Role of speckle tracking echocardiography beyond current guidelines in cardiac resynchronization therapy.

Cardiac resynchronization therapy (CRT) is a device-based treatment applied to patients with a specific profile of heart failure. According to current guidelines, indication for CRT is given on the basis of QRS morphology and duration, and traditional transthoracic echocardiography is mainly used to estimate left ventricular (LV) ejection fraction. However, the identification of patients who may benefit from CRT remains challenging, since the application of the above-mentioned guidelines is still associated with a high rate of non-responders. The assessment of various aspects of LV mechanics (including contractile synchrony, coordination and propagation, and myocardial work) performed by conventional and novel ultrasound technologies, first of all speckle tracking echocardiography (STE), may provide additional, useful information for CRT patients' selection, in particular among non-LBBB patients, who generally respond less to CRT. A multiparametric approach, based on the combination of ECG criteria and echocardiographic indices of LV dyssynchrony/discoordination would be desirable to improve the prediction of CRT response.

Left atrial expansion index measured with cardiovascular magnetic resonance estimates pulmonary capillary wedge pressure in dilated cardiomyopathy.

BACKGROUND: Pulmonary capillary wedge pressure (PCWP) assessment is fundamental for managing dilated cardiomyopathy (DCM) patients. Although cardiovascular magnetic resonance (CMR) has become the gold-standard imaging technique for evaluating cardiac chamber volume and function, PCWP is not routinely assessed with CMR. Therefore, this study aimed to validate the left atrial expansion index (LAEI), a LA reservoir function parameter able to estimate filling pressure with echocardiography, as a novel CMR-measured parameter for non-invasive PCWP estimation in DCM patients. METHODS: We performed a retrospective, single-center, cross-sectional study. We included electively admitted DCM patients referred to our tertiary center for further diagnostic evaluation that underwent a clinically indicated right heart catheterization (RHC) and CMR within 24 h. PCWP invasively measured during RHC was used as the reference. LAEI was calculated from CMR-measured LA maximal and minimal volumes as LAEI = ( (LAVmax-LAVmin)/LAVmin) × 100. RESULTS: We enrolled 126 patients (47 ± 14 years; 68% male; PCWP = 17 ± 9.3 mmHg) randomly divided into derivation (n = 92) and validation (n = 34) cohorts with comparable characteristics. In the derivation cohort, the log-transformed (ln) LAEI showed a strong linear correlation with PCWP (r = 0.81, p < 0.001) and remained a strong independent PCWP determinant over clinical and conventional CMR parameters. Moreover, lnLAEI accurately identified PCWP ≥ 15 mmHg (AUC = 0.939, p < 0.001), and the optimal cut-off identified (lnLAEI ≤ 3.85) in the derivation cohort discriminated PCWP ≥ 15 mmHg with 82.4% sensitivity, 88.2% specificity, and 85.3% accuracy in the validation cohort. Finally, the equation PCWP = 52.33- (9.17xlnLAEI) obtained from the derivation cohort predicted PCWP (-0.1 ± 5.7 mmHg) in the validation cohort. CONCLUSIONS: In this cohort of DCM patients, CMR-measured LAEI resulted in a novel and useful parameter for non-invasive PCWP evaluation.

Dyspnea in Post-Acute COVID-19: A Multi-Parametric Cardiopulmonary Evaluation.

Post-acute COVID-19 is characterized by the persistence of dyspnea, but the pathophysiology is unclear. We evaluated the prevalence of dyspnea during follow-up and factors at admission and follow-up associated with dyspnea persistence. After five months from discharge, 225 consecutive patients hospitalized for moderate to severe COVID-19 pneumonia were assessed clinically and by laboratory tests, echocardiography, six-minute walking test (6MWT), and pulmonary function tests. Fifty-one patients reported persistent dyspnea. C-reactive protein (p = 0.025, OR 1.01 (95% CI 1.00-1.02)) at admission, longer duration of hospitalization (p = 0.005, OR 1.05 (95% CI 1.01-1.10)) and higher body mass index (p = 0.001, OR 1.15 (95% CI 1.06-1.28)) were independent predictors of dyspnea. Absolute drop in SpO2 at 6MWT (p = 0.001, OR 1.37 (95% CI 1.13-1.69)), right ventricular (RV) global longitudinal strain (p = 0.016, OR 1.12 (95% CI 1.02-1.25)) and RV global longitudinal strain/systolic pulmonary artery pressure ratio (p = 0.034, OR 0.14 (95% CI 0.02-0.86)) were independently associated with post-acute COVID-19 dyspnea. In conclusion, dyspnea is present in many patients during follow-up after hospitalization for COVID-19 pneumonia. While higher body mass index, C-reactive protein at admission, and duration of hospitalization are predictors of persistent dyspnea, desaturation at 6MWT, and echocardiographic RV dysfunction are associated with this symptom during the follow-up period.

