Exercise Stress Echocardiography of the Right Ventricle and Pulmonary Circulation.

BACKGROUND: Exercise echocardiography is used for assessment of pulmonary circulation and right ventricular function, but limits of normal and disease-specific changes remain insufficiently established. OBJECTIVES: The objective of this study was to explore the physiological vs pathologic response of the right ventricle and pulmonary circulation to exercise. METHODS: A total of 2,228 subjects were enrolled: 375 healthy controls, 40 athletes, 516 patients with cardiovascular risk factors, 17 with pulmonary arterial hypertension, 872 with connective tissue diseases without overt pulmonary hypertension, 113 with left-sided heart disease, 30 with lung disease, and 265 with chronic exposure to high altitude. All subjects underwent resting and exercise echocardiography on a semirecumbent cycle ergometer. All-cause mortality was recorded at follow-up. RESULTS: The 5th and 95th percentile of the mean pulmonary artery pressure-cardiac output relationships were 0.2 to 3.5 mm Hg.min/L in healthy subjects without cardiovascular risk factors, and were increased in all patient categories and in high altitude residents. The 5th and 95th percentile of the tricuspid annular plane systolic excursion to systolic pulmonary artery pressure ratio at rest were 0.7 to 2.0 mm/mm Hg at rest and 0.5 to 1.5 mm/mm Hg at peak exercise, and were decreased at rest and exercise in all disease categories and in high-altitude residents. An increased all-cause mortality was predicted by a resting tricuspid annular plane systolic excursion to systolic pulmonary artery pressure <0.7 mm/mm Hg and mean pulmonary artery pressure-cardiac output >5 mm Hg.min/L. CONCLUSIONS: Exercise echocardiography of the pulmonary circulation and the right ventricle discloses prognostically relevant differences between healthy subjects, athletes, high-altitude residents, and patients with various cardio-respiratory conditions. (Right Heart International NETwork During Exercise in Different Clinical Conditions; NCT03041337).

Cardiovascular Side Effects of Anthracyclines and HER2 Inhibitors among Patients with Breast Cancer: A Multidisciplinary Stepwise Approach for Prevention, Early Detection, and Treatment.

Cardiovascular (CV) diseases (CVD) are a major cause of long-term morbidity and mortality affecting life expectancy amongst cancer survivors. In recent years, because of the possibility of early diagnosis and the increased efficacy of neo-adjuvant and adjuvant systemic treatments (targeting specific molecular pathways), the high percentage of survival from breast cancer led CVD to become the first cause of death among survivors. Therefore, it is mandatory to adopt cardioprotective strategies to minimize CV side effects and CVD in general in breast cancer patients. Cancer therapeutics-related cardiac dysfunction (CTRCD) is a common group of side effects of chemotherapeutics widely employed in breast cancer (e.g., anthracycline and human epidermal growth factor receptor 2 inhibitors). The aim of the present manuscript is to propose a pragmatic multidisciplinary stepwise approach for prevention, early detection, and treatment of cardiotoxicity in patients with breast cancer.

Acute Heart Failure: Diagnostic-Therapeutic Pathways and Preventive Strategies-A Real-World Clinician's Guide.

Acute heart failure (AHF) is the most frequent cause of unplanned hospital admission in patients of >65 years of age and it is associated with significantly increased morbidity, mortality, and healthcare costs. Different AHF classification criteria have been proposed, mainly reflecting the clinical heterogeneity of the syndrome. Regardless of the underlying mechanism, peripheral and/or pulmonary congestion is present in the vast majority of cases. Furthermore, a marked reduction in cardiac output with peripheral hypoperfusion may occur in most severe cases. Diagnosis is made on the basis of signs and symptoms, laboratory, and non-invasive tests. After exclusion of reversible causes, AHF therapeutic interventions mainly consist of intravenous (IV) diuretics and/or vasodilators, tailored according to the initial hemodynamic status with the addition of inotropes/vasopressors and mechanical circulatory support if needed. The aim of this review is to discuss current concepts on the diagnosis and management of AHF in order to guide daily clinical practice and to underline the unmet needs. Preventive strategies are also discussed.

