BACKGROUND: We aimed to determine the correlation between phase analysis, reflecting the heterogeneity of perfusion defects, and the dyssynchrony of the left ventricle wall motion, and adverse cardiac events in cardiac sarcoidosis (CS) patients. METHODS: Fifty-seven consecutive patients with diagnosed CS (64 [IQR 55-71] years old, 14 males), who underwent 18F-FDG PET/CT and ECG-gated SPECT, were studied. FDG PET was analysed to measure cardiac metabolic volume (CMV), and total lesion glycolysis (TLG). The SPECT findings, such as LVEF, Summed Rest Score (SRS), bandwidth (BW) were evaluated. RESULTS: The median of BW was 56° (IQR 40-95). BW showed a strong inverse correlation with LVEF (r = - 0.60, P < 0.0001), and positive correlation with SRS (r = 0.82, P < 0.0001). However, there were no significant correlations between BW and CMV or TLG. The Kaplan-Meier curves revealed a significantly higher rate of MACE in the high BW group (BW > 56°) than the low BW group (BW ≤ 56°) (15.1%/years vs. 4.4%/years, P = 0.025). In multivariable analysis, BW was a significant independent predictor of MACE (P = 0.015). CONCLUSION: Phase analysis on gated SPECT was a significant and independent predictor of MACE in patients with CS.

The rate of myocardial perfusion recovery after steroid therapy and its implication for cardiac events in cardiac sarcoidosis and primarily preserved left ventricular ejection fraction.

BACKGROUND: Sarcoidosis is a multisystemic disorder of unknown cause characterized by immune granuloma formation in the involved organs. Few studies have reported on the myocardial perfusion changes by immunosuppression therapy in cardiac sarcoidosis (CS). Additionally, the relationship between myocardial perfusion changes and prognosis is unknown. Therefore, this study aimed to clarify myocardial perfusion recovery after steroid therapy and its prognostic value for major adverse cardiac events (MACE) in patients with CS. METHODS AND RESULTS: Thirty-eight consecutive patients with CS {median age, 63 [interquartile range (IQR) 51-68] years; 10 men} underwent both 18F-fluorodeoxyglucose positron emission tomography/computed tomography (CT) and electrocardiography-gated single-photon emission CT (SPECT) pre- and post-steroid therapy. Patients with improved or preserved myocardial perfusion after post-therapy were defined as the recovery group and those with worsened myocardial perfusion as the non-recovery group. Twenty-six patients (68%) were categorized as the recovery group. MACE occurred in eight patients. The Kaplan-Meier curves revealed a significantly higher rate of MACE in the non-recovery group (17.4%/y vs 2.9%/y, P = 0.007). CONCLUSIONS: Myocardial perfusion was recovered by steroid therapy in 61% and preserved in 8% of patients. Myocardial perfusion recovery after steroid therapy was significantly associated with a low incidence of MACE.

18F-FMISO PET/CT detects hypoxic lesions of cardiac and extra-cardiac involvement in patients with sarcoidosis.

