Exercise Stress Echocardiography for Stable Coronary Artery Disease: Succumbed to the Modern Conceptual Revolution or Still Alive and Kicking?

The modern conceptual revolution in managing patients with stable coronary artery disease (CAD), based on improvement in preventive and pharmacological therapy, advocates coronary artery revascularization only for smaller group of patients with refractory angina, poor left ventricular systolic function, or high-risk coronary anatomy. Therefore, our conventional wisdom about stress testing must be questioned within this new and revolutionary paradigm. Exercise stress echocardiography (ESE) is still a well-known technique for assessing known or suspected stable CAD, it is safe, accessible, and well-tolerated, and there is an widespread evidence base. ESE has been remarkably resilient throughout years of innovation in noninvasive cardiology. Its value is not to be determined over the short portion of diagnostic accuracy but mainly through its prognostic value evident in a wide range of patient subsets. It is coming very close to the modern profile of a leading test that should include, in addition to an essential accettable diagnostic and prognostic accuracy, qualities of low cost, no radiation exposure, and minor environmental traces. In this review, we will discuss advantages, diagnostic accuracy, prognostic value in general and special populations, cost-effectiveness, and changes in referral patterns of ESE in the modern era.

Effects of Sacubitril/Valsartan on biomarkers of fibrosis and inflammation in patients with heart failure with reduced ejection fraction.

AIMS: To evaluate the circulating levels of remodeling biomarkers procollagen type 1 C-terminal propeptide (PICP), human cartilage glycoprotein-39 (YKL-40), plasma renin activity (PRA), aldosterone (Aldo) as well as clinical and echocardiographic parameters in patients with heart failure with reduced ejection fraction (HFrEF), before and after treatment with Sacubitril/Valsartan (S/V). METHODS AND RESULTS: A total of 26 consecutive patients with HFrEF on stable clinical conditions were studied. Clinical, echocardiographic parameters and circulating biomarkers were measured at baseline, after 30 and 60 days of S/V treatment. Both systolic blood pressure (SBP) and diastolic blood pressure (DBP) decreased, from 126 ± 15 to 113 ± 4 mmHg (p < 0.001) and from 77 ± 11 to 72 ± 9 mmHg (p = 0.005), respectively, at the end of study. Concomitantly, left ventricular ejection fraction (LVEF) increased by 22.8% from 29.5 ± 5% to 36.2 ± 5%, (p < 0.001) and indexed left ventricular end-systolic volume (LVESVi) decreased by 12% from 38.6 ± 8.7 ml/m2 to 34.0 ± 10.0 ml/m2. (p = 0.007). Circulating levels of PICP, YKL-40, PRA and Aldo decreased by - 42.2%, - 46.8%, - 79.1% and - 76.7%, respectively (p < 0.001 for all), the decrements being already maximal within 30 days of S/V treatment. No significant changes of plasma electrolytes and creatinine were observed during the study (all p > 0.05). CONCLUSIONS: A decrease of circulating markers of inflammation and fibrosis during chronic treatment with S/V is associated with an improvement of hemodynamic and echographic parameters in patients with HRrEF. These data are compatible with an anti-fibrotic and anti-inflammatory effect of S/V, that may contribute to the beneficial outcomes of the drug in this clinical setting.

Lipoprotein(a) and aortic valve stenosis: A casual or causal association?

AIMS: This review aims to provide an update of available methods for imaging calcification activity and potential therapeutic options. DATA SYNTHESIS: Aortic valve calcification represents the most common heart valve condition requiring treatment among adults in Western societies. No medical therapies are proven to be effective in treating symptoms or reducing disease progression. Therefore, surgical or transcatheter aortic valve replacement remains the only available treatment option. Elevated circulating concentrations of lipoprotein(a) is strongly associated with degenerative aortic stenosis. This relationship was first observed in prospective observational studies, and the causal relationship was confirmed in genetic studies. CONCLUSIONS: New therapeutic targets have been identified and new imaging techniques could be used to test the effectiveness of new agents and further clarify the pathophysiology of AVS. No therapy that specifically lowers Lp (a) levels has been approved for clinical use.

