Reduction of Coronary Flow Velocity Reserve as the Main Driver of Prognostically Beneficial Coronary Revascularization.

BACKGROUND: Regional wall motion abnormality (RWMA) can be absent during stress echocardiography (SE) in patients with chronic coronary syndromes (CCS) and angiographically significant coronary artery disease (CAD) despite a reduction of coronary flow velocity reserve (CFVR). OBJECTIVES: To assess the value of a physiology-driven approach,based on CFVR, to coronary revascularization in patients with physiologically and anatomically significant disease of the left anterior descending (LAD) coronary artery. METHODS: In a 3-center, observational study with retrospective analysis of prospectively acquired data, 749 patients with CCS, CFVR of the LAD <2.0, and ≥50% diameter stenosis of the LAD were enrolled. All patients were evaluated with dipyridamole (0.84 mg/kg in 6') SE. Patients were followed for 6.4±4.5 years for the outcome of all-cause death. RESULTS: Inducible RWMA was present in 295 patients (39%). CFVR was lower in patients with inducible RWMA compared to those without (1.51±0.28 vs 1.65±0.25; p<00001). Coronary revascularization was performed in 514 (69%) patients (388 with percutaneous coronary intervention, 126 with coronary artery bypass surgery). Of them, 226 exhibited inducible RWMA and 288 isolated reduction of CFVR. During the follow-up, 185 (25%) deaths occurred. The 10-year survival in the entire study population was 70%. The survival at 10 years was markedly lower in conservatively treated patients compared to invasively treated patients (53 vs 76%; p<0.0001), with no significant difference between those with solitary reduction of CFVR and reduction of CFVR accompanied by concurrent inducible RWMA. Propensity Score weighted all-cause mortality risk resulted to be significantly higher for conservative than for invasive strategy (Propensity Score adjusted: HR 2.12, 95% CI 1.51-2.96; p<0.0001). CONCLUSIONS: In patients with CCS and physiologically and anatomically significant LAD disease, coronary revascularization driven by a reduction in CFVR is accompanied by a prognostic benefit independently of the presence of inducible RWMA.

Long-term outcomes comparison of mitral valve repair or replacement for secondary mitral valve regurgitation. An updated systematic review and reconstructed time-to-event study-level meta-analysis.

BACKGROUND AND AIM: The ideal surgical intervention for secondary mitral regurgitation (SMR), a disease of the left ventricle not the mitral valve itself, is still debated. We performed an updated systematic review and study-level meta-analysis investigating mitral valve repair (MVr) versus mitral valve replacement (MVR) for adult patients with SMR, with or without coronary artery disease (CAD). METHODS: PubMed, CENTRAL and EMBASE were searched for studies comparing MVr versus MVR. Randomized trial or observational studies were considered eligible. Primary endpoint was long-term mortality for any cause. Kaplan-Meier survival curves were reconstructed and compared with Cox linear regression. Landmark analysis and time-varying hazard ratio (HR) were analyzed. Sensitivity analyses included meta-regression and separate sub-analysis. A random effects model was used. RESULTS: Twenty-three studies (MVr=3,727 and MVR=2,839) were included. One study was a randomized trial, and 19 studies were adjusted. The mean weighted follow-up was 3.7±2.8 years. MVR was associated with significative greater late mortality (HR=1.26; 95 % CI, 1.14-1.39; P<0.0001) at 10-year follow-up. There was a time-varying trend showing an increased risk of mortality in the first 2 years after MVR (HR=1.38; 95 % CI, 1.21-1.56; P<0.0001), after which this difference dissipated (HR=0.94; 95 % CI, 0.81-1.09; P=0.41). Separate sub-analyses showed comparable long-term mortality in patients with concomitant coronary surgery ≥90 %, left ventricle ejection fraction ≤40 %, and sub-valvular apparatus preservation rate of 100 %. CONCLUSIONS: Compared to repair, MVR is associated with higher probability of mortality in the first 2 years following surgery, after which the two procedures showed comparable late mortality rate.