BACKGROUND: 18F-fluoromisonidazole (FMISO) is a hypoxia positron emission tomography (PET) tracer. Here, we evaluated cardiac and extra-cardiac sarcoidosis using both FMISO and 18F-fluorodeoxyglucose (FDG) PET/CT in a prospective cohort of patients with sarcoidosis. METHODS: Ten consecutive sarcoidosis patients with suspected cardiac involvement were prospectively enrolled. Each patient fasted overnight (for ≥ 18 hours) preceded by a low-carbohydrate diet before FDG PET/CT but not given special dietary instructions before the FMISO PET/CT scan. We visually and semiquantitatively assessed the uptakes of FMISO and FDG using the maximal standardized uptake value (SUVmax). The metabolic volume (MV) of FDG was calculated as the volume within the boundary determined by the threshold (mean SUV of blood pool × 1.5). RESULTS: Nine patients showed focal FDG uptake in the myocardium and were diagnosed with cardiac sarcoidosis. Among the patients with extra-cardiac lesions, FDG uptake was seen in 8 lymph nodes and 3 lung lesions. FMISO uptake was seen in the 7 cardiac (77.8%) and 6 extra-cardiac (54.5%) lesions. None of the patients showed physiological FMISO uptake in the myocardium. The SUVmax values of the lesions with FMISO uptake were higher than those of the lesions without FMISO uptake in both the cardiac (SUVmax: 9.9, IQR: 8.4-10.0 vs 7.3, IQR: 6.3-8.2) and non-cardiac lesions (SUVmax: 17.6, IQR: 14.5-19.3 vs 6.1, IQR: 5.9-6.2; P = 0.006). The MV values of the lesions with FMISO uptake were significantly higher than those of the lesions without FMISO uptake (111.3, IQR: 78.3-135.7 vs 6.4, IQR: 1.9-23.3; P = 0.0009). CONCLUSIONS: FMISO showed no physiological myocardial uptake and did not require special preparation. FMISO PET has the potential to detect hypoxic lesions in patients with sarcoidosis.

Elevated serum endothelin-1 is an independent predictor of coronary microvascular dysfunction in non-obstructive territories in patients with coronary artery disease.

Endothelin-1 contributes to the constrictor response of the coronary arteries in patients with ischemia with normal coronary arteries. There is thus increasing evidence that endothelin-1 plays a role in coronary microvascular dysfunction (CMD). We investigated whether elevated endothelin-1 is associated with CMD in patients with coronary artery disease (CAD). We prospectively studied 49 consecutive CAD patients with 1- or 2-vessel disease (age 71 ± 10 years, 43 males). Myocardial blood flow (MBF) was measured by 15O-water PET/CT at rest and during stress, and the coronary flow reserve (CFR) was calculated by dividing the stress MBF by the rest MBF. A CFR of less than 2.0 in non-obstructive regions was defined as a marker of CMD. Eighteen out of 49 (37%) CAD patients had CMD. Endothelin-1 in patients with CMD was significantly higher than in those without CMD (2.27 ± 0.81 vs. 1.64 ± 0.48 pg/mL, P = 0.001). Accordingly, univariate ROC analysis showed that the continuous endothelin-1 levels significantly discriminated between the presence and absence of CMD (area under the curve = 0.746 [95%CI 0.592-0.899]). The dichotomous treatment of elevated endothelin-1 as 1.961 pg/mL or more yielded the optimal discriminatory capacity, with a sensitivity of 72.2% and a specificity of 71.0%. High endothelin-1 was still a significant predictor of CMD after adjusting for diabetes mellitus (odds ratio = 6.64 [1.75-25.22], P = 0.005). Endothelin-1 is associated with CMD in non-obstructive territories in patients with CAD, suggesting that endothelin-1 is a potential target for treating CMD in CAD patients.

Pre-Hematopoietic Stem Cell Transplantation Lung Computed Tomography as an Alternative to the Pulmonary Function Test during the COVID-19 Pandemic.

The pulmonary function test (PFT) is an important test for risk stratification before allogeneic transplantation (allo-HCT). However, it might be preferable to avoid PFT as much as possible in the recent era of coronavirus disease 2019 (COVID-19), because PFT requires forced expirations and might produce aerosols, increasing the risk of COVID-19 transmission. Therefore, we tried to predict normal PFT results before allo-HCT based on computed tomography (CT) findings. This study included 390 allo-HCT recipients at our center for whom lung CT images and PFT results before allo-HCT were available. Abnormal CT findings were less likely to be observed in the normal PFT group (47.0% versus 67.4%, P = .015), with a high negative predictive value of 92.9%. In a multivariate analysis, normal CT was significantly associated with normal PFT (odds ratio, 2.47; 95% confidence interval, 1.22 to 4.97; P = .012). A model for predicting normal PFT was constructed based on the results of a multivariate analysis, and the area under the curve of the receiver operating characteristic analysis was 0.656, which gave a sensitivity of 45.5% and a specificity of 86.0%. The relatively high specificity of the model suggested that PFT can be omitted in patients with normal CT findings before allo-HCT.