Effect of Aging on Intraventricular Kinetic Energy and Energy Dissipation.

In recent years, analysis of kinetic energy (KE) and the rate of kinetic energy dissipation (KED) or energy loss (EL) within the cardiac chambers, obtained by cardiac imaging techniques, has gained increasing attention. Thus, there is a need to clarify the effect of physiological variables, specifically aging, on these energetic measures. To elucidate this aspect, we reviewed the literature on this topic. Overall, cardiac magnetic resonance and echocardiographic studies published so far indicate that aging affects the energetics of left and right intraventricular blood flow, although not all energy measures during the cardiac cycle seem to be affected by age in the same way. Current studies, however, have limitations. Additional large, multicenter investigations are needed to test the effect of physiological variables on intraventricular KE and KED/EL measures.

Relative apical sparing in cardiac amyloidosis is not always explained by an amyloid gradient.

AIMS: Myocardial longitudinal strain (LS) by two-dimensional (2D) speckle-tracking echocardiography has a diagnostic and prognostic role in cardiac amyloidosis (CA). Typically, the apical segments of the left ventricle (LV) are less affected by LS abnormalities, a finding called relative apical sparing (RELAPS). Whether a variable burden of CA might explain the RELAPS remains unknown.We aimed to evaluate the extent, distribution, and deposition pattern of amyloid in autopsy hearts of CA patients and to correlate the histopathology findings with 2D echocardiography. METHODS AND RESULTS: This is a retrospective study of whole heart specimens of CA patients who died and underwent autopsy and 2D echocardiography. Amyloid burden quantification was assessed by histomorphometry in each segment at different LV levels. The LS analysis results were compared with the amyloid burden and the base-to-apex distribution.Histopathology investigation of 27 hearts with CA [immunoglobulin light chains (AL) 17 cases and transthyretin (ATTR) 10 cases] demonstrated an amyloid base-to-apex gradient. In 11 CA patients with 2D echocardiography, analysis of LS and histological amyloid burden allowed to identify different patterns: RELAPS (8 cases, 73%), with (2) or without (6) amyloid gradient, normal or mildly reduced LS with diffuse low amyloid (2, 18%), and severely reduced LS with diffuse high amyloid (1, 9%). CONCLUSION: The typical RELAPS pattern at echocardiography is not always explained by a base-to-apex gradient of amyloid burden at histopathology, suggesting that RELAPS might be an epiphenomenon of complex interactions among amyloid infiltration, myocardial structure, and adaptation.

Subclinical Myocardial Injury in Patients Recovered from COVID-19 Pneumonia: Predictors and Longitudinal Assessment.

(1) Background: Emerging data regarding patients recovered from COVID-19 are reported in the literature, but cardiac sequelae have not yet been clarified. To quickly detect any cardiac involvement at follow-up, the aims of the research were to identify: elements at admission predisposing subclinical myocardial injury at follow up; the relationship between subclinical myocardial injury and multiparametric evaluation at follow-up; and subclinical myocardial injury longitudinal evolution. (2) Methods and Results: A total of 229 consecutive patients hospitalised for moderate to severe COVID-19 pneumonia were initially enrolled, of which 225 were available for follow-up. All patients underwent a first follow-up visit, which included a clinical evaluation, a laboratory test, echocardiography, a six-minute walking test (6MWT), and a pulmonary functional test. Of the 225 patients, 43 (19%) underwent a second follow-up visit. The median time to the first follow-up after discharge was 5 months, and the median time to the second follow-up after discharge was 12 months. Left ventricular global longitudinal strain (LVGLS) and right ventricular free wall strain (RVFWS) were reduced in 36% (n = 81) and 7.2% (n = 16) of the patients, respectively, at first the follow-up visit. LVGLS impairment showed correlations with patients of male gender (p 0.008, OR 2.32 (95% CI 1.24-4.42)), the presence of at least one cardiovascular risk factor (p < 0.001, OR 6.44 (95% CI 3.07-14.9)), and final oxygen saturation (p 0.002, OR 0.99 (95% CI 0.98-1)) for the 6MWTs. Subclinical myocardial dysfunction had not significantly improved at the 12-month follow-ups. (3) Conclusions: in patients recovered from COVID-19 pneumonia, left ventricular subclinical myocardial injury was related to cardiovascular risk factors and appeared stable during follow-up.

Non-invasive evaluation of pulmonary capillary wedge pressure using the left atrial expansion index in mitral valve stenosis, prosthesis and repair.