Exploring the Cardiotoxicity Spectrum of Anti-Cancer Treatments: Definition, Classification, and Diagnostic Pathways.

Early detection and treatment of cancer have led to a noticeable reduction in both mortality and morbidity. However, chemotherapy and radiotherapy could exert cardiovascular (CV) side effects, impacting survival and quality of life, independent of the oncologic prognosis. In this regard, a high clinical index of suspicion is required by the multidisciplinary care team in order to trigger specific laboratory tests (namely natriuretic peptides and high-sensitivity cardiac troponin) and appropriate imaging techniques (transthoracic echocardiography along with cardiac magnetic resonance, cardiac computed tomography, and nuclear testing (if clinically indicated)), leading to timely diagnosis. In the near future, we do expect a more tailored approach to patient care within the respective community along with the widespread implementation of digital health tools.

Severe Stenosis of Mitral Bioprosthetic Valve Thrombosis in a Patient with HCV-Related Cirrhosis and Duodenal Variceal Bleeding: The Deadly Triad.

Bioprosthetic valve thrombosis (BPVT) is considered a relatively rare but life-threatening clinical entity. Thus, there is the need of high clinical suspicion in order to make a timely diagnosis and related appropriate therapeutic interventions. In this regard, the management of BPVT is high risk, whatever the option taken (surgery and/or systemic fibrinolysis). The presence of severe comorbidities-as decompensated cirrhosis-further complicates the clinical decision-making process, calling for a patient-tailored integrated multidisciplinary approach. We report a challenging case of a 45-year-old patient with mitral bioprosthetic valve thrombosis and hepatitis C virus (HCV)-related cirrhosis complicated by active duodenal variceal bleeding.

Effects of Exercise on Heart Failure with Preserved Ejection Fraction: An Updated Review of Literature.

Heart failure with preserved ejection fraction (HFpEF) represents the most common HF phenotype of patients aged > 65 years, with an incidence and a prevalence that are constantly growing. The HFpEF cardinal symptom is exercise intolerance (EI), defined as the impaired ability to perform physical activity and to reach the predicted age-related level of exercise duration in the absence of symptoms­such as fatigue or dyspnea­and is associated with a poor quality of life, a higher number of hospitalizations, and poor outcomes. The evidence of the protective effect between exercise and adverse cardiovascular outcomes is numerous and long-established. Regular exercise is known to reduce cardiovascular events and overall mortality both in apparently healthy individuals and in patients with established cardiovascular disease, representing a cornerstone in the prevention and treatment of many cardio-metabolic conditions. Several studies have investigated the role of exercise in HFpEF patients. The present review aims to dwell upon the effects of exercise on HFpEF. For this purpose, the relevant data from a literature search (PubMed, EMBASE, and Medline) were reviewed. The analysis of these studies underlines the fact that exercise training programs improve the cardiorespiratory performance of HFpEF patients in terms of the increase in peak oxygen uptake, the 6 min walk test distance, and the ventilatory threshold; on the other hand, diastolic or systolic functions are generally unchanged or only partially modified by exercise, suggesting that multiple mechanisms contribute to the improvement of exercise tolerance in HFpEF patients. In conclusion, considering that exercise training programs are able to improve the cardiorespiratory performance of HFpEF patients, the prescription of exercise training programs should be encouraged in stable HFpEF patients, and further research is needed to better elucidate the pathophysiological mechanisms underpinning the beneficial effects described.

Physiologic Range of Myocardial Mechano-Energetic Efficiency among Healthy Subjects: Impact of Gender and Age.