Impaired left ventricular global longitudinal strain is associated with elevated left ventricular filling pressure after myocardial infarction.

Left ventricular (LV) global longitudinal strain (GLS) has emerged as a significant prognostic marker in patients after myocardial infarction (MI). Although elevated LV filling pressure after MI might alter GLS, direct evidence for this is lacking. This study aimed to clarify the association between GLS and LV filling pressure in a large animal MI model. A total of 104 Yorkshire pigs underwent both echocardiographic and hemodynamic assessments 1-4 wk after induction of large anterior MI. GLS was measured in the apical four-chamber view using a semiautomated speckle-tracking software. LV pressure-volume relationship was invasively measured using a high-fidelity pressure-volume catheter. GLS >-14% was considered impaired. Compared with pigs with LV ejection fraction (LVEF) >40% and preserved GLS (n = 29), those with LVEF >40% and impaired GLS (n = 37) and those with LVEF ≤40% (n = 38) had significantly higher LV end-diastolic pressure (15.5 ± 5.5 vs. 19.7 ± 5.8 and 19.6 ± 6.6 mmHg; P = 0.008 and P = 0.026, respectively) and higher LV mean diastolic pressure (7.1 ± 2.9 vs. 10.4 ± 4.5 and 11.1 ± 5.4 mmHg; P = 0.013 and P = 0.002, respectively). GLS was modestly correlated with τ (r = 0.21, P = 0.039) and slope of LV end-diastolic pressure-volume relationship (r = 0.43, P < 0.001). Impaired GLS was associated with higher LV end-diastolic and mean-diastolic pressures after adjusting for LVEF and baseline characteristics (P = 0.026 and P = 0.001, respectively). Impaired GLS assessed by speckle-tracking echocardiography was associated with elevated LV filling pressure after MI. GLS has an incremental diagnostic value for detecting elevated LV filling pressure and may be particularly useful for evaluating post-MI patients with preserved LVEF.NEW & NOTEWORTHY Strain analysis was performed in 104 pigs after MI, and its relationship to invasive hemodynamic measurements was studied. Impaired longitudinal strain was associated with high ventricular filling pressure independent of LVEF in post-MI setting. Global longitudinal strain is a potential prognostic marker after MI.

18F-FDG uptake of the right ventricle is an important predictor of histopathologic diagnosis by endomyocardial biopsy in patients with cardiac sarcoidosis.

BACKGROUND: The aim of this study was to determine whether right ventricle (RV) 18F-fluorodeoxyglucose (FDG) uptake can predict positive findings of endomyocardial biopsy (EMB) in patients with cardiac sarcoidosis (CS). METHODS: 70 consecutive patients with clinically diagnosed CS who had undergone FDG PET were registered in the present study. Patients without EMB (n = 42) were excluded. Ultimately, 28 patients were studied. EMB samples were obtained from the RV septum. We evaluated the FDG uptake on six segments (RV, left ventricle anterior, septal, lateral, inferior, and apex). RESULTS: Positive EMB was found in six patients (21%). Patients were divided into two groups according to positive (n = 12 [43%]) or negative (n = 16 [57%]) RV FDG uptake. Patients with positive RV FDG uptake had a significantly higher frequency of positive EMB than those without (42% vs. 6%, P = 0.024). On the other hand, there was no EMB-predictive value for the FDG uptakes in the other five segments, the cardiac metabolic volume, total lesion glycolysis, left ventricular ejection fraction, or any electrocardiogram findings. CONCLUSIONS: FDG uptake of the RV but no other heart segment was associated with positive EMB in CS patients. The presence of RV FDG uptake could improve the rate of positive EMB up to 42% in patients with CS.

Quantification of myocardial blood flow with 11C-hydroxyephedrine dynamic PET: comparison with 15O-H2O PET.

