Cardiovascular Imaging Through the Prism of Modern Metrics

Since its inception in 2008, JACC: Cardiovascular Imaging (iJACC) has served as an important publication for all contemporary aspects of cardiovascular imaging. Understanding the dissemination trends in cardiovascular imaging has traditionally been evaluated through citations that assess interest in the research community. Recently, social media, alternative metrics (Altmetrics), and other modern metrics have enabled a more broader understanding of the interests of clinical readership. Through the prism of Altmetrics, this review discusses the most impactful studies across the spectrum of cardiovascular imaging within and outside of iJACC during a 3-year period (2017 to 2019). The top 100 Altmetrics iJACC articles in this timeframe, included articles with the highest impact with the combination of high Altmetrics (median: 66; interquartile range [IQR]: 56 to 108), high citations (median: 26; IQR: 17 to 34), and high downloads (median: 9,626; IQR: 5,770 to 11,435). This review aims to provide a framework to understand how to incorporate these metrics for a modern approach to dissemination of knowledge in the field of cardiovascular imaging.     

Transcatheter Versus Surgical Aortic Valve Replacement in Patients With Rheumatic Aortic Stenosis

BackgroundPatients with rheumatic aortic stenosis (AS) were excluded from transcatheter aortic valve replacement (TAVR) trials.ObjectivesThe authors sought to examine outcomes with TAVR versus surgical aortic valve replacement (SAVR) in patients with rheumatic AS, and versus TAVR in nonrheumatic AS.MethodsThe authors identified Medicare beneficiaries who underwent TAVR or SAVR from October 2015 to December 2017, and then identified patients with rheumatic AS using prior validated International Classification of Diseases, Version 10 codes. Overlap propensity score weighting analysis was used to adjust for measured confounders. The primary study outcome was all-cause mortality. Multiple secondary outcomes were also examined.ResultsThe final study cohort included 1,159 patients with rheumatic AS who underwent aortic valve replacement (SAVR, n = 554; TAVR, n = 605), and 88,554 patients with nonrheumatic AS who underwent TAVR. Patients in the SAVR group were younger and with lower prevalence of most comorbidities and frailty scores. After median follow-up of 19 months (interquartile range: 13 to 26 months), there was no difference in all-cause mortality with TAVR versus SAVR (11.2 vs. 7.0 per 100 person-year; adjusted hazard ratio: 1.53; 95% confidence interval: 0.84 to 2.79; p = 0.2). Compared with TAVR in nonrheumatic AS, TAVR for rheumatic AS was associated with similar mortality (15.2 vs. 17.7 deaths per 100 person-years (adjusted hazard ratio: 0.87; 95% confidence interval: 0.68 to 1.09; p = 0.2) after median follow-up of 17 months (interquartile range: 11 to 24 months). None of the rheumatic TAVR patients, <11 SAVR patients, and 242 nonrheumatic TAVR patients underwent repeat aortic valve replacement (124 redo-TAVR and 118 SAVR) at follow-up.ConclusionsCompared with SAVR, TAVR could represent a viable and possibly durable option for patients with rheumatic AS.     

Native T1 Mapping for the Diagnosis of Myocardial Fibrosis in Patients With Chronic Myocardial Infarction

BackgroundMyocardial fibrosis is a fundamental process in cardiac injury. Cardiac magnetic resonance native T1 mapping has been proposed for diagnosing myocardial fibrosis without the need for gadolinium contrast. However, recent studies suggest that T1 measurements can be erroneous in the presence of intramyocardial fat.ObjectivesThe purpose of this study was to investigate whether the presence of fatty metaplasia affects the accuracy of native T1 maps for the diagnosis of myocardial replacement fibrosis in patients with chronic myocardial infarction (MI).MethodsConsecutive patients (n = 312) with documented chronic MI (>6 months old) and controls without MI (n = 50) were prospectively enrolled. Presence and size of regions with elevated native T1 and infarction were quantitatively determined (mean + 5SD) on modified look-locker inversion-recovery and delayed-enhancement images, respectively, at 3.0-T. The presence of fatty metaplasia was determined using an out-of-phase steady-state free-precession cine technique and further verified with standard fat-water Dixon methods.ResultsNative T1 mapping detected chronic MI with markedly higher sensitivity in patients with fatty metaplasia than those without fatty metaplasia (85.6% vs 13.3%) with similar specificity (100% vs 98.9%). In patients with fatty metaplasia, the size of regions with elevated T1 significantly underestimated infarct size and there was a better correlation with fatty metaplasia size than infarct size (r = 0.76 vs r = 0.49). In patients without fatty metaplasia, most of the modest elevation in T1 appeared to be secondary to subchronic infarcts that were 6 to 12 months old; the T1 of infarcts >12 months old was not different from noninfarcted myocardium.ConclusionsNative T1 mapping is poor at detecting replacement fibrosis but may indirectly detect chronic MI if there is associated fatty metaplasia. Native T1 mapping for the diagnosis and characterization of myocardial fibrosis is unreliable.     