BACKGROUND: Myocardial mechano-energetic efficiency (MEE) is the capability of the left ventricle (LV) to convert the chemical energy obtained from the cardiac oxidative metabolism into mechanical work. The aim of present study was to establish normal non-invasive MEE and MEEi reference values. METHODS: In total, 1168 healthy subjects underwent physical examinations, clinical assessment, and standardized transthoracic echocardiographic (TTE) examination. MEE was obtained by TTE as the ratio between stroke volume (SV) and heart rate (HR): MEE = SV/HR [HR expressed in seconds (HR/60)]. Because MEE is highly related to left ventricular mass (LVM), MEE was then divided by LVM with the purpose of obtaining an estimate of energetic expenditure per unit of myocardial mass (i.e., indexed MEE, MEEi, mL/s/g). RESULTS: The mean values of MEE and MEEi in the overall population were 61.09 ± 18.19 mL/s; 0.45 ± 0.14, respectively. In a multivariable analysis, gender, body surface area (BSA), diastolic blood pressure, left atrial volume indexed to BSA, E/e' and tricuspid annular plane systolic excursion (TAPSE) were the independent variables associated with MEE, while age, gender, BSA and TAPSE were the independent variables associated with MEEi. CONCLUSIONS: The knowledge of age- and gender-based MEE and MEEi normal values may improve the global assessment of LV cardiac mechanics and serve as a reference to identify phenotypes at high risk of cardiovascular events.

Right Heart Pulmonary Circulation Unit Response to Exercise in Patients with Controlled Systemic Arterial Hypertension: Insights from the RIGHT Heart International NETwork (RIGHT-NET).

BACKGROUND: Systemic arterial hypertension (HTN) is the main risk factor for the development of heart failure with preserved ejection fraction (HFpEF). The aim of the study was was to assess the trends in PASP, E/E' and TAPSE during exercise Doppler echocardiography (EDE) in hypertensive (HTN) patients vs. healthy subjects stratified by age. METHODS: EDE was performed in 155 hypertensive patients and in 145 healthy subjects (mean age 62 ± 12.0 vs. 54 ± 14.9 years respectively, p < 0.0001). EDE was undertaken on a semi-recumbent cycle ergometer with load increasing by 25 watts every 2 min. Left ventricular (LV) and right ventricular (RV) dimensions, function and hemodynamics were evaluated. RESULTS: Echo-Doppler parameters of LV and RV function were lower, both at rest and at peak exercise in hypertensives, while pulmonary hemodynamics were higher as compared to healthy subjects. The entire cohort was then divided into tertiles of age: at rest, no significant differences were recorded for each age group between hypertensives and normotensives except for E/E' that was higher in hypertensives. At peak exercise, hypertensives had higher pulmonary artery systolic pressure (PASP) and E/E' but lower tricuspid annular plane systolic excursion (TAPSE) as age increased, compared to normotensives. Differences in E/E' and TAPSE between the 2 groups at peak exercise were explained by the interaction between HTN and age even after adjustment for baseline values (p < 0.001 for E/E', p = 0.011 for TAPSE). At peak exercise, the oldest group of hypertensive patients had a mean E/E' of 13.0, suggesting a significant increase in LV diastolic pressure combined with increased PASP. CONCLUSION: Age and HTN have a synergic negative effect on E/E' and TAPSE at peak exercise in hypertensive subjects.

Reference Ranges of Left Ventricular Hemodynamic Forces in Healthy Adults: A Speckle-Tracking Echocardiographic Study.

BACKGROUND: The normal limits of left ventricular (LV) hemodynamic forces (HDFs) are not exactly known. The aim of this study was to explore the full spectrum of HDF parameters in healthy subjects and determine their physiologic correlates. METHODS: 269 healthy subjects were enrolled (mean age: 43 ± 14 years; 123 (45.7%) men). All participants underwent an echo-Doppler examination. Tri-plane tissue tracking from apical views was used to measure 2D global endocardial longitudinal strain (GLS), circumferential strain (GCS), and LV HDFs. HDFs were normalized with LV volume and divided by specific weight. RESULTS: LV systolic longitudinal HDFs (%) were higher in men (20.8 ± 6.5 vs. 18.9 ± 5.6, p = 0.009; 22.0 ± 6.7 vs. 19.8 ± 5.6, p = 0.004, respectively). There was a significant correlation between GCS (increased) (r = -0.240, p < 0.001) and LV longitudinal HDFs (reduced) (r = -0.155, p = 0.01) with age. In a multivariable analysis age, BSA, pulse pressure, heart rate and GCS were the only independent variables associated with LV HDFs (ß coefficient = -0.232, p < 0.001; 0.149, p = 0.003; 0.186, p < 0.001; 0.396, p < 0.001; -0.328, p < 0.001; respectively). CONCLUSION: We report on the physiologic range of LV HDFs. Knowledge of reference values of HDFs may prompt their implementation into clinical routine and allow a more comprehensive assessment of the LV function.