Coronary inflammation on chest computed tomography and COVID-19 mortality.

OBJECTIVES: The main factors associated with coronavirus disease-19 (COVID-19) mortality are age, comorbidities, pattern of inflammatory response, and SARS-CoV-2 lineage involved in infection. However, the clinical course of the disease is extremely heterogeneous, and reliable biomarkers predicting adverse prognosis are lacking. Our aim was to elucidate the prognostic role of a novel marker of coronary artery disease inflammation, peri-coronary adipose tissue attenuation (PCAT), available from high-resolution chest computed tomography (HRCT) in COVID-19 patients with severe disease requiring hospitalization. METHODS: Two distinct groups of patients were admitted to Parma University Hospital in Italy with COVID-19 in March 2020 and March 2021 (first- and third-wave peaks of the COVID-19 pandemic in Italy, with the prevalence of wild-type and B.1.1.7 SARS-CoV-2 lineage, respectively) were retrospectively enrolled. The primary endpoint was in-hospital mortality. Demographic, clinical, laboratory, HRCT data, and coronary artery HRCT features (coronary calcium score and PCAT attenuation) were collected to show which variables were associated with mortality. RESULTS: Among the 769 patients enrolled, 555 (72%) were discharged alive, and 214 (28%) died. In multivariable logistic regression analysis age (p < 0.001), number of chronic illnesses (p < 0.001), smoking habit (p = 0.006), P/F ratio (p = 0.001), platelet count (p = 0.002), blood creatinine (p < 0.001), non-invasive mechanical ventilation (p < 0.001), HRCT visual score (p < 0.001), and PCAT (p < 0.001), but not the calcium score, were independently associated with in-hospital mortality. CONCLUSION: Coronary inflammation, measured with PCAT on non-triggered HRCT, appeared to be independently associated with higher mortality in patients with severe COVID-19, while the pre-existent coronary atherosclerotic burden was not associated with adverse outcomes after adjustment for covariates. CLINICAL RELEVANCE STATEMENT: The current study demonstrates that a relatively simple measurement, peri-coronary adipose tissue attenuation (PCAT), available ex-post from standard high-resolution computed tomography, is strongly and independently associated with in-hospital mortality. KEY POINTS: • Coronary inflammation can be measured by the attenuation of peri-coronary adipose tissue (PCAT) on high-resolution CT (HRCT) without contrast media. • PCAT is strongly and independently associated with in-hospital mortality in SARS-CoV-2 patients. • PCAT might be considered an independent prognostic marker in COVID-19 patients if confirmed in other studies.

Very Long-term Outcome of Bilateral Internal Thoracic Artery in Diabetic Patients: A Systematic Review and Reconstructed Time-To-Event Meta-analysis.

The benefits of single (SITA) and bilateral internal thoracic arteries (BITA) in diabetics undergoing coronary bypass grafting (CABG) are conflicting. We undertook a study-level meta-analysis to compare early and long-term outcomes of both CABG configurations. PubMed, CENTRAL, and EMBASE were searched for studies comparing BITA versus SITA for isolated CABG surgery in diabetics. Randomized trials or observational studies were considered eligible for the analysis. Kaplan-Meier curves of long-term survival were reconstructed and compared with Cox linear regression; incidence rate ratios (IRR) with 95% confidence intervals (CI) for long-term survival were calculated. Landmark analysis and time-varying hazard ratio (HR) were analyzed. Odds ratios (OR) were extracted for early mortality, postoperative stroke, deep sternal wound infection (DSWI), and myocardial infarction (MI). A random effects meta-analysis was performed. Sensitivity analyses included leave-one-out-analyses and meta-regression. Thirteen studies (7332 patients) were included. Overall, at 20-year follow-up, BITA was associated with higher survival (HR = 0.77; 95% CI, 0.71-0.84; P < 0.0001). Time-varying HR and landmark analysis reported BITA was associated with a higher rate of 10-year survival (HR = 0.75, 95% CI 0.68-0.82, P < 0.0001), while from 10 to 20-year follow-up no difference was revealed (HR = 0.99, 95% CI 0.82-1.19, P = 0.93). There was no increase in early mortality, postoperative MI, stroke, or DSWI between the groups. At meta-regression, the higher the age, the higher the long-term overall survival in patients with BITA. In diabetics, the BITA approach is associated with improved 10-year survival with no increase in early mortality, MI, stroke, or DSWI. In the 10-20-year timeframe, BITA and SITA showed comparable survival.