Efficacy of treatments for VIPoma: A GTE multicentric series

BackgroundVasoactive intestinal peptide-secreting tumor (VIPoma) is a very rare, life-threatening, functioning pancreatic neuroendocrine tumor (pNET). The efficacy of antitumor therapies against functioning symptoms and tumor burden have been poorly described in VIPoma.ObjectiveDescribe the impact of treatments on the secretory syndrome, tumor burden and survival in patients with VIPoma.MethodsWe retrospectively reviewed the records of patients with VIPoma treated in seven French expert centers between 1990 and 2016. Diagnostic of VIPoma was reassessed using strict criteria. We evaluated the antisecretory efficacy (>50 % decrease of daily bowel movements), and antitumor efficacy (RECIST 1.1) of all treatments received.ResultsTwenty-two patients were included. pNETs were mostly metastatic (77 %) and classified as grade 2 (83 %). Median follow-up was 78.2 months. Surgical excision of nonmetastatic VIPoma effectively controlled the secretory syndrome. Although 4/5 patients had metastatic recurrences, all patients were alive after median post-operative follow-up of 171 months. Among the 87 treatments received for metastatic VIPoma, curative-intent surgery (n = 14), somatostatin analogs alone (n = 11), chemotherapy (n = 23), transarterial liver embolization (TALE) (n = 14), everolimus (n = 10) and sunitinib (n = 7) achieved, respectively, 100 %, 67 %, 83 %, 50 %, 20 % and 100 % antisecretory efficacy. The 5-year OS rate was 63.6 %, with pejorative impact of higher Ki-67 index (P = 0.045) and higher plasma VIP concentration (P = 0.025).ConclusionsSurgical resection of localized VIPoma is effective but rarely curative. For metastatic VIPoma, curative-intent surgery, chemotherapy and sunitinib are the therapeutic options that best combined antitumor and antisecretory efficacies.     

Intake of legumes and cardiovascular disease: A systematic review and dose–response meta-analysis

AimsTo summarize the evidence on the association between the intake of legumes and the risk of cardiovascular disease (CVD) overall, coronary heart disease (CHD) and stroke, and to identify optimal intake levels for reduced disease risk through a systematic review and dose–response meta-analysis.Data synthesisWe have systematically searched PubMed, Scopus and Web of Science up to March, 2022 for the retrieval of intervention and observational studies (PROSPERO Reg. number: CRD42021247565). Pooled relative risks (RRs) comparing extreme categories of intake were computed using random-effects models. One-stage dose–response meta-analyses were also performed using random-effects models. 22 831 articles were screened resulting in 26 eligible observational studies (21 prospective cohort and 5 case–control studies). When comparing extreme categories of intake, the consumption of legumes was inversely associated with CVD (n = 25: RR = 0.94; 95%CI:0.89,0.99) and CHD (n = 16: RR = 0.90; 95%CI:0.85,0.96), but not with stroke (n = 9: RR = 1.00; 95%CI:0.93,1.08). We further found evidence for an inverse dose–response association with CHD, increasing in magnitude up to an intake of 400 g/week, after which the benefit seems to level-off.ConclusionsThe intake of legumes was associated with a reduced risk of CVD and CHD, but not with stroke, among individuals with the highest consumption levels. An intake level of 400 g/week seemed to provide the optimal cardiovascular benefit. Further research is needed to better understand the role of legumes in stroke subtypes.     