BACKGROUND: 11C-hydroxyephedrine (HED) PET has been used to evaluate the myocardial sympathetic nervous system (SNS). Here we sought to establish a simultaneous approach for quantifying both myocardial blood flow (MBF) and the SNS from a single HED PET scan. METHODS: Ten controls and 13 patients with suspected cardiac disease were enrolled. The inflow rate of 11C-HED (K1) was obtained using a one-tissue-compartment model. We compared this rate with the MBF derived from 15O-H2O PET. In the controls, the relationship between K1 from 11C-HED PET and the MBF from 15O-H2O PET was linked by the Renkin-Crone model. RESULTS: The relationship between K1 from 11C-HED PET and the MBF from 15O-H2O PET from the controls' data was approximated as follows: K1  =  (1 - 0.891 * exp(- 0.146/MBF)) * MBF. In the validation set, the correlation coefficient demonstrated a significantly high relationship for both the whole left ventricle (r = 0.95, P < 0.001) and three coronary territories (left anterior descending artery: r = 0.96, left circumflex artery: r = 0.81, right coronary artery: r =  0.86; P < 0.001, respectively). CONCLUSION: 11C-HED can simultaneously estimate MBF and sympathetic nervous function without requiring an additional MBF scan for assessing mismatch areas between MBF and SNS.

Long-term Prognostic Significance of Admission Tricuspid Regurgitation Pressure Gradient in Hospitalized Patients With Heart Failure With Preserved Ejection Fraction: A Report From the Japanese Real-World Multicenter Registry.

BACKGROUND: Doppler-estimated peak systolic tricuspid regurgitation pressure gradient (TRPG) is a representative noninvasive parameter for evaluating pulmonary artery systolic pressure, which can be a determinant of adverse outcomes in chronic heart failure with preserved ejection fraction (HFpEF). However, the prognostic implications of TRPG at admission for hospitalized patients with HFpEF are undetermined. METHODS AND RESULTS: We examined 469 consecutive hospitalized patients with decompensated HFpEF (left ventricular ejection fraction ≥ 50%) who underwent TRPG measurement at admission in our HFpEF multicenter registry. The primary outcome of interest was all-cause death. Admission TRPG was significantly correlated with estimated pulmonary capillary wedge pressure and left atrial dimension (r = 0.24, P < 0.001 and r = 0.21, P < 0.001, respectively). During a median follow-up period of 748 (IQR 540-820) days, 83 patients died. Higher TRPG was significantly associated with higher mortality compared to lower TRPG (log-rank; P = 0.007). Multivariable analysis revealed that elevated TRPG was an independent determinant of mortality (HR 1.02, 95% CI 1.01-1.04, P = 0.008) after adjustment for prespecified confounders and renal function. CONCLUSIONS: Elevated TRPG at admission was an independent determinant of mortality in hospitalized patients with HFpEF, indicating that TRPG at admission could be a useful marker for risk stratification in these patients.

Use of 18F-FDG PET/CT texture analysis to diagnose cardiac sarcoidosis.

PURPOSE: 18F-fluorodeoxyglocose positron emission tomography (FDG PET) plays a significant role in the diagnosis of cardiac sarcoidosis (CS). Texture analysis is a group of computational methods for evaluating the inhomogeneity among adjacent pixels or voxels. We investigated whether texture analysis applied to myocardial FDG uptake has diagnostic value in patients with CS. METHODS: Thirty-seven CS patients (CS group), and 52 patients who underwent FDG PET/CT to detect malignant tumors with any FDG cardiac uptake (non-CS group) were studied. A total of 36 texture features from the histogram, gray-level co-occurrence matrix (GLCM), gray-level run length matrix (GLRLM), gray-level zone size matrix (GLZSM) and neighborhood gray-level difference matrix (NGLDM), were computed using polar map images. First, the inter-operator and inter-scan reproducibility of the texture features of the CS group were evaluated. Then, texture features of the patients with CS were compared to those without CS lesions. RESULTS: Twenty-eight of the 36 texture features showed high inter-operator reproducibility with intraclass correlation coefficients (ICCs) over 0.80. In addition, 17 of the 36 showed high inter-scan reproducibility with ICCs over 0.80. The SUVmax showed no difference between the CS and non-CS group [7.36 ± 2.77 vs. 8.78 ± 4.65, p = 0.45, area under the curve (AUC) = 0.60]. By contrast, 16 of the 36 texture features could distinguish CS from non-CS grsoup with AUC > 0.80. Multivariate logistic regression analysis after hierarchical clustering concluded that long-run emphasis (LRE; P = 0.0004) and short-run low gray-level emphasis (SRLGE; P = 0.016) were significant independent factors that could distinguish between the CS and non-CS groups. Specifically, LRE was significantly higher in CS than in non-CS (30.1 ± 25.4 vs. 11.4 ± 4.6, P < 0.0001), with high diagnostic ability (AUC = 0.91), and had high inter-operator reproducibility (ICC = 0.98). CONCLUSIONS: The texture analysis had high inter-operator and high inter-scan reproducibility. Some of texture features showed higher diagnostic value than SUVmax for CS diagnosis. Therefore, texture analysis may have a role in semi-automated systems for diagnosing CS.

