Rapid Plaque Progression Is Independently Associated With Hyperglycemia and Low HDL Cholesterol in Patients With Stable Coronary Artery Disease: A PARADIGM Study.

BACKGROUND: We assessed whether combinations of cardiometabolic risk factors independently predict coronary plaque progression (PP) and major adverse cardiovascular events in patients with stable coronary artery disease. METHODS: Patients with known or suspected stable coronary artery disease (60.9±9.3 years, 55.4% male) undergoing serial coronary computed tomography angiographies (≥2 years apart), with clinical characterization and follow-up (N=1200), were analyzed from the PARADIGM study (Progression of Atherosclerotic Plaque Determined by Computed Tomographic Angiography Imaging). Plaque volumes measured in coronary segments (≥2 mm in diameter) were summed to provide whole heart plaque volume (mm3) and percent atheroma volume (plaque volume/vessel volume×100; %) per patient at baseline and follow-up. Rapid PP was defined as a percent atheroma volume increase of ≥1.0%/y. Major adverse cardiovascular events included nonfatal myocardial infarction, death, and unplanned coronary revascularization. RESULTS: In an interscan period of 3.2 years (interquartile range, 1.9), rapid PP occurred in 341 patients (28%). At multivariable analysis, the combination of cardiometabolic risk factors defined as metabolic syndrome predicted rapid PP (odds ratio, 1.51 [95% CI, 1.12-2.03]; P=0.007) together with older age, smoking habits, and baseline percent atheroma volume. Among single cardiometabolic variables, high fasting plasma glucose (diabetes or fasting plasma glucose >100 mg/dL) and low HDL-C (high-density lipoprotein cholesterol; <40 mg/dL in males and <50 mg/dL in females) were independently associated with rapid PP, in particular when combined (odds ratio, 2.37 [95% CI, 1.56-3.61]; P<0.001). In a follow-up of 8.23 years (interquartile range, 5.92-9.53), major adverse cardiovascular events occurred in 201 patients (17%). At multivariable Cox analysis, the combination of high fasting plasma glucose with high systemic blood pressure (treated hypertension or systemic blood pressure >130/85 mm Hg) was an independent predictor of events (hazard ratio, 1.79 [95% CI, 1.10-2.90]; P=0.018) together with family history, baseline percent atheroma volume, and rapid PP. CONCLUSIONS: In patients with stable coronary artery disease, the combination of hyperglycemia with low HDL-C is associated with rapid PP independently of other risk factors, baseline plaque burden, and treatment. The combination of hyperglycemia with high systemic blood pressure independently predicts the worse outcome beyond PP. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02803411.

Exercise Pulmonary Hypertension in Heart Valve Disease.

The optimal management of heart valve disease (HVD) is still debated and many studies are underway to identify the best time to refer patients for the most appropriate treatment strategy (either conservative, surgical or transcatheter interventions). Exercise pulmonary hypertension (PH) can be detected during exercise stress echocardiography (ESE) and has been demonstrated to have an important prognostic role in HVD, by predicting symptoms and mortality. This review article aims to provide an overview on the prognostic role of exercise PH in valvulopathies, and its possible role in the diagnostic-therapeutic algorithm for the management of HVD.

Subclinical hypothyroidism predicts outcome in heart failure: insights from the T.O.S.CA. registry.

Subclinical hypothyroidism (SH), defined as increased serum thyroid-stimulating hormone (TSH) with normal free T4 (fT4) levels, is frequently observed in the general population. Prevalence ranges from 0.6% to 1.8% in the adult population, depending on age, sex, and iodine intake. Several studies reported a worse prognosis in patients with heart failure with reduced ejection fraction (HFrEF) and SH, but they considered heterogeneous populations suffering mainly from severe SH. Aim of this study was to evaluate if SH was independently associated with the occurrence of cardiovascular death considering 30 months of follow-up. 277 HFrEF patients enrolled in the prospective, multicenter, observational T.O.S.CA. (Terapia Ormonale Scompenso CArdiaco) registry, were included in this analysis. Patients were divided into two groups according to the presence of SH (serum TSH levels > 4.5 mIU/L with normal fT4 levels). Data regarding clinical status, echocardiography, and survival were analyzed. Twenty-three patients displayed SH (87% mild vs 13% severe), while 254 were euthyroid. No differences were found in terms of age, sex, HF etiology, and left ventricular ejection fraction. When compared with the euthyroid group, SH patients showed higher TSH levels (7.7 ± 4.1 vs 1.6 ± 0.9, p < 0.001), as expected, with comparable levels of fT4 (1.3 ± 0.3 vs 1.3 ± 0.3, p = NS). When corrected for established predictors of poor outcome in HF, the presence of SH resulted to be an independent predictor of cardiovascular mortality (HR: 2.96; 5-95% CI:1.13-7.74; p = 0.03). Since thyroid tests are widely available and inexpensive, they should be performed in HF patients to detect subclinical disorders, evaluate replacement therapy, and improve prognosis.