Prevalence of left atrial thrombus by real time three-dimensional echocardiography in patients undergoing electrical cardioversion of atrial fibrillation: A contemporary cohort study.

BACKGROUND: The prevalence of left atrial thrombi in patients scheduled for electrical cardioversion (ECV) of atrial fibrillation (AF) remains unknown in contemporary real-life practice. METHODS AND RESULTS: Patients scheduled for ECV underwent transesophageal echocardiography (TEE) regardless of AF duration and type of anticoagulant. Of 277 consecutive patients (65% men, mean age 71 ± 10 years, CHA2 DS2 -VASc 3.1 ± 1.4), 92 were on direct oral anticoagulants (DOACs) and 99 on antivitamin K (AVK) oral agents for at least 3 weeks before and 4 after ECV. Eighty-five patients with paroxysmal AF on low-molecular-weight heparin were also considered. Real time three-dimensional TEE detected left atrial appendage (LAA) thrombus in 7% of patients, without significant difference among three groups (P = .334). Anticoagulation was ineffective in eight patients on AVK oral agents, two of them had thrombus. Eight patients assumed incorrectly DOACs, four of them had thrombus. Among the 175 patients on effective anticoagulation, five showed thrombus, three on AVK oral agents, and two on DOACs (P = .716). Effective anticoagulation was associated with reduced risk of thrombosis (OR: 0.16, 95%CI: 0.06-0.45, P = .001). In patients with correct anticoagulation, predictors of thrombus were CHA2 DS2 VASc (for each point of increment OR: 1.97, 95%CI: 1.08-3.61, P = .029), low left ventricular ejection fraction (OR: 0.92, 95%CI: 0.86-0.99, P = .026), and degree of spontaneous echo-contrast (for each point increase OR: 10, 95%CI: 2-39, P < .0001). CONCLUSION: Patients with AF, on effective anticoagulation, had a prevalence of thrombus not negligible regardless of type of anticoagulant. TEE is prudent before ECV and mandatory if unsuccessful anticoagulation is proved or suspected.

Prognostic utility of quantitative offline 2D-echocardiography in hospitalized patients with COVID-19 disease.

PURPOSE: To assess the prognostic utility of quantitative 2D-echocardiography, including strain, in patients with COVID-19 disease. METHODS: COVID-19-infected patients admitted to the San Paolo University Hospital of Milan that underwent a clinically indicated echocardiographic examination were included in the study. To limit contamination, all measurements were performed offline. Quantitative measurements were obtained by an operator blinded to the clinical data. RESULTS: Among the 49 patients, nonsurvivors (33%) had worse respiratory parameters, index of multiorgan failure, and worse markers of lung involvement. Right ventricular (RV) dysfunction (as assessed by conventional and 2-dimensional speckle tracking) was a common finding and a powerful independent predictor of mortality. At the ROC curve analyses, RV free wall longitudinal strain (LS) showed an AUC 0.77 ± 0.08 in predicting death, P = .008, and global RV LS (RV-GLS) showed an AUC 0.79 ± 0.04, P = .004. This association remained significant after correction for age (OR = 1.16, 95%CI 1.01-1.34, P = .029 for RV free wall LS and OR = 1.20, 95%CI 1.01-1.42, P = .033 for RV-GLS), for oxygen partial pressure at arterial gas analysis/fraction of inspired oxygen (OR = 1.28, 95%CI 1.04-1.57, P = .021 for RV free wall-LS and OR = 1.30, 95%CI 1.04-1.62, P = .020 for RV-GLS) and for the severity of pulmonary involvement measured by a computed tomography lung score (OR = 1.27, 95%CI 1.02-1.19, P = .034 for RV free wall LS and OR = 1.30, 95%CI 1.04-1.63, P = .022 for RV-GLS). CONCLUSIONS: In patients hospitalized with COVID-19, offline quantitative 2D-echocardiographic assessment of cardiac function is feasible. Parameters of RV function are frequently abnormal and have an independent prognostic value over markers of lung involvement.

Unraveling the Enigma of Moderate Aortic Stenosis: Challenges and Future Prospects.