Pulmonary capillary wedge pressure (PCWP) non-invasive evaluation is limited in patients with mitral valve (MV) stenosis, prosthesis, and surgical repair. This study aimed to assess the left atrial expansion index (LAEI) measured through transthoracic echocardiography (TTE) as a novel parameter for estimating PCWP in these challenging cardiac conditions. We performed a retrospective, cross-sectional study, including chronic cardiac patients receiving within 24 h a clinically indicated right heart catheterization (RHC) and transthoracic echocardiographic (TTE) exam. PCWP measured during RHC was used as the reference. TTE measurements were performed offline, blinded to RHC results. LAEI was calculated as LAEI = [(LAmaxVolume-LAminVolume)/LAminVolume] × 100. We included 167 patients (age = 73 ± 11.5 years; PCWP = 18 ± 7.7 mmHg) with rheumatic mitral valve (MV) stenosis (16.2%), degenerative MV stenosis (51.2%), MV prosthesis (18.0%), and MV surgical repair (13.8%). LAEI correlated logarithmically with PCWP, and the log-transformed LAEI (lnLAEI) showed a good linear association with PCWP (r = - 0.616; p < 0.001). lnLAEI was an independent PCWP determinant, providing added predictive value over conventional clinical (age, atrial fibrillation, heart rate, MV subgroups) and echocardiographic variables (LVEF, MV effective orifice area, MV mean gradient, net atrioventricular compliance, and pulmonary arterial systolic pressure). lnLAEI identified PCWP > 12 mmHg with AUC = 0.870, p < 0.001; and PCWP > 15 mmHg with AUC = 0.797, p < 0.001, with an optimal cut-off of lnLAEI < 3.69. The derived equation PCWP = 36.8-5.5xlnLAEI estimated the invasively measured PCWP ± 6.1 mmHg. In this cohort of patients with MV stenosis, prosthesis, and surgical repair, lnLAEI resulted in a helpful echocardiographic parameter for PCWP estimation.

Incidence and mortality of infective endocarditis in the last decade: a single center study.

BACKGROUND: Infective endocarditis (IE) is a significant disease characterized by high mortality and complications. The aim of this study was to evaluate the incidence/100 000 inhabitants and the in-hospital mortality/100 000 inhabitants of IE during the last 10 years in the province of Ravenna. METHODS AND RESULTS: We reviewed the public hospitals discharge database from January 2010 to December 2020 using the international classification of disease codification (ICD-9) for IE. We used the Italian national statistical institute (ISTAT) archive to estimate the number of Ravenna inhabitants/year. In 10 years, we identified a total of 407 patients with diagnosis of IE.The incidence of IE increased significantly from 6.29 cases/100 000 inhabitants in 2010 to 19.58 cases/100 000 inhabitants in 2020 ( P  < 0.001). Also, the in-hospital mortality from IE increased over the same number of years, from 1.8 deaths/100 000 inhabitants in 2010 to 4.4 deaths/100 000 inhabitants in 2020 ( P  < 0.001). The mortality rate (%) of IE over the years did not increase ( P = 0.565). Also, over the years there was no difference in the site of infection ( P  = 0.372), irrespective of the valve localization or type, native valve ( P  = 0.347) or prosthetic valve ( P  = 0.145). On logistic regression analysis, age was the only predictor of in-hospital mortality (odds ratio 1.045, 95% confidence interval: 1.015; 1.075, P  = 0.003). CONCLUSIONS: Ravenna-based data on IE showed increased disease incidence but unchanged mortality rate over 10 years of follow-up. Age remains the sole predictor of population-based mortality, irrespective of the nature of the valve, native or substitute, and the organism detected on microbiology.

Combining echo-derived haemodynamic phenotypes and myocardial strain for risk stratification of chronic heart failure with reduced ejection fraction.

AIMS: Echocardiography has shown to categorize heart failure (HF) patients according to haemodynamic profiles. Whether left ventricular (LV) global longitudinal strain (LV-GLS) could integrate echo-derived haemodynamic profiles to risk stratify chronic HF patients is still unknown. METHODS AND RESULTS: Chronic HF outpatients with LV ejection fraction (LV-EF) <50% (n = 351) and LV-GLS assessment were evaluated and divided according to four haemodynamic phenotypes based on LV stroke volume index (SVI), LV filling pressure (LVFP), and right ventricular (RV) function: normal output-normal LVFP (NO-NP), normal output-high LVFP (NO-HP), low output-no RV dysfunction (LO-NRVD), and low output-RV dysfunction (LO-RVD). RV function was defined using the tricuspid annular plane systolic excursion and RV free-wall longitudinal strain. The median follow-up duration was 3.3 years. The combination of all-cause mortality and HF hospitalization was the primary endpoint. Secondary endpoints were all-cause mortality and cardiovascular mortality. The prevalence of NO-NP, NO-HP, LO-NRVD, and LO-RVD were 38%, 22%, 30%, and 10%, respectively. The haemodynamic model independently predicted primary and secondary outcomes, with incremental prognostic information over LV-EF (all P-values <0.001 for C-statistics). When univariate Cox regression analysis was performed to assess the prognostic stratification capability of LV-GLS in different haemodynamic subgroups, we observed a reduction in LV-GLS hazard ratios from the NO-NP to the LO-RVD for every endpoint. CONCLUSION: There was a continuum in LV-GLS impairment across the spectrum of haemodynamic phenotypes and its prognostic value resulted variable depending on the types of chronic HF patients. The highest prognostic information added by LV-GLS was in patients with normal SVI.