Photon-Counting Computed Tomography in Atherosclerotic Plaque Characterization.

Atherosclerotic plaque buildup in the coronary and carotid arteries is pivotal in the onset of acute myocardial infarctions or cerebrovascular events, leading to heightened levels of illness and death. Atherosclerosis is a complex and multistep disease, beginning with the deposition of low-density lipoproteins in the arterial intima and culminating in plaque rupture. Modern technology favors non-invasive imaging techniques to assess atherosclerotic plaque and offer insights beyond mere artery stenosis. Among these, computed tomography stands out for its widespread clinical adoption and is prized for its speed and accessibility. Nonetheless, some limitations persist. The introduction of photon-counting computed tomography (PCCT), with its multi-energy capabilities, enhanced spatial resolution, and superior soft tissue contrast with minimal electronic noise, brings significant advantages to carotid and coronary artery imaging, enabling a more comprehensive examination of atherosclerotic plaque composition. This narrative review aims to provide a comprehensive overview of the main concepts related to PCCT. Additionally, we aim to explore the existing literature on the clinical application of PCCT in assessing atherosclerotic plaque. Finally, we will examine the advantages and limitations of this recently introduced technology.

Diagnostic accuracy of the aortic dissection detection risk score alone or with D-dimer for acute aortic syndromes: Systematic review and meta-analysis.

OBJECTIVES: To evaluate the diagnostic accuracy of the aortic dissection detection risk score (ADD-RS) used alone or in combination with D-dimer for detecting acute aortic syndrome (AAS) in patients presenting with symptoms suggestive of AAS. METHODS: We searched MEDLINE, EMBASE, and the Cochrane Library from inception to February 2024. Additionally, the reference lists of included studies and other systematic reviews were thoroughly searched. All diagnostic accuracy studies that assessed the use of ADD-RS alone or with D-Dimer for diagnosing AAS compared with a reference standard test (e.g. computer tomographic angiography (CTA), ECG-gated CTA, echocardiography, magnetic resonance angiography, operation, or autopsy) were included. Two reviewers independently selected and extracted data. Risk of bias was appraised using QUADAS-2 tool. Data were synthesised using hierarchical meta-analysis models. RESULTS: We selected 13 studies from the 2017 citations identified, including six studies evaluating combinations of ADD-RS alongside D-dimer>500ng/L. Summary sensitivities and specificities (95% credible interval) were: ADD-RS>0 94.6% (90%, 97.5%) and 34.7% (20.7%, 51.2%), ADD-RS>1 43.4% (31.2%, 57.1%) and 89.3% (80.4%, 94.8%); ADD RS>0 or D-Dimer>500ng/L 99.8% (98.7%, 100%) and 21.8% (12.1%, 32.6%); ADD RS>1 or D-Dimer>500ng/L 98.3% (94.9%, 99.5%) and 51.4% (38.7%, 64.1%); ADD RS>1 or ADD RS = 1 with D-dimer>500ng/L 93.1% (87.1%, 96.3%) and 67.1% (54.4%, 77.7%). CONCLUSIONS: Combinations of ADD-RS and D-dimer can be used to select patients with suspected AAS for imaging with a range of trade-offs between sensitivity (93.1% to 99.8%) and specificity (21.8% to 67.1%).

Application of the 2016 ASE-EACVI Criteria for the Assessment of Diastolic Function in Arterial Hypertension.