Results beyond 5-years of surgery or percutaneous approach in severe coronary disease. Reconstructed time-to-event meta-analysis of randomized trials.

INTRODUCTION AND OBJECTIVES: There is controversy about the optimal revascularization strategy in severe coronary artery disease (CAD), including left main disease and/or multivessel disease. Several meta-analyses have analyzed the results at 5-year follow-up but there are no results after the fifth year. We conducted a systematic review and meta-analysis of randomized clinical trials, comparing results after the fifth year, between coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) using drug-eluting stents in patients with severe CAD. METHODS: We analyzed all clinical trials between January 2010 and January 2023. The primary endpoint was all-cause mortality. The databases of the original articles were reconstructed from Kaplan-Meier curves, simulating an individual-level meta-analysis. Comparisons were made at certain cutoff points (5 and 10 years). The 10-year restricted median survival time difference between CABG and PCI was calculated. The random effects model and the DerSimonian-Laird method were applied. RESULTS: The meta-analysis included 5180 patients. During the 10-year follow-up, PCI showed a higher overall incidence of all-cause mortality (HR, 1.19; 95%CI, 1.04-1.32; P=.008)]. PCI showed an increased risk of all-cause mortality within 5 years (HR, 1.2; 95%CI, 1.06-1.53; P=.008), while no differences in the 5-10-year period were revealed (HR, 1.03; 95%CI, 0.84-1.26; P=.76). Life expectancy of CABG patients was slightly higher than that of PCI patients (2.4 months more). CONCLUSIONS: In patients with severe CAD, including left main disease and/or multivessel disease, there was higher a incidence of all-cause mortality after PCI compared with CABG at 10 years of follow-up. Specifically, PCI has higher mortality during the first 5 years and comparable risk beyond 5 years.

Echocardiographic Markers in the Diagnosis of Cardiac Masses.

BACKGROUND: The echocardiographic parameters required for a comprehensive assessment of cardiac masses (CMs) are still largely unknown. The aim of this study was to identify and integrate the echocardiographic features of CMs that can accurately predict malignancy. METHODS: An observational cohort study was conducted among 286 consecutive patients who underwent standard echocardiographic assessment for suspected CM at Bologna University Hospital between 2004 and 2022. A definitive diagnosis was achieved by histologic examination or, in the case of cardiac thrombi, with radiologic evidence of thrombus resolution after appropriate anticoagulant treatment. Logistic and multivariable regression analysis was performed to confirm the ability of six echocardiographic parameters to discriminate malignant from benign masses. The unweighted count of these parameters was used as a numeric score, ranging from 0 to 6, with a cutoff of ≥3 balancing sensitivity and specificity with respect to the histologic diagnosis of malignancy. Classification tree analysis was used to determine the ability of echocardiographic parameters to discriminate subgroups of patients with differential risk for malignancy. RESULTS: Benign masses were more frequently pedunculated, mobile, and adherent to the interatrial septum (P < .001). Malignant masses showed a greater diameter and exhibited a higher frequency of irregular margins, an inhomogeneous appearance, sessile implantation, polylobate shape, and pericardial effusion (P < .001). Infiltration, moderate to severe pericardial effusion, nonleft localization, sessile implantation, polylobate shape, and inhomogeneity were confirmed to be independent predictors of malignancy in both univariate and multivariable models. The predictive ability of the unweighted score of ≥3 was very high (>0.90) and similar to that of the previously published weighted score. Classification tree analysis generated an algorithm in which infiltration was the best discriminator of malignancy, followed by nonleft localization and sessile implantation. The percentage correctly classified by classification tree analysis as malignant was 87.5%. Agreement between observer readings and CM histology ranged between 85.1% and 91.5%. The presence of at least three echocardiographic parameters was associated with lower survival. CONCLUSIONS: In the approach to CMs, some echocardiographic parameters can serve as markers to accurately predict malignancy, thereby informing the need for second-level investigations and minimizing the diagnostic delay in such a complex clinical scenario.