According to current guidelines, only clinical surveillance is recommended for patients with moderate aortic valve stenosis (AS), while aortic valve replacement may be considered in patients undergoing surgery for other indications. Recent studies have shown that moderate AS is associated with a high risk of adverse cardiovascular events, including death, especially in patients with left ventricular dysfunction. In this context, multimodality imaging can help to improve the accuracy of moderate AS diagnosis and to assess left ventricular remodeling response. This review discusses the natural history of this valve disease and the role of multimodality imaging in the diagnostic process, summarizes current evidence on the medical and non-medical management, and highlights ongoing trials on valve replacement.

Extensive myocardial calcifications: a systematic literature review of a rare pathological phenomenon.

Introduction: Myocardial calcifications (MC) represent a relatively rare pathological process, which may accompany different cardiovascular conditions and can be broadly categorized as dystrophic or metastatic. Myocardial infarction (MI) has been traditionally regarded as the main cause of MC overall; however, no updated comprehensive data on the relative incidence of different forms of MC is available. The purpose of this systematic review of the literature is to analyze the currently available evidence on MC in terms of pathophysiology, diagnosis, and clinical presentation. Methods and results: A total of 241 studies including a total of 368 patients affected by extensive MC were included in the final review. The majority of patients (69.8%) presented with dystrophic MC. Endomyocardial fibrosis (EMF) represents the single most common etiology of MC (24.2%), while sepsis/acute systemic inflammatory syndrome (SIRS) and chronic kidney disease were identified as the second and third most common causes respectively. The relative incidence of etiologies also varies across the years, with MI being more represented before 1990, and sepsis/SIRS becoming the single most common cause of MC after 1990. Multimodality imaging was used in the work-up of MC in 42.7% of cases. The most commonly employed imaging modality overall was echocardiography (51.9%), while after 1990 computed tomography scan became the most widely used tool (70.1%). Conclusion: The present systematic review provides new insights into the pathophysiology of MC. Previously thought to be mainly a consequence of ischemic heart disease, our data indicate that other diseases, namely EMF and sepsis/SIRS, are indeed the main conditions associated with MC. The importance of multimodality imaging in the work-up of MC is also highlighted.

Arrhythmogenic Mitral Valve Prolapse and Sudden Cardiac Death: An Update and Current Perspectives.

Mitral valve prolapse (MVP) affects about 2% to 3% of the general population, mostly women, and is the most common cause of primary chronic mitral regurgitation (MR) in western countries. The natural history is heterogeneous and widely determined by the severity of MR. Although most patients remain asymptomatic with a near-normal life expectancy, approximately 5% to 10 % progress to severe MR. As largely recognized, left ventricular (LV) dysfunction due to chronic volume overload per se identifies a subgroup at risk of cardiac death. However, there is rising evidence of a link between MVP and life threating ventricular arrhythmias (VAs)/sudden cardiac death (SCD) in a small subset of middle-aged patients without significant MR, heart failure and remodeled hearts. The present review focuses on the underlying mechanism of electric instability and unexpected cardiac death in this subset of young patients, from the myocardial scarring of the LV infero-lateral wall due to mechanical stretch exerted by the prolapsing leaflets and mitral annular disjunction, to the inflammation's impact on fibrosis pathways along with a constitutional hyperadrenergic state. The heterogeneity of clinical course reveals a necessity of risk stratification, preferably through noninvasive multimodality imaging, that will help to identify and prevent adverse scenarios in young MVP patients.

Aortic Valve Stenosis and Cancer: Problems of Management.

Aortic valve stenosis and malignancy frequently coexist and share the same risk factors as atherosclerotic disease. Data reporting the prognosis of patients with severe aortic stenosis and cancer are limited. Tailoring the correct and optimal care for cancer patients with severe aortic stenosis is complex. Cancer patients may be further disadvantaged by aortic stenosis if it interferes with their treatment by increasing the risk associated with oncologic surgery and compounding the risks associated with cardiotoxicity and heart failure (HF). Surgical valve replacement, transcatheter valve implantation, balloon valvuloplasty, and medical therapy are possible treatments for aortic valve stenosis, but when malignancy is present, the choice between these options must take into account the stage of cancer and associated treatment, expected outcome, and comorbidities. Physical examination and Doppler echocardiography are critical in the diagnosis and evaluation of aortic stenosis. The current review considers the available data on the association between aortic stenosis and cancer and the therapeutic options.