Pleural fluid lactate as a point-of-care adjunct diagnostic aid to distinguish tuberculous and complicated parapneumonic pleural effusions during initial thoracentesis: Potential use in a tuberculosis endemic setting

BackgroundTuberculous pleural effusions (TBEs) and parapneumonic pleural effusion (PPEs) have similar clinical presentations and fluid biochemistry. A pleural biopsy is usually required to diagnose TBE but complete fluid evacuation may not be necessary, contrasting with complicated PPE (CPPE). A point-of-care test that distinguishes between TBE and CPPE enables the appropriate procedures to be performed during the initial diagnostic thoracentesis.Lactate is a metabolic product measurable by a blood-gas analyzer. This study measured pleural fluid (Pf) lactate levels in TBE and compared them with those in PPE/CPPE. We hypothesized that Pf lactate would be significantly higher in PPE because of active metabolic activities than in TBE which is driven by delayed hypersensitivity.MethodsAll patients undergoing an initial diagnostic thoracentesis over 18 months with Pf lactate measured using a calibrated point-of-care blood gas analyzer were assessed.ResultsThe diagnoses of the enrolled patients (n = 170) included TBE (n = 49), PPE (n = 47), malignancy (n = 63), and transudate (n = 11). Pf lactate level in TBE, median 3.70 (inter-quartile range 2.65–4.90) mmol/l, was significantly lower than in PPE and CPPE. In the subgroup of TBE and CPPE patients whose initial Pf pH and glucose could suggest either condition, Pf lactate was significantly higher in those with CPPE. Pf lactate (cutoff ≥7.25 mmol/l) had a sensitivity of 79.3%, specificity 100%, positive predictive value 100%, and negative predictive value 89.1% for discriminating CPPE from TBE (area under the curve 0.947, p < 0.001, 95% confidence interval 0.89–0.99).ConclusionsPoint-of-care Pf lactate measurements may have practical value in early separation of TBE or CPPE during initial thoracentesis, and warrants further investigation.     

Subcutaneous Selatogrel Inhibits Platelet Aggregation in Patients With Acute Myocardial Infarction

BackgroundOral P2Y₁₂ receptor antagonists exhibit delayed onset of platelet inhibition in patients with acute myocardial infarction (AMI). Selatogrel is a potent, highly selective, and reversible P2Y₁₂ receptor antagonist with a rapid onset and short duration of action.ObjectivesThis study sought to assess inhibition of platelet aggregation following subcutaneous administration of selatogrel in patients with AMI.MethodsPatients with AMI were randomized to a single subcutaneous dose of selatogrel of 8 or 16 mg. The primary endpoint was response to treatment (P2Y₁₂ reaction units <100; measured by VerifyNow) at 30 min post-dose. Safety was assessed up to 48 h post-injection.ResultsForty-seven patients received selatogrel 8 mg (n = 24) or 16 mg (n = 23) followed by ticagrelor (n = 43) or clopidogrel (n = 1). The proportion of responders 30 min post-dose was 91% (one-sided 97.5% confidence interval [CI]: 80% to 100%) and 96% (97.5% CI: 87% to 100%) with 8 and 16 mg, respectively (p values for responders >85% target; p = 0.142 and p = 0.009, respectively). Response rates were independent from type of AMI presentation, age, or sex. A similar response rate was observed at 15 min (8 mg: 75% [97.5% CI: 58% to 100%]; 16 mg: 91% [97.5% CI: 80% to 100%]), which was sustained at 60 min post-dose (8 mg: 75% [97.5% CI: 58% to 100%]; 16 mg: 96% [97.5% CI: 87% to 100%]). At 15 min, median P2Y₁₂ reaction units was 51 (range: 4 to 208) for 8 mg and 9 (range: 2 to 175) for 16 mg. Selatogrel was well tolerated, without major bleeding complications.ConclusionsSingle-dose subcutaneous administration of selatogrel in patients with AMI was safe and induced a profound, rapid, and dose-related antiplatelet response. (A Medical Research Study to Evaluate the Effects of ACT-246475 in Adults With Heart Attack; NCT03487445, 2018-000765-36 [EudraCT])     

Pathology and Multimodality Imaging of Acute and Chronic Femoral Stenting in Humans

ObjectivesThe objective of this study was to comprehensively evaluate the pathology of acute and chronic femoral stenting in symptomatic atherosclerotic patients and to understand the causes of stent failure (SF) using multimodality imaging including micro–computed tomography.BackgroundAlthough the pathology of coronary stenting has been well studied, the pathology of lower extremity femoral stenting remains poorly understood.MethodsTwelve stented femoral lesions removed at surgery (n = 10) and at autopsy (n = 2) were obtained from 10 patients (median age 74 years; interquartile range [IQR]: 66 to 82 years) with histories of peripheral artery disease (critical limb ischemia in 7) (7 men and 3 women). All specimens underwent radiography, micro–computed tomography, and histological assessment.ResultsThe median duration of implantation was 150 days (IQR: 30 to 365 days), the median stent diameter was 5.90 mm (IQR: 5.44 to 7.16 mm), and the median stent length was 39.5 mm (IQR: 27 to 107.5 mm). Of the 12 stented lesions, 2 had drug-eluting stents, and 10 had bare-metal stents. SF was observed in 8 of 12 lesions. The major cause of SF was acute thrombosis (6 of 8), but causes varied (delayed healing, stent underexpansion, false lumen stenting, and fracture), and 2 had restenosis. Stent fractures were observed in 3 cases by micro–computed tomography. Both drug-eluting stents, implanted for >1 year, showed delayed healing with circumferential peristrut fibrin deposition and SF.ConclusionsThis histological study is the first to examine the pathological cause of SF. Stent thrombosis was the major cause of SF. Delayed healing was a common feature of bare-metal stents implanted for <90 days, while all drug-eluting stents, despite implantation duration >1 year, showed delayed healing.     