Sex-Related Differences in Long-Term Outcomes After Early-Onset Myocardial Infarction.

Importance: There is growing awareness of sex-related differences in cardiovascular risk profiles, but less is known about whether these extend to pre-menopausal females experiencing an early-onset myocardial infarction (MI), who may benefit from the protective effects of estrogen exposure. Methods: A nationwide study involving 125 Italian Coronary Care Units recruited 2,000 patients between 1998 and 2002 hospitalized for a type I myocardial infarction before the age of 45 years (male, n = 1,778 (88.9%). Patients were followed up for a median of 19.9 years (IQR 18.1-22.6). The primary composite endpoint was the occurrence of cardiovascular death, non-fatal myocardial re-infarction or non-fatal stroke, and the secondary endpoint of hospitalization for revascularisation by means of a percutaneous coronary intervention (PCI) or coronary artery bypass surgery (CABG). Results: ST-elevation MI was the most frequent presentation among both men and women (85.1 vs. 87.4%, p = ns), but the men had a greater baseline coronary atherosclerotic burden (median Duke Coronary Artery Disease Index: 48 vs. 23; median Syntax score 9 vs. 7; both p < 0.001). The primary composite endpoint occurred less frequently among women (25.7% vs. 37.0%; adjusted hazard ratio: 0.69, 95% CI 0.52-0.91; p = 0.01) despite being less likely to receive treatment with most secondary prevention medications during follow up. Conclusions: There are significant sex-related differences in baseline risk factors and outcomes among patients with early-onset MI: women present with a lower atherosclerotic disease burden and, although they are less frequently prescribed secondary prevention measures, experience better long-term outcomes. Trial Registration: 4272/98 Ospedale Niguarda, Ca' Granda 03/09/1998.

The early and long-term outcomes of coronary artery bypass grafting added to aortic valve replacement compared to isolated aortic valve replacement in elderly patients: a systematic review and meta-analysis.

In aged population, the early and long-term outcomes of coronary revascularization (CABG) added to surgical aortic valve replacement (SAVR) compared to isolated SAVR (i-SAVR) are conflicting. To address this limitation, a meta-analysis comparing the early and late outcomes of SAVR plus CABG with i-SAVR was performed. Electronic databases from January 2000 to November 2021 were screened. Studies reporting early-term and long-term comparison between the two treatments in patients over 75 years were analyzed. The primary endpoints were in-hospital/30-day mortality and overall long-term survival. The pooled odd ratio (OR) and hazard ratio (HR) with 95% confidence interval (CI) were calculated for in-early outcome and long-term survival, respectively. Random-effect model was used in all analyses. Forty-four retrospective observational studies reporting on 74,560 patients (i-SAVR = 36,062; SAVR + CABG = 38,498) were included for comparison. The pooled analysis revealed that i-SAVR was significantly associated with lower rate of early mortality compared to SAVR plus CABG (OR = 0.70, 95% CI 0.66-0.75; p < 0.0001) and with lower incidence of postoperative acute renal failure (OR = 0.65; 95% CI 0.50-0.91; p = 0.02), need for dialysis (OR = 0.65; 95% CI 0.50-0.86; p = 0.002) and prolonged mechanical ventilation (OR = 0.57; 95% CI 0.42-0.77; p < 0.0001). Twenty-two studies reported data of long-term follow-up. No differences were reported between the two groups in long-term survival (HR = 0.95; 95% CI 0.87-1.03; p = 0.23). CABG added to SAVR is associated with worse early outcomes in terms of early mortality, postoperative acute renal failure, and prolonged mechanical ventilation. Long-term survival was comparable between the two treatments.