Preoperative Assessment and Management of Cardiovascular Risk in Patients Undergoing Non-Cardiac Surgery: Implementing a Systematic Stepwise Approach during the COVID-19 Pandemic Era.

Major adverse cardiac events, defined as death or myocardial infarction, are common causes of perioperative mortality and major morbidity in patients undergoing non-cardiac surgery. Reduction of perioperative cardiovascular risk in relation to non-cardiac surgery requires a stepwise patient evaluation that integrates clinical risk factors, functional status and the estimated stress of the planned surgical procedure. Major guidelines on preoperative cardiovascular risk assessment recommend to establish, firstly, the risk of surgery per se (low, moderate, high) and the related timing (elective vs. urgent/emergent), evaluate the presence of unstable cardiac conditions or a recent coronary revascularization (percutaneous coronary intervention or coronary artery bypass grafting), assess the functional capacity of the patient (usually expressed in metabolic equivalents), determine the value of non-invasive and/or invasive cardiovascular testing and then combine these data in estimating perioperative risk for major cardiac adverse events using validated scores (Revised Cardiac Risk Index (RCRI) or National Surgical Quality Improvement Program (NSQIP)). This stepwise approach has the potential to guide clinicians in determining which patients could benefit from cardiovascular therapy and/or coronary artery revascularization before non-cardiac surgery towards decreasing the incidence of perioperative morbidity and mortality. Finally, it should be highlighted that there is a need to implement specific strategies in the 2019 Coronavirus disease (COVID-19) pandemic to minimize the risk of transmission of COVID-19 infection during the preoperative risk assessment process.

Successful surgical repair of left ventricular pseudoaneurysm in a patient with subacute ST-elevation myocardial infarction.

We report a successful surgical repair of left ventricular pseudoaneurysm in a patient with subacute ST-elevation myocardial infarction (STEMI). In the case of expansion of the infarct related ventricular wall, early (within 24 hours) or late (3-5 days after STEMI) cardiac rupture should be always borne in mind in order to proceed to life saving prompt surgical repair.

A giant mediastinal teratoma: From diagnosis to complete resection and restitutio ad integrum.

The current report highlights the integrated work-up of an unexpected giant mediastinal teratoma in 28 years old female. A comprehensive multi-modality imaging approach was implemented in order to define the diagnosis and tailor the most appropriate surgical intervention.

Reshaping of Italian Echocardiographic Laboratories Activities during the Second Wave of COVID-19 Pandemic and Expectations for the Post-Pandemic Era.