Impact of etiology on disease course in chronic pancreatitis

BackgroundComplications in chronic pancreatitis (CP) can be grouped in inflammatory (ICC) and fibrotic (FCC) clusters and pancreatic insufficiency cluster (PIC). However, the association between etiological risk factors and the development of complication clusters remains obscure. In this study, the impact of the etiology and disease duration on disease onset and development of complications was investigated.MethodsThis cross-sectional study recruited patients with CP from Mannheim/Germany (n = 870), Gieβen/Germany (n = 100) und Donetsk/Ukraine (n = 104). Etiological risk factors, disease stage, age at disease onset, complications, need for hospitalization and surgery were noted.ResultsIn 1074 patients diagnosed with CP, main risk factors were alcohol and nicotine abuse. An earlier onset of the disease was observed upon nicotine abuse (−4.0 years). Alcohol abuse was only associated with an earlier onset of the definite stage of CP.Alcohol abuse was the major risk factor for the development of ICC (p < 0.0001, multiple regression modeling). Abstinence of alcohol reduced ICC, whereas abstinence of nicotine showed no association. PIC correlated with efferent duct abnormalities and the disease duration. In contrast, FCC was mainly dependent on the disease duration (p < 0.0001; t-test). The presence of any complication cluster correlated with the need for surgery (p < 0.01; X²-test). However, only ICC correlated with a prolonged hospital stay (p < 0.05; t-test).ConclusionsICC is mainly dependent on alcohol abuse. In contrast, FCC and PIC are mainly dependent on the disease duration. The etiology and disease duration can be used as predictors of the course of disease to provide individual treatment and surveillance strategies.     

Safety of Revascularization Deferral of Left Main Stenosis Based on Instantaneous Wave-Free Ratio Evaluation

ObjectivesThe aim of this study was to assess the long-term clinical outcomes of patients with left main coronary artery (LM) stenosis in whom treatment strategy was based on the instantaneous wave-free ratio (iFR).BackgroundThe overall safety of iFR to guide revascularization decision making in patients with stable coronary artery disease has been established. However, no study has examined the safety of deferral of revascularization of LM disease on the basis of iFR.MethodsThis multicenter observational study included 314 patients in whom LM stenosis was deferred (n = 163 [51.9%]) or revascularized (n = 151 [48.1%]) according to the iFR cutoff ≤0.89. The primary endpoint was a composite of all-cause death, nonfatal myocardial infarction, and ischemia-driven target lesion revascularization. The secondary endpoints were each individual component of the primary endpoint and also cardiac death.ResultsAt a median follow-up period of 30 months, the primary endpoint occurred in 15 patients (9.2%) in the deferred group and 22 patients (14.6%) in the revascularized group (hazard ratio: 1.45; 95% confidence interval: 0.75 to 2.81; p = 0.26), indicating no evidence of a significant difference between the 2 groups. For the secondary endpoints, findings in the iFR-based deferral and revascularization groups were as follows: all-cause death, 3.7% versus 4.6%; cardiac death, 1.2% versus 2.0%; nonfatal myocardial infarction, 2.5% versus 5.3%; and target lesion revascularization, 4.3% versus 5.3% (p > 0.05 for all).ConclusionsDeferral of revascularization of LM stenosis on the basis of iFR appears to be safe, with similar long-term outcomes to those in patients in whom LM revascularization was performed according to iFR values.     