Volume-based glucose metabolic analysis of FDG PET/CT: The optimum threshold and conditions to suppress physiological myocardial uptake.

OBJECTIVE: FDG PET/CT plays a significant role in the diagnosis of inflammatory heart diseases and cardiac tumors. We attempted to determine the optimal FDG uptake threshold for volume-based analyses and to evaluate the relationship between the myocardial physiological uptake volume in FDG PET and several clinical factors. METHODS: A total of 190 patients were retrospectively analyzed. The cardiac metabolic volume (CMV) was defined as a volume within the boundary determined by a threshold (SUVmean of blood pool × 1.5). RESULTS: The SUVmean of the blood pool measured in the descending aorta (DA) (r = 0.86, intraclass correlation coefficient [ICC] = 0.93, P < 0.0001) and that in the left ventricle (LV) cavity (r = 0.87, ICC = 0.90, P < 0.0001) showed high inter-operator reproducibility. However, the SUVmean in the LV cavity showed a significant correlation with the CMV (P = 0.0002, r = 0.26). The CMV in the patients who fasted < 18 hours were significantly higher (49.7  ±  73.2 vs. 18.0  ±  53.8 mL, P = 0.0013) compared to the patients with > 18-hour fasting. The multivariate analysis demonstrated that only the fasting period > 18 hours was independently associated with CMV = 0. CONCLUSION: Our findings revealed that the DA is suitable to decide the threshold for the volume-based analysis. The fasting time was significantly associated with the cardiac FDG uptake.

Impact of admission liver stiffness on long-term clinical outcomes in patients with acute decompensated heart failure.

Liver stiffness (LS) has been reported to be a marker of liver congestion caused by elevated central venous pressure in heart failure (HF) patients. Recent studies demonstrated that LS could be non-invasively measured by virtual touch quantification (VTQ). However, its prognostic implication in patients with acute decompensated heart failure (ADHF) is unclear. This study sought to determine whether LS measured by VTQ could be a determinant of subsequent adverse events in ADHF patients. We prospectively recruited 70 ADHF patients who underwent LS measurement by VTQ on admission in our university hospital between June 2016 and April 2018. The primary outcome of interest was the composite of all-cause mortality and worsening HF. During a median follow-up period of 272 (interquartile range 122-578) days, there were 26 (37%) events, including 5 (7%) deaths and 21 (30%) cases of worsening HF. The c-index of LS for predicting the composite of adverse events was 0.77 (95% CI 0.66-0.88), and the optimal cut-off value of LS was 1.50 m/s. Adverse events were more frequently observed in patients with high LS (≥ 1.50 m/s) compared to those with low LS (< 1.50 m/s). Multivariable Cox regression analyzes revealed that higher LS was independently associated with increased subsequent risk of adverse events after adjustment for confounders. In conclusion, high admission LS was an independent determinant of worse clinical outcomes in patients with ADHF. This finding suggests that LS on admission is useful for risk stratification of patients with ADHF.