BACKGROUND: Cardiology divisions reshaped their activities during the coronavirus disease 2019 (COVID-19) pandemic. This study aimed to analyze the organization of echocardiographic laboratories and echocardiography practice during the second wave of the COVID-19 pandemic in Italy, and the expectations for the post-COVID era. METHODS: We analyzed two different time periods: the month of November during the second wave of the COVID-19 pandemic (2020) and the identical month during 2019 (November 2019). RESULTS: During the second wave of the COVID-19 pandemic, the hospital activity was partially reduced in 42 (60%) and wholly interrupted in 3 (4%) echocardiographic laboratories, whereas outpatient echocardiographic activity was partially reduced in 41 (59%) and completely interrupted in 7 (10%) laboratories. We observed an important change in the organization of activities in the echocardiography laboratory which reduced the operator-risk and improved self-protection of operators by using appropriate personal protection equipment. Operators wore FFP2 in 58 centers (83%) during trans-thoracic echocardiography (TTE), in 65 centers (93%) during transesophageal echocardiography (TEE) and 63 centers (90%) during stress echocardiography. The second wave caused a significant reduction in number of echocardiographic exams, compared to November 2019 (from 513 ± 539 to 341 ± 299 exams per center, -34%, p < 0.001). On average, there was a significant increase in the outpatient waiting list for elective echocardiographic exams (from 32.0 ± 28.1 to 45.5 ± 44.9 days, +41%, p < 0.001), with a reduction of in-hospital waiting list (2.9 ± 2.4 to 2.4 ± 2.0 days, -17%, p < 0.001). We observed a large diffusion of point-of-care cardiac ultrasound (88%), with a significant increase of lung ultrasound usage in 30 centers (43%) during 2019, extended to all centers in 2020. Carbon dioxide production by examination is an indicator of the environmental impact of technology (100-fold less with echocardiography compared to other cardiac imaging techniques). It was ignored in 2019 by 100% of centers, and currently it is considered potentially crucial for decision-making in cardiac imaging by 65 centers (93%). CONCLUSIONS: In one year, major changes occurred in echocardiography practice and culture. The examination structure changed with extensive usage of point-of-care cardiac ultrasound and with lung ultrasound embedded by default in the TTE examination, as well as the COVID-19 testing.

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.

Age-changes in right ventricular function-pulmonary circulation coupling: from pediatric to adult stage in 1899 healthy subjects. The RIGHT Heart International NETwork (RIGHT-NET).

The present study analyzes age-specific changes in RV function and RV-PA coupling in a large cohort of apparently healthy subjects with a wide age-range, to identify reference values and to study the influence of clinical and echocardiographic cofactors. 1899 Consecutive healthy subjects underwent a standardized transthoracic echocardiographic examination. Tricuspid annular plane systolic excursion (TAPSE) and systolic pulmonary artery pressure (SPAP) were measured. Ventriculo-arterial coupling was then inferred from the TAPSE/SPAP ratio. A quantile regression analysis was used to estimate quantiles 0.05, 0.10, 0.50 (median), 0.90, and 0.95 of TAPSE, SPAP and TAPSE/SPAP. The association between age and each of these values was determined. The mean age of the group was 45.2 ± 18.5 years (range 1 to 102 years), 971 were males. SPAP increased with age, whereas TAPSE and TAPSE/SPAP ratio decreased. Upon multivariate modeling, the most significant positive associations for TAPSE were body surface area (BSA) driven by the pediatric group, stroke volume (SV), E/A and negatively heart rate and E/e' ratio. SPAP was positively associated with increasing age, SV, E/A, E/e' and negatively with BSA. TAPSE/SPAP ratio was negatively associated with age, female sex, and E/e' and positively with BSA. A preserved relationship between TAPSE and SPAP was found across the different age groups. TAPSE, SPAP and TAPSE/SPAP demonstrate important trends and associations with advancing age, impaired diastolic function, affected by female sex and BSA However the relationship between TAPSE and SPAP is relatively well preserved across the age spectrum.

Feasibility of semi-recumbent bicycle exercise Doppler echocardiography for the evaluation of the right heart and pulmonary circulation unit in different clinical conditions: the RIGHT heart international NETwork (RIGHT-NET).