Intravascular Polarimetry in Patients With Coronary Artery Disease

ObjectivesThe aims of this first-in-human pilot study of intravascular polarimetry were to investigate polarization properties of coronary plaques in patients and to examine the relationship of these features with established structural characteristics available to conventional optical frequency domain imaging (OFDI) and with clinical presentation.BackgroundPolarization-sensitive OFDI measures birefringence and depolarization of tissue together with conventional cross-sectional optical frequency domain images of subsurface microstructure.MethodsThirty patients undergoing polarization-sensitive OFDI (acute coronary syndrome, n = 12; stable angina pectoris, n = 18) participated in this study. Three hundred forty-two cross-sectional images evenly distributed along all imaged coronary arteries were classified into 1 of 7 plaque categories according to conventional OFDI. Polarization features averaged over the entire intimal area of each cross section were compared among plaque types and with structural parameters. Furthermore, the polarization properties in cross sections (n = 244) of the fibrous caps of acute coronary syndrome and stable angina pectoris culprit lesions were assessed and compared with structural features using a generalized linear model.ResultsThe median birefringence and depolarization showed statistically significant differences among plaque types (p < 0.001 for both, one-way analysis of variance). Depolarization differed significantly among individual plaque types (p < 0.05), except between normal arteries and fibrous plaques and between fibrofatty and fibrocalcified plaques. Caps of acute coronary syndrome lesions and ruptured caps exhibited lower birefringence than caps of stable angina pectoris lesions (p < 0.01). In addition to clinical presentation, cap birefringence was also associated with macrophage accumulation as assessed using normalized SD.ConclusionsIntravascular polarimetry provides quantitative metrics that help characterize coronary arterial tissues and may offer refined insight into coronary arterial atherosclerotic lesions in patients.     

Prospective Study of TMVR Using Balloon-Expandable Aortic Transcatheter Valves in MAC: MITRAL Trial 1-Year Outcomes

ObjectivesThe aim of this study was to evaluate 1-year outcomes of valve–in–mitral annular calcification (ViMAC) in the MITRAL (Mitral Implantation of Transcatheter Valves) trial.BackgroundThe MITRAL trial is the first prospective study evaluating the feasibility of ViMAC using balloon-expandable aortic transcatheter heart valves.MethodsA multicenter prospective study was conducted, enrolling high-risk surgical patients with severe mitral annular calcification and symptomatic severe mitral valve dysfunction at 13 U.S. sites.ResultsBetween February 2015 and December 2017, 31 patients were enrolled (median age 74.5 years [interquartile range (IQR): 71.3 to 81.0 years], 71% women, median Society of Thoracic Surgeons score 6.3% [IQR: 5.0% to 8.8%], 87.1% in New York Heart Association functional class III or IV). Access was transatrial (48.4%), transseptal (48.4%), or transapical (3.2%). Technical success was 74.2%. Left ventricular outflow tract obstruction (LVOTO) with hemodynamic compromise occurred in 3 patients (transatrial, n = 1; transseptal, n = 1; transapical, n = 1). After LVOTO occurred in the first 2 patients, pre-emptive alcohol septal ablation was implemented to decrease risk in high-risk patients. No intraprocedural deaths or conversions to open heart surgery occurred during the index procedures. All-cause mortality at 30 days was 16.7% (transatrial, 21.4%; transseptal, 6.7%; transapical, 100% [n = 1]; p = 0.33) and at 1 year was 34.5% (transatrial, 38.5%; transseptal, 26.7%; p = 0.69). At 1-year follow-up, 83.3% of patients were in New York Heart Association functional class I or II, the median mean mitral valve gradient was 6.1 mm Hg (IQR: 5.6 to 7.1 mm Hg), and all patients had ≤1+ mitral regurgitation.ConclusionsAt 1 year, ViMAC was associated with symptom improvement and stable transcatheter heart valve performance. Pre-emptive alcohol septal ablation may prevent transcatheter mitral valve replacement–induced LVOTO in patients at risk. Thirty-day mortality of patients treated via transseptal access was lower than predicted by the Society of Thoracic Surgeons score. Further studies are needed to evaluate safety and efficacy of ViMAC.     