When 3D echocardiography truly makes the difference: a case report of mitral annular ring dehiscence.

Real time 3D echocardiography has an established incremental diagnostic value over 2D imaging, especially during transesophageal evaluation of native and prosthetic heart valves. A 66 years old male patient, with an history of previous cardiac surgery for mitral annuloplasty and recurrent fever, came to the attention of our echo lab with an indication for transesophageal echocardiography after previous inconclusive transthoracic echocardiograms. Real time 3D echocardiography and 3D color doppler imaging resulted of outmost importance to clarify the presence of annular ring dehiscence, previously not well defined from 2D echocardiography imaging.

The Histopathological Correlate of Peri-Vascular Adipose Tissue Attenuation on Computed Tomography in Surgical Ascending Aorta Aneurysms: Is This a Measure of Tissue Inflammation?

On computed tomography (CT) imaging, a peri-vascular adipose tissue attenuation (pVAT) measure has been proposed as a non-invasive correlate of inflammation in the coronary artery vessels, and a single research group provided histopathological demonstration of this radiological/pathological correspondence. Our group has shown that patients with surgical-grade ascending aorta (AA) aneurysm display higher pVAT compared with patients with smaller aneurysms or normal AA. Based on histopathological studies on coronary arteries, we speculated that this correlation may be related to a non-otherwise specified aortic inflammatory process. However, since adipose tissue around the AA is often scant, and there are no histopathological studies confirming such hypothesized association between higher pVAT and inflammation around the AA, we cannot exclude that this pVAT change is secondary to different mechanisms, unrelated to the actual presence of peri-vascular inflammation. We performed a retrospective clinical/radiological/pathological study in 78 patients who underwent AA surgery with the aim to correlate pre-operatory pVAT on CT with histopathological findings from the surgical specimens. Histopathological review and immunohistochemistry were performed on the surgical aortic samples. The AA adventitial/periadventitial adipose tissue had higher pVAT by an increasing collagen fiber deposition, which progressively makes the fat hypotrophic and, in the late stages of this process, it replaces the normal soft tissue composition in this location. In the ascending aorta, pVAT on CT imaging is probably not a proxy for the presence of current vascular inflammation, although it may track changes involving the progressive substitution of perivascular adipose cells by higher-pVAT tissues, mainly fibrotic replacement.

Stress Echo 2030: The Novel ABCDE-(FGLPR) Protocol to Define the Future of Imaging.

With stress echo (SE) 2020 study, a new standard of practice in stress imaging was developed and disseminated: the ABCDE protocol for functional testing within and beyond CAD. ABCDE protocol was the fruit of SE 2020, and is the seed of SE 2030, which is articulated in 12 projects: 1-SE in coronary artery disease (SECAD); 2-SE in diastolic heart failure (SEDIA); 3-SE in hypertrophic cardiomyopathy (SEHCA); 4-SE post-chest radiotherapy and chemotherapy (SERA); 5-Artificial intelligence SE evaluation (AI-SEE); 6-Environmental stress echocardiography and air pollution (ESTER); 7-SE in repaired Tetralogy of Fallot (SETOF); 8-SE in post-COVID-19 (SECOV); 9: Recovery by stress echo of conventionally unfit donor good hearts (RESURGE); 10-SE for mitral ischemic regurgitation (SEMIR); 11-SE in valvular heart disease (SEVA); 12-SE for coronary vasospasm (SESPASM). The study aims to recruit in the next 5 years (2021-2025) ≥10,000 patients followed for ≥5 years (up to 2030) from ≥20 quality-controlled laboratories from ≥10 countries. In this COVID-19 era of sustainable health care delivery, SE2030 will provide the evidence to finally recommend SE as the optimal and versatile imaging modality for functional testing anywhere, any time, and in any patient.

Coronary Flow Velocity Reserve Reduction Is Associated with Cardiovascular, Cancer, and Noncancer, Noncardiovascular Mortality.