Exercise Doppler echocardiography (EDE) is a well-validated tool in ischemic and valvular heart diseases. However, its use in the assessment of the right heart and pulmonary circulation unit (RH-PCU) is limited. The aim of this study is to assess the semi-recumbent bicycle EDE feasibility for the evaluation of RH-PCU in a large multi-center population, from healthy individuals and elite athletes to patients with overt or at risk of developing pulmonary hypertension (PH). From January 2019 to July 2019, 954 subjects [mean age 54.2 ± 16.4 years, range 16-96, 430 women] underwent standardized semi-recumbent bicycle EDE with an incremental workload of 25 watts every 2 min, were prospectively enrolled among 7 centers participating to the RIGHT Heart International NETwork (RIGHT-NET). EDE parameters of right heart structure, function and pressures were obtained according to current recommendations. Right ventricular (RV) function at peak exercise was feasible in 903/940 (96%) by tricuspid annular plane systolic excursion (TAPSE), 667/751 (89%) by tissue Doppler-derived tricuspid lateral annular systolic velocity (S') and 445/672 (66.2%) by right ventricular fractional area change (RVFAC). RV-right atrial pressure gradient [RV-RA gradient = 4 × tricuspid regurgitation velocity2 (TRV)] was feasible in 894/954 patients (93.7%) at rest and in 816/954 (85.5%) at peak exercise. The feasibility rate in estimating pulmonary artery pressure improved to more than 95%, if both TRV and/or right ventricular outflow tract acceleration time (RVOT AcT) were considered. In high specialized echocardiography laboratories semi-recumbent bicycle EDE is a feasible tool for the assessment of the RH-PCU pressure and function.

Cardiac teleconsulting in the time of COVID-19 global pandemic: The "Antonio Cardarelli" Hospital project.

Dear Editor, Teleconsulting - defined as real-time consultation between doctors by exploiting video conferencing technology over the Internet network - is exponentially being implemented through the western world lastly triggered by COVID-19 pandemic...

A multicentric quality-control study of exercise Doppler echocardiography of the right heart and the pulmonary circulation. The RIGHT Heart International NETwork (RIGHT-NET).

PURPOSE: This study was a quality-control study of resting and exercise Doppler echocardiography (EDE) variables measured by 19 echocardiography laboratories with proven experience participating in the RIGHT Heart International NETwork. METHODS: All participating investigators reported the requested variables from ten randomly selected exercise stress tests. Intraclass correlation coefficients (ICC) were calculated to evaluate the inter-observer agreement with the core laboratory. Inter-observer variability of resting and peak exercise tricuspid regurgitation velocity (TRV), right ventricular outflow tract acceleration time (RVOT Act), tricuspid annular plane systolic excursion (TAPSE), tissue Doppler tricuspid lateral annular systolic velocity (S'), right ventricular fractional area change (RV FAC), left ventricular outflow tract velocity time integral (LVOT VTI), mitral inflow pulsed wave Doppler velocity (E), diastolic mitral annular velocity by TDI (e') and left ventricular ejection fraction (LVEF) were measured. RESULTS: The accuracy of 19 investigators for all variables ranged from 99.7 to 100%. ICC was > 0.90 for all observers. Inter-observer variability for resting and exercise variables was for TRV = 3.8 to 2.4%, E = 5.7 to 8.3%, e' = 6 to 6.5%, RVOT Act = 9.7 to 12, LVOT VTI = 7.4 to 9.6%, S' = 2.9 to 2.9% and TAPSE = 5.3 to 8%. Moderate inter-observer variability was found for resting and peak exercise RV FAC (15 to 16%). LVEF revealed lower resting and peak exercise variability of 7.6 and 9%. CONCLUSIONS: When performed in expert centers EDE is a reproducible tool for the assessment of the right heart and the pulmonary circulation.

Cardiovascular Magnetic Resonance in Right Heart and Pulmonary Circulation Disorders.

Right heart and pulmonary circulation disorders are generally caused by right ventricle (RV) pressure overload, volume overload, and cardiomyopathy, and they are associated with distinct clinical courses and therapeutic approaches, although they often may coexist. Cardiac magnetic resonance (CMR) provides a noninvasive accurate and reproducible multiplanar anatomic and functional assessment, tissue characterization, and blood flow evaluation of the right heart and pulmonary circulation. This article reviews the current status of the CMR, the most recent techniques, the new parameters and their clinical utility in diagnosis, prognosis, and therapeutic management in the right heart and pulmonary circulation disorders.