Role of cardiac and lung ultrasound in the COVID-19 era.

INTRODUCTION: The primary diagnostic method of Coronavirus disease 2019 is reverse transcription polymerase chain reaction of the nucleic acid of severe acute respiratory syndrome coronavirus 2 in nasopharyngeal swabs. There is growing evidence regarding the 2019 coronavirus disease imaging results on chest X-rays and computed tomography but the accessibility to standard diagnostic methods may be limited during the pandemic. EVIDENCE ACQUISITION: Databases used for the search were MEDLINE (PubMed), Scopus Search, and Cochrane Library. The research took into consideration studies published in English until March 2022 and was conducted using the following research query: ((((sars cov [MeSH Terms])) OR (COVID-19)) OR (Sars-Cov2)) OR (Coronavirus)) AND (((((2d echocardiography [MeSH Terms]) OR (doppler ultrasound imaging [MeSH Terms]))) OR (echography [MeSH Terms])) OR (LUS)) OR ("LUNG ULTRASOUND")). EVIDENCE SYNTHESIS: Pulmonary and cardiac ultrasound are cost-effective, widely available, and provide information that can influence management. CONCLUSIONS: Point-of-care ultrasonography is a method that can provide relevant clinical and therapeutic information in patients with COVID-19 where other diagnostic methods may not be easily accessible.

Long-Term Effects of Sacubitril-Valsartan on Cardiac Remodeling: A Parallel Echocardiographic Study of Left and Right Heart Adaptive Response.

Sacubitril/Valsartan (S/V) carries potential anti-remodeling properties, however long-term effects and biventricular adaptive response are poorly described. 76 HFrEF patients who underwent progressive uptitration of S/V, completed the annual scheduled follow-up. After a median follow-up of 11 (8-13) months, left ventricular (LV) reverse remodeling (RR) is defined as (1) absolute increase in LV ejection fraction (EF) ≥ 10% or LVEF ≥ 50% at follow-up and (2) decrease in indexed LV end-diastolic diameter (LVEDDi) of at least 10% or indexed LVEDDi ≤ 33 mm/m2, occurred in 27.6%. Non-ischemic etiology, shorter duration of HF, and absence of a history of AF were independently associated with LVRR (p < 0.05). TAPSE and TAPSE/PASP, a non-invasive index of right ventricular (RV) coupling to the pulmonary circulation, significantly improved at follow-up (0.45 vs. 0.56, p = 0.02). 41% of patients with baseline RV dysfunction obtained favorable RV remodeling despite only a moderate correlation between RV and LV function was observed (r = 0.478, p = 0.002). Our data point to a potential long-term reverse global remodeling effect by S/V, especially in patients who start S/V at an early stage of the disease, and focus our attention on a possible direct effect of the drug in synergistic hemodynamics between RV and pulmonary circulation.

Case Report: A rare homozygous patient affected by TTR systemic amyloidosis with a prominent heart involvement.

Hereditary transthyretin amyloidosis is a severe, adult-onset autosomal dominant inherited systemic disease predominantly affecting the peripheral and autonomic nervous system, heart, kidney, and the eyes. We present a case of a Caucasian 65-year-old man with cardiac amyloidosis and the homozygous mutation Val142Ile (classically, Val122Ile) in the transthyretin gene. We provide a genotype-phenotype correlation regarding the genetic status of both heterozygous and homozygous individuals and their clinical conditions at the time of genetic testing.

Use and Implications of Echocardiography in the Hemodynamic Assessment of Cardiogenic Shock.

Cardiogenic shock (CS) is a complex multisystem syndrome due to pump failure, associated with high mortality and morbidity. Its hemodynamic characterization is key to the diagnostic algorithm and management. Pulmonary artery catheterization is the gold standard for the left and right hemodynamic evaluation, but some concerns exist for invasivity and untoward mechanical and infective complications. Transthoracic echocardiography is a robust noninvasive diagnostic tool for hemodynamic multiparametric assessment that well applies to the management of CS. Its applications expand from etiology definition to the choice of therapeutic intervention and their monitoring. The present review aims at detailing the role of ultrasounds in CS emphasizing the clinical implications of combining cardiac and non-cardiac ultrasounds examinations that may correlate with prognosis.