BACKGROUND: Coronary flow velocity reserve (CFVR) measured in the left anterior descending artery during high-dose vasodilator stress echocardiography interrogates both epicardial and microcirculatory coronary function and has been inversely associated with chronic inflammation and microvascular dysfunction, as well as with the presence of obstructive coronary artery disease. Microvascular dysfunction and chronic inflammation are common mechanisms of disease in cardiovascular (CV) and non-CV conditions. We aimed to assess whether CFVR is associated with all-cause death, but more specifically with CV, cancer, and non-CV and noncancer (NCVNC) mortality, independently and increasingly over other demographic, clinical, and echocardiography variables. METHODS: One thousand two patients who underwent stress echocardiography were followed for a median of 8.2 years, with clinical, regional wall motion abnormalities (RWMAs), and CFVR data. The independent prognostic value of RWMA and CFVR regarding CV, cancer, or NCVNC mortality was evaluated adjusting for clinical variables. A prespecified subgroup of subjects with no RWMA or revascularization procedures during follow-up was also analyzed (n = 752), to exclude most participants with possible coronary artery disease and remove such confounding from the assessment of the potential association of CFVR and mortality. RESULTS: A total of 161 patients (16%) died, 63 deaths being CV (39%), 52 from cancer (32%), and 46 (29%) from NCVNC causes. In comparison to CV mortality, cancer and NCVNC mortality were not associated with an ischemic RWMA at univariable analysis, while a CFVR < 2 was significantly associated with each category of cause-specific mortality. A CFVR < 2 or ≥2 separated a group of patients with 8-year 14.6% versus 1.2% CV mortality, 10.3% versus 0.4% cancer mortality, and 9.5% versus 1.5% NCVNC mortality. CONCLUSIONS: The reduction of CFVR is independently associated with CV, cancer, and NCVNC death in a population clinically referred for suspected/known coronary artery disease. CFVR can act as a marker or a mechanism preceding and predicting mortality from a wide variety of diseases.

Standard echocardiography versus very-low mechanical index contrast-imaging: left ventricle volumes and ejection fraction multi-reader variability and reference values in a subgroup with no risk factors or cardiac disease.

We retrospectively assessed the rest-phase images of 300 contrast stress- echocardiograms, during which very-low mechanical index (VLMI) imaging with ultrasound enhancing agents (UEAs) was routinely acquired in addition to greyscale echocardiography; intra- and inter-reader variability for left ventricle (LV) volumes and ejection fraction (LVEF) at rest was established in the overall cohort and normal values were calculated in the subset of subjects with no cardiac risk factors or cardiac disease and a normal stress-echocardiogram. Current recommendations for chamber quantification using echocardiography advise the use of UEAs in case of insufficient quality of endocardial visualization, but normal values for LV volumes and LVEF using UEAs have never been published using currently recommended VLMI method. Single-centre retrospective study, enrolling subjects referred to contrast stress- echocardiography for suspect coronary artery disease, including the acquisition of both standard 2D greyscale and bolus UEAs with VLMI, regardless of the image quality. This enables offline measurement of the LV volumes and LVEF for both greyscale and UEAs-VLMI images at rest in all subjects. Images were allocated to 3 readers in random order. Normal range for LV volumes and LVEF was also derived in a subset of apparently healthy subjects. In the 298 exams finally assessed, measurement variability among the three readers was lower with UEAs-VLMI, in particular for end-systolic volumes (intra-class correlation coefficient for concordance improved from 0.855 to 0.916, for LVEF from 0.68 to 0.783, p < 0.01), intra- observer variability reduced (Lin's correlation coefficient for LVEF from 0.747 to 0.857, p < 0.01). Normal mean indexed LV end-diastolic volume with UEAs-VLMI, compared to greyscale imaging, was + 14 ml/m2, while LVEF was + 5 to + 6% points. This is the largest study specifically addressing UEAs-VLMI imaging and comparing data with standard greyscale imaging; it demonstrates a reduction in measurement variability of LV volumes and LVEF. Normal reference values for VLMI ultrasound are reported for the first time in comparison with greyscale values.