INTRODUCTION: No data are available on the diagnostic algorithms recommended by guidelines for the assessment of diastolic dysfunction (DD) in patients with arterial hypertension. AIM: To fill this gap, we evaluated diastolic function in hypertensive patients with and without LVH matched with healthy subjects by applying 2016 American Society of Echocardiography-European Association of Cardiovascular Imaging Guidelines for the evaluation of LV diastolic function. METHODS: 717 healthy and hypertensives with normal LV ejection fraction and with and without LV hypertrophy (LVH), matched 1:1:1 from two prospective registries, represented the study population. RESULTS: By applying algorithm A, indeterminate pattern was found in 0.4% of healthy, in 6.3% of hypertensives without LVH, and in 21% with LVH (overall p < 0.05 vs. healthy). DD was absent in healthy, however present in 2 and 8% of hypertensives without and with LVH (p = 0.06 and p = 0.001 vs. healthy, respectively). By applying algorithm B, no cases of indeterminate pattern were found. DD was observed in 2.9% of healthy, 7 and 10.5% of hypertensives without and with LVH (p < 0.05 vs. healthy). CONCLUSIONS: The use of algorithm A should be limited only to truly normal subjects, whereas algorithm B should be applied to all patients with hypertension, even without comorbidities and irrespective of LVH.

Effect of beta-blockers and angiotensin receptor blockers in reducing the aortic growth rate in children with bicuspid aortic valve-related aortopathy.

AIMS: The aim of this study is to evaluate the effect of beta-blockers and angiotensin receptor blockers in reducing the aortic growth rate in children with bicuspid aortic valve (BAV)-related aortopathy and ascending phenotype. METHODS: Consecutive paediatric patients (≤16 years) with BAV and ascending aorta (AsAo) dilation (z-score > 3) were enrolled in this observational retrospective cohort study. Patients receiving prophylactic treatment with either atenolol (0.5 to 1.0 mg/kg/daily) or losartan (0.7 to 1.4 mg/kg/daily) were compared with those who did not receive medical prophylaxis (control group). The primary outcome of interest was the annual rate of change in maximal AsAo diameter z-score in the treatment and control groups. RESULTS: From a cohort of 1005 patients, 120 (mean age 11.3 ± 4.5 years, 82% males) fulfilled the inclusion criteria and were included in the study. Patients in the treatment and control group had similar age, sex, family history of BAV, BAV morphology, and baseline AsAo diameter. During a median follow-up of 7.1 years (interquartile range 3.8-10.2), no differences were observed in the annual growth rate of aortic diameter z-score between patients on treatment and controls. The prevalence of aortic diameter progression was similar in the treatment and control groups, and treatment with atenolol or losartan was not associated with a lower rate of aortic disease progression. CONCLUSIONS: The findings revealed no significant difference in the annual aortic growth rate between treated and untreated patients. Larger cohort studies or, ideally, randomized clinical controlled trials are needed to validate these findings.

Spectral Photon-Counting Computed Tomography: Technical Principles and Applications in the Assessment of Cardiovascular Diseases.

Spectral Photon-Counting Computed Tomography (SPCCT) represents a groundbreaking advancement in X-ray imaging technology. The core innovation of SPCCT lies in its photon-counting detectors, which can count the exact number of incoming x-ray photons and individually measure their energy. The first part of this review summarizes the key elements of SPCCT technology, such as energy binning, energy weighting, and material decomposition. Its energy-discriminating ability represents the key to the increase in the contrast between different tissues, the elimination of the electronic noise, and the correction of beam-hardening artifacts. Material decomposition provides valuable insights into specific elements' composition, concentration, and distribution. The capability of SPCCT to operate in three or more energy regimes allows for the differentiation of several contrast agents, facilitating quantitative assessments of elements with specific energy thresholds within the diagnostic energy range. The second part of this review provides a brief overview of the applications of SPCCT in the assessment of various cardiovascular disease processes. SPCCT can support the study of myocardial blood perfusion and enable enhanced tissue characterization and the identification of contrast agents, in a manner that was previously unattainable.

Management of Systemic Inflammatory Response Syndrome After Cardiovascular Interventions. Diagnostic, Prognostic, and Therapeutic Implications.