The Global Burden of Valvular Heart Disease: From Clinical Epidemiology to Management.

Valvular heart disease is a leading cause of cardiovascular morbidity and mortality and a major contributor of symptoms and functional disability. Knowledge of valvular heart disease epidemiology and a deep comprehension of the geographical and temporal trends are crucial for clinical advances and the formulation of effective health policy for primary and secondary prevention. This review mainly focuses on the epidemiology of primary (organic, related to the valve itself) valvular disease and its management, especially emphasizing the importance of heart valve centers in ensuring the best care of patients through a multidisciplinary team.

Selection of patient for cardiac resynchronization therapy: role of QT corrected dispersion.

AIMS: About 30 to 50% of patients undergoing cardiac resynchronization therapy (CRT) may not show clinical or echocardiographic improvement, despite fulfilling guidelines recommendations for CRT. For this reason, we need a more accurate method to assess CRT eligibility. The aims of this study were to verify, on a 12-month follow-up, the usefulness of QT corrected dispersion (QTcD) in a patient's selection for CRT. METHODS: We stratified 53 patients who underwent CRT, into two groups based on the estimation of QTcD, that is, QTcD > 60 ms and QTcD ≤ 60 ms. In all patients were performed New York Heart Association (NYHA) class determination, six-minute walking test, QtcD, and QRS measurements, and complete echocardiographic assessment at 1, 3, 6, and 12 months after implantation. RESULTS: At baseline, there were no significant differences in clinical, echocardiographic, and electrocardiographic parameters duration between two groups. At 12-month follow-up between the two groups, there were significant differences in NYHA (1.2 ± 0.4 vs 2 ± 0.6; P < 0.01), six-minute walking distance (422 ± 68 vs 364 ± 68; P < 0.01), left ventricular (LV) ejection fraction (34 ± 7% vs 28 ± 6%; P < 0.01), LV end-diastolic diameter (57 ± 7 vs 63 ± 8; P < 0.01), and LV intraventricular dyssynchrony (24 ± 14 vs 39 ± 23; P < 0.01). CONCLUSION: This study suggests that QTc dispersion in addition to QRS duration could improve the sensitivity of electrocardiogram in a patient's selection for CRT.

Management of Dyslipidemia in Secondary Prevention of Cardiovascular Disease: The Gap between Theory and Practice.

Hypercholesterolemia is one of the most important modifiable risk factors for cardiovascular events (CV) representing the principal driving force in the development of atherosclerotic cardiovascular diseases (ASCVD) [...].

An Update on New Generation Transcatheter Aortic Valves and Delivery Systems.

Over the last 15 years, the management of aortic valve disease has been changed by transcatheter aortic valve replacement, which has become the standard of care across the entire spectrum of surgical risk. As a result of continuous evolution of this technique, several next-generation transcatheter heart valves (THVs) have been developed to minimize procedural complications and improve patient outcomes. This review aims to provide an update on the new generation THVs and delivery systems.

Risk of cardiovascular complications during non-cardiac surgery and preoperative cardiac evaluation.

The preoperative evaluation of candidates to non-cardiac surgery requires a knowledge of factors related both to the type of surgery and to the risk of each patient, in order to predict the potential cardiovascular complications. Over the past several decades, the field of preoperative cardiac evaluation before non-cardiac surgery has evolved substantially on the basis of the current guidelines of international medical societies. The aim of this paper is to summarize available evidence on the risk of non-cardiac surgery, focusing on appropriate cardiovascular assessment prior to surgery.

Impact of Right Ventricular-Pulmonary Circulation Coupling on Mortality in SARS-CoV-2 Infection.