Prognostic Links Between OCT-Delineated Coronary Morphologies and Coronary Functional Abnormalities in Patients With INOCA

ObjectivesWhether there are prognostic links between coronary morphologies and coronary functional abnormalities was examined in ischemia and nonobstructive coronary artery disease (INOCA) patients.BackgroundAlthough INOCA has attracted much attention, little is known about the prognostic impact of coronary morphologies in this disorder.MethodsA total of 329 consecutive INOCA patients were enrolled and underwent spasm provocation testing combined with lactate sampling for diagnosis of epicardial and microvascular spasm (MVS). On the basis of the functional tests, the patients were classified into 4 groups: a control group without epicardial spasm or MVS (n = 32), MVS alone (n = 51), diffuse spasm in ≥2 coronary segments (n = 204), and focal spasm in 1 segment (n = 42). In this population, optical coherence tomography imaging of the left anterior descending coronary artery was performed for evaluation of adventitial vasa vasorum (AVV) and intraplaque neovessels (IPN). Index of microcirculatory resistance was also measured.ResultsMVS frequently coexisted with diffuse (70%) and focal spasm (68%) with a good correlation between AVV and index of microcirculatory resistance (R = 0.353; p = 0.022). For a median follow-up of 1,043 days, focal spasm showed the worst prognosis (log rank p = 0.005), for which IPN was a significant prognostic factor. By contrast, diffuse spasm showed the greatest AVV with an intermediate prognosis. The prognostic value of INOCA was significantly enhanced by adding AVV and IPN to the physiological indices (area under the curve = 0.88 vs. 0.76; p = 0.048).ConclusionsThese results provide the first evidence that there are important prognostic links between coronary morphologies (evaluated by optical coherence tomography) and coronary functional abnormalities in patients with INOCA, indicating the importance of both evaluations in this population.     

Lung Ultrasound and Pulmonary Congestion During Stress Echocardiography

ObjectivesThe purpose of this study was to assess the functional and prognostic correlates of B-lines during stress echocardiography (SE).BackgroundB-profile detected by lung ultrasound (LUS) is a sign of pulmonary congestion during SE.MethodsThe authors prospectively performed transthoracic echocardiography (TTE) and LUS in 2,145 patients referred for exercise (n = 1,012), vasodilator (n = 1,054), or dobutamine (n = 79) SE in 11 certified centers. B-lines were evaluated in a 4-site simplified scan (each site scored from 0: A-lines to 10: white lung for coalescing B-lines). During stress the following were also analyzed: stress-induced new regional wall motion abnormalities in 2 contiguous segments; reduced left ventricular contractile reserve (peak/rest based on force, ≤2.0 for exercise and dobutamine, ≤1.1 for vasodilators); and abnormal coronary flow velocity reserve ≤2.0, assessed by pulsed-wave Doppler sampling in left anterior descending coronary artery and abnormal heart rate reserve (peak/rest heart rate) ≤1.80 for exercise and dobutamine (≤1.22 for vasodilators). All patients completed follow-up.ResultsAccording to B-lines at peak stress patients were divided into 4 different groups: group I, absence of stress B-lines (score: 0 to 1; n = 1,389; 64.7%); group II, mild B-lines (score: 2 to 4; n = 428; 20%); group III, moderate B-lines (score: 5 to 9; n = 209; 9.7%) and group IV, severe B-lines (score: ≥10; n = 119; 5.4%). During median follow-up of 15.2 months (interquartile range: 12 to 20 months) there were 38 deaths and 28 nonfatal myocardial infarctions in 64 patients. At multivariable analysis, severe stress B-lines (hazard ratio [HR]: 3.544; 95% confidence interval [CI]: 1.466 to 8.687; p = 0.006), abnormal heart rate reserve (HR: 2.276; 95% CI: 1.215 to 4.262; p = 0.010), abnormal coronary flow velocity reserve (HR: 2.178; 95% CI: 1.059 to 4.479; p = 0.034), and age (HR: 1.031; 95% CI: 1.002 to 1.062; p = 0.037) were independent predictors of death and nonfatal myocardial infarction.ConclusionsSevere stress B-lines predict death and nonfatal myocardial infarction. (Stress Echo 2020–The International Stress Echo Study [SE2020]; NCT03049995)     

Slow low-dose oral immunotherapy: Threshold and immunological change

BackgroundWe examined the feasibility, efficacy and safety of slow low-dose oral immunotherapy (SLOIT) for egg, milk, wheat allergies, with accepted severity-stratified initial and maintenance doses.MethodsChildren with food allergies defined by low-dose oral food challenges (LD-OFCs) to hen's egg (cumulative protein dose up to 983 mg, n = 133), cow's milk (287 mg, n = 50), and wheat (226 mg, n = 45) were recruited. Participants were divided into two groups [SLOIT and control (complete avoidance]) based on their preferences. Participants who selected SLOIT were instructed to take the safe dose daily, with monthly increases, aiming to increase the dose by 10 times in one year. The primary outcome was the proportion of participants who passed the LD-OFCs following 1 year of therapy.ResultsThe participants in SLOIT group ingested their antigen 92.9% of the therapy's day on average. The proportion of participants who passed LD-OFCs was 35.9% (61/170) in the SLOIT group and 8.7% (4/46) in the control group (P < .001); no large differences were observed among allergens. Among the subjects who failed LD-OFCs, the median change in the total dose in the LD-OFC was 235% (interquartile range: 100%–512%) in the SLOIT group and 100% (42%–235%) in the control group (P < .001). Provoked allergic symptoms were observed in only 0.58% (280/48,486) per programmed intake and approximately 50% of the SLOIT group did not experience any obvious allergic symptoms throughout therapy.ConclusionsSLOIT showed significant feasibility, efficacy and safety, providing a promising option to manage patients with severe food allergies.     