A substantial number of patients may experience systemic inflammatory response syndrome (SIRS) and related adverse events after transcatheter aortic valve implantation and endovascular aortic aneurysm repair. Although a clear etiology has not been established, endothelial disruption and tissue-ischemic response secondary to the foreign material may represent the trigger events. A latency period (0 to 48 hours) may occur between the initial injury and onset of symptoms mirroring an initial local response followed by a systemic response. Clinical presentation can be mild or severe depending on external triggers and characteristics of the patient. Diagnosis is challenging because it simulates an infection, but lack of response to antibiotics, negative cultures are supportive of SIRS. Increased in-hospital stay, readmissions, major cardiovascular events, and reduced durability of the device used are the main complications. Treatment includes non-steroidal anti-inflammatory drugs or corticosteroids. In conclusion, further studies are warranted to fully explore pathophysiologic mechanisms underpinning SIRS and the possibility of enhancing device material immune compatibility to reduce the inflammatory reaction of the host tissue.

Aortopathy and aortic valve surgery in patients with bicuspid aortic valve with and without raphe.

AIM: To evaluate the association between raphe in bicuspid aortic valve (BAV) patients and valve dysfunction, aortopathy and aortic valve surgery in the REBECCA registry [REgistro della valvola aortica Bicuspide della Società Italiana di ECocardiografia e CArdiovascular Imaging (SIECVI)]. METHODS: Prevalence of aortic valve dysfunction and aortopathy was investigated in BAV patients with and without raphe. Aortic valve dysfunction (regurgitation or stenosis) was categorized as mild, moderate and severe. Aortopathy was defined as annulus ≥14 mm/m2; root ≥20 mm/m2; sinotubular junction ≥16 mm/m2; ascending aorta ≥17 mm/m2, and classified in Type A, isolated ascending aorta dilatation; Type B, aortic root and ascending aorta dilatation; and Type C, isolated aortic root dilatation. RESULTS: Overall, 695 patients with BAV were enrolled; 520 (74.8%) with raphe and 175 (25.2%) without raphe. BAV patients with raphe presented more frequently with moderate or severe aortic stenosis than BAV patients without raphe (183 [35.2%] vs 34 [19.4%], p < 0.001). A higher prevalence of aortopathy, particularly Type B, was observed in patients with vs without raphe. At multivariable analysis, raphe was a predictor of aortic valve surgery at three-year follow-up (odds ratio 2.19, 95% confidence interval 1.08-4.44, p < 0.001). CONCLUSIONS: Patients with BAV and raphe have a higher prevalence of significant aortic stenosis, aortopathy, especially Type B, and a higher risk of undergoing aortic valve surgery at three-year follow-up.

Right heart failure as a cause of pulmonary congestion in pulmonary arterial hypertension.

AIMS: Recent studies have shown that lung ultrasound-assessed pulmonary congestion is worse in heart failure when pulmonary vascular resistance (PVR) is increased, suggesting a paradoxical relationship between right heart failure and increased lung water content. Accordingly, we wondered if lung ultrasound would reveal otherwise clinically silent pulmonary congestion in patients with pulmonary arterial hypertension (PAH). METHODS AND RESULTS: All patients referred for suspicion of PAH in a tertiary centre from January 2020 to December 2022 underwent a complete diagnostic work-up including echocardiography, lung ultrasound and right heart catheterization. Pulmonary congestion was identified by lung ultrasound B-lines using an 8-site scan. The study enrolled 102 patients with idiopathic PAH (mean age 53 ± 13 years; 71% female). World Health Organization functional classes I, II, and III were found in 2%, 52%, and 46% of them, respectively. N-terminal pro-brain natriuretic peptide (NT-proBNP) was 377 pg/ml (interquartile range [IQR] 218-906). B-lines were identified in 77 out of 102 patients (75%), with a median of 3 [IQR 1-5]. At univariable analysis, B-lines were positively correlated with male sex, age, NT-proBNP, systolic pulmonary artery pressure (sPAP), right atrial pressure (RAP), PVR, left ventricular end-diastolic volume and tricuspid annular plane systolic excursion (TAPSE), and negatively with cardiac output and stroke volume. At multivariable analysis, RAP (p < 0.001), TAPSE/sPAP (p = 0.001), and NT-proBNP (p = 0.04) were independent predictors of B-lines. CONCLUSION: Lung ultrasound commonly discloses pulmonary congestion in PAH. This finding is related to right ventricular to pulmonary artery uncoupling, and may tentatively be explained by increased central venous pressure impeding lymphatic outflow.