Background The COVID-19-related pulmonary effects may negatively impact pulmonary hemodynamics and right ventricular function. We examined the prognostic relevance of right ventricular function and right ventricular-to-pulmonary circulation coupling assessed by bedside echocardiography in patients hospitalized with COVID-19 pneumonia and a large spectrum of disease independently of indices of pneumonia severity and left ventricular function. Methods and Results Consecutive COVID-19 subjects who underwent full cardiac echocardiographic evaluation along with gas analyses and computed tomography scans were included in the study. Measurements were performed offline, and quantitative analyses were obtained by an operator blinded to the clinical data. We analyzed 133 patients (mean age 69±12 years, 57% men). During a mean hospital stay of 26±16 days, 35 patients (26%) died. The mean tricuspid annular plane systolic excursion/pulmonary artery systolic pressure (TAPSE/PASP) ratio was 0.48±0.18 mm/Hg in nonsurvivors and 0.72±0.32 mm/Hg in survivors (P=0.002). For each 0.1 mm/mm Hg increase in TAPSE/PASP, there was a 27% lower risk of in-hospital death (hazard ratio [HR], 0.73 [95% CI, 0.59-0.89]; P=0.003). At multivariable analysis, TAPSE/PASP ratio remained a predictor of in-hospital death after adjustments for age, oxygen partial pressure at arterial gas analysis/fraction of inspired oxygen, left ventricular ejection fraction, and computed tomography lung score. Receiver operating characteristic analysis was used to identify the cutoff value of the TAPSE/PASP ratio, which best specified high-risk from lower-risk patients. The best cutoff for predicting in-hospital mortality was TAPSE/PASP <0.57 mm/mm Hg (75% sensitivity and 70% specificity) and was associated with a >4-fold increased risk of in-hospital death (HR, 4.8 [95% CI, 1.7-13.1]; P=0.007). Conclusions In patients hospitalized with COVID-19 pneumonia, the assessment of right ventricular to pulmonary circulation coupling appears central to disease evolution and prediction of events. TAPSE/PASP ratio plays a mainstay role as prognostic determinant beyond markers of lung injury.

Prevalence and Rate of Resolution of Left Atrial Thrombus in Patients with Non-Valvular Atrial Fibrillation: A Two-Center Retrospective Real-World Study.

BACKGROUND AND AIM: Thromboembolic events due to left atrial appendage (LAA) thrombosis are the main complication of non-valvular atrial fibrillation (NVAF). Although anticoagulants are effective in patients with NVAF, a minimal residual thromboembolic risk persists. Little is known about the prevalence of LAA thrombus and the rate of resolution after the recommended period of anticoagulation therapy, including vitamin K antagonists (VKA), heparin, and non-vitamin K antagonist oral anticoagulants (NOACs). METHODS AND RESULTS: We aimed to study the prevalence of LAA thrombus in an unselected cohort of patients undergoing transesophageal echocardiogram (TEE), and the determinants of LAA thrombus resolution. We retrospectively analyzed 8888 consecutive TEEs performed over five years in two high-volume centers and included all patients with LAA thrombus. A total of 265 patients (3%) had an LAA thrombus. Among these, 97% presented with AF. Fifty-eight percent of patients were on anticoagulants at least three weeks before the diagnosis. After the LAA thrombus diagnosis, VKAs were prescribed in 52%, heparin in 18.5%, and NOAC in 27% of patients. Among the 183 patients with repeat TEE, performed at (25-75th) 39 days (21-84), 67% showed resolution of the LAA thrombus. Although the rate of thrombus resolution was higher in patients treated with NOACs (NOACs 71%, VKA 66%, Heparin 60%) the difference between anticoagulants was statistically non-significant (VKA, OR 0.9, p = 0.83; NOAC, OR 1.23, p = 0.42; heparin, OR 0.69, p = 0.35). Thus, NOACs were demonstrated to be at least as effective as other anticoagulants in the rate of LAA thrombus resolution. Upon multivariate-adjusted analysis, higher LAA emptying velocities were the only predictor of thrombus resolution. In conclusion, the majority of patients were already on anticoagulants. NOACs could be at least as effective as other anticoagulants, yielding an LAA thrombus resolution in two-thirds of patients. This may have clinical relevance, especially in patients undergoing cardioversion or catheter ablation.