Transcatheter Treatment of Residual Significant Mitral Regurgitation Following TAVR: A Multicenter Registry

ObjectivesThe aim of this study was to describe baseline characteristics, and periprocedural and mid-term outcomes of patients undergoing transcatheter mitral valve interventions post-transcatheter aortic valve replacement (TAVR) and examine their clinical benefit.BackgroundThe optimal management of residual mitral regurgitation (MR) post-TAVR is challenging.MethodsThis was an international registry of 23 TAVR centers.ResultsIn total, 106 of 24,178 patients (0.43%) underwent mitral interventions post-TAVR (100 staged, 6 concomitant), most commonly percutaneous edge-to-edge mitral valve repair (PMVR). The median interval post-TAVR was 164 days. Mean age was 79.5 ± 7.2 years, MR was >moderate in 97.2%, technical success was 99.1%, and 30-day device success rate was 88.7%. There were 18 periprocedural complications (16.9%) including 4 deaths. During a median follow-up of 464 days, the cumulative risk for 3-year mortality was 29.0%. MR grade and New York Heart Association (NYHA) functional class improved dramatically; at 1 year, MR was moderate or less in 90.9% of patients (mild or less in 69.1%), and 85.9% of patients were in NYHA functional class I/II. Staged PMVR was associated with lower mortality versus medical treatment (57.5% vs. 30.8%) in a propensity-matched cohort (n = 156), but this was not statistically significant (hazard ratio: 1.75; p = 0.05).ConclusionsFor patients who continue to have significant MR, remain symptomatic post-TAVR, and are anatomically suitable for transcatheter interventions, these interventions are feasible, safe, and associated with significant improvement in MR grade and NYHA functional class. These results apply mainly to PMVR. A staged PMVR strategy was associated with markedly lower mortality, but this was not statistically significant. (Transcatheter Treatment for Combined Aortic and Mitral Valve Disease. The Aortic+Mitral TRAnsCatheter Valve Registry [AMTRAC]; NCT04031274)     

Lifetime risk of cardiovascular disease and life expectancy with and without cardiovascular disease according to changes in metabolic syndrome status

Background and aimsThe relationship between dynamic changes in metabolic syndrome (MetS) status and lifetime risk of cardiovascular disease (CVD) has not been reliably quantified. This study aimed to estimate lifetime risk of CVD and life expectancy with and without CVD according to dynamic MetS status.Methods and ResultsDynamic changes in MetS status were assessed: MetS-free, MetS-chronic, MetS-developed, and MetS-recovery groups. We used Modified Kaplan–Meier method to estimate lifetime risk and used multistate life table method to calculate life expectancy. Participants free of CVD at index ages 35 (n = 40 168), 45 (n = 33 569), and 55 (n = 18 546) years. At index age 35 years, we recorded 1341 CVD events during a median follow-up of 6.1 years. Lifetime risk of 33.9% (95% CI: 26.9%–41.0%) in MetS-recovery group was lower than that of 39.4% (95% CI: 36.1%–42.8%) in MetS-chronic group. Lifetime risk of 37.8% (95% CI: 30.6%–45.1%) in MetS-developed group was higher than that of 26.4% (95% CI: 22.7%–30.0%) in MetS-free group. At index age 35 years, life expectancy free of CVD for MetS-recovery group (44.1 years) was higher than that for MetS-chronic group (38.8 years). Life expectancy free of CVD for MetS-developed group (41.9 years) was lower than that for MetS-free group (46.7 years).ConclusionsRecovery from MetS was associated with decreased lifetime risk of CVD and a longer life expectancy free of CVD, whereas development of MetS was associated with increased lifetime risk of CVD and a shorter life expectancy free of CVD.     

Diagnostic and Prognostic Value of Ergonovine Echocardiography for Noninvasive Diagnosis of Coronary Vasospasm

ObjectivesThis study sought to obtain large-scale evidence supporting the clinical usefulness of ergonovine echocardiography.BackgroundThe role of noninvasive ergonovine provocation testing with echocardiographic monitoring of ventricular wall motion (ergonovine echocardiography) needs to be defined.MethodsClinical data of patients who underwent ergonovine echocardiography in 3 tertiary referral hospitals in South Korea were analyzed.ResultsErgonovine echocardiography was performed in 14,012 patients (mean age 52.8 ± 11.1 years; 6,213 [44.3%] women) after exclusion of significant coronary arterial stenosis by functional (treadmill or perfusion scan, n = 9,824) or anatomic test (invasive or computerized tomographic coronary angiography, n = 4,188). Premature termination developed in 0.4% (n = 51), and a positive result was observed in 2,144 patients (15.3%), with variable frequencies according to the diagnosis (acute coronary syndrome [38.2%], variant angina [31.8%], effort angina [14.9%], aborted sudden cardiac death [17.6%], syncope [9.9%]). There was no mortality or development of myocardial infarction during the test. During median follow-up of 11.4 (interquartile range: 7.2 to 15.8) years, death of any cause and cardiovascular death occurred in 494 and 143 patients, respectively. The 10-year overall (96.7 ± 0.2% vs. 91.5 ± 0.6%; p < 0.0001) and cardiovascular mortality–free (99.2 ± 0.1% vs. 96.7 ± 0.4%; p < 0.0001) survival rates were lower in patients with positive ergonovine echocardiography. Regarding patients with positive test results, the functional test group and the anatomic test group did not show a significant difference in the survival rates. After adjustment of age and male sex, a positive test was an independent risk factor associated with all-cause mortality (hazard ratio: 1.879, 95% confidence interval: 1.548 to 2.280; p < 0.001) and cardiovascular death (hazard ratio: 2.903, 95% confidence interval: 2.061 to 4.089; p < 0.001).ConclusionsErgonovine echocardiography for coronary vasospasm diagnosis could be safely performed even without angiographic documentation of fixed coronary stenosis depending on the clinical presentation, and provided important prognostic implication. Ergonovine echocardiography can replace the invasive spasm provocation testing, which has been overlooked unfairly.     

Reduction of Myocardial Infarction and All-Cause Mortality Associated to Statins in Patients Without Obstructive CAD

ObjectivesThe aim of this work was to evaluate the prognostic impact of statin therapy in symptomatic patients without obstructive CAD.BackgroundInformation on the prognostic impact of post–coronary computed tomographic angiography (CTA) statin use in patients with no or nonobstructive coronary artery disease (CAD) is sparse.MethodsPatients undergoing CTA with suspected CAD in western Denmark from 2008 to 2017 with <50% coronary stenoses were identified. Information on post-CTA use of statin therapy and cardiovascular events were obtained from national registries.ResultsThe study included 33,552 patients, median aged 56 years, 58% female, with no (n = 19,669) or nonobstructive (n = 13,883) CAD and a median follow-up of 3.5 years. The absolute risk of the combined end point of myocardial infarction (MI) or all-cause mortality was directly associated with the CAD burden with an event rate/1,000 patient-years of 4.13 (95% CI: 3.69-4.61) in no, 7.74 (95% CI: 6.88-8.71) in mild (coronary artery calcium score [CACS] 0-99), 13.72 (95% CI: 11.61-16.23) in moderate (CACS 100-399), and 32.47 (95% CI: 26.25-40.16) in severe (CACS ≥400) nonobstructive CAD. Statin therapy was associated with a multivariable adjusted HR for MI and death of 0.52 (95% CI: 0.36-0.75) in no, 0.44 (95% CI: 0.32-0.62) in mild, 0.51 (95% CI: 0.34-0.75) in moderate, and 0.52 (95% CI: 0.32-0.86) in severe nonobstructive CAD. The estimated numbers needed to treat to prevent the primary end point were 92 (95% CI: 61-182) in no, 36 (95% CI: 26-58) in mild, 24 (95% CI: 15-61) in moderate, and 13 (95% CI: 7-86) in severe nonobstructive CAD. Residual confounding may persist, but not to an extent explaining all of the observed risk reduction associated with statin treatment.ConclusionsThe risk of MI and all-cause mortality in patients without obstructive CAD is directly associated with the CAD burden. Statin therapy is associated with a reduction of MI and all-cause death across the spectrum of CAD, however, the absolute benefit of treatment is directionally proportional with the CAD burden.