Severe Impairment of Left Ventricular Regional Strain in STEMI Patients Is Associated with Post-Infarct Remodeling.

Background: Measures of global left ventricular (LV) systolic function have limitations for the prediction of post-infarct LV remodeling (LVR). Therefore, we tested the association between a new measure of regional LV systolic function­the percentage of severely altered strain (%SAS)- and LVR after acute ST-elevation myocardial infarction (STEMI). As a secondary objective, we also evaluated the association between %SAS and clinical events during follow-up. Methods: Of 177 patients undergoing echocardiography within 24 h from primary percutaneous coronary angioplasty, 172 were studied for 3 months, 167 for 12 months, and 10 died. The %SAS was calculated by dividing the number of LV myocardial segments with ≥−5% peak systolic longitudinal strain by the total number of segments. LVR was defined as the increase in end-diastolic volume >20% at its first occurrence compared to baseline. Results: LVR percentage was 10.2% and 15.8% at 3 and 12 months, respectively. Based on univariable analysis, a number of clinical, laboratory, electrocardiographic and echocardiographic variables were associated with LVR. Based on multivariable analysis, %SAS and TnI peak remained associated with LVR (for %SAS 5% increase, OR 1.226, 95% CI 1.098−1.369, p < 0.0005; for TnI peak, OR 1.025, 95% CI 1.004−1.047, p = 0.022). %SAS and LVR were also associated with occurrence of clinical events at a median follow-up of 43 months (HR 1.02, 95% CI 1.0−1.04, p = 0.0165). Conclusions: In patients treated for acute STEMI, acute %SAS is associated with post-infarct LVR. Therefore, we suggest performing such evaluations on a routine basis to identify, as early as possible, STEMI patients at higher risk.

Added Value of CCTA-Derived Features to Predict MACEs in Stable Patients Undergoing Coronary Computed Tomography.

Clinical evidence has emphasized the importance of coronary plaques' characteristics, rather than lumen stenosis, for the outcome of cardiovascular events. Coronary computed tomographic angiography (CCTA) has a well-established role as a non-invasive tool for assessing plaques. The aim of this study was to compare clinical characteristics and CCTA-derived information of stable patients with non-severe plaques in predicting major adverse cardiac events (MACEs) during follow-up. We retrospectively selected 371 patients (64% male) who underwent CCTA in our center from March 2016 to January 2021 with Coronary Artery Disease­Reporting and Data System (CAD-RADS) 0 to 3. Of those, 198 patients (53% male) had CAD-RADS 0 to 1. Among them, 183 (49%) had normal pericoronary fat attenuation index (pFAI), while 15 (60% male) had pFAI ≥ 70.1 Hounsfield unit (HU). The remaining 173 patients (76% male) had CAD-RADS 2 to 3 and were divided into patients with at least one low attenuation plaque (LAP) and patients without LAPs (n-LAP). Compared to n-LAP, patients with LAPs had higher pFAI (p = 0.005) and had more plaques than patients with n-LAP. Presence of LAPs was significantly higher in elderly (p < 0.001), males (p < 0.001) and patients with traditional risk factors (hypertension p = 0.0001, hyperlipemia p = 0.0003, smoking p = 0.0003, diabetes p = <0.0001, familiarity p = 0.0007). Among patients with CAD-RADS 0 to 1, the ones with pFAI ≥ 70.1 HU were more often hyperlipidemic (p = 0.05) and smokers (p = 0.007). Follow-up (25,4 months, range: 17.6−39.2 months) demonstrated that LAP and pFAI ≥ 70.1 significantly and independently (p = 0.04) predisposed to outcomes (overall mortality and interventional procedures). There is an added value of CCTA-derived features in stratifying cardiovascular risk in low- to intermediate-risk patients with non-severe, non-calcified coronary plaques. This is of utmost clinical relevance as it is possible to identify a subset of patients with increased risk who need strengthening in therapeutic management and closer follow-up even in the absence of severe CAD. Further studies are needed to evaluate the effect of medical treatments on pericoronary inflammation and plaque composition.

Role of Cardiac Imaging Modalities in the Evaluation of COVID-19-Related Cardiomyopathy.

Cardiac involvement has been described during the course of SARS-CoV-2 disease (COVID-19), with different manifestations. Several series have reported only increased cardiac troponin without ventricular dysfunction, others the acute development of left or right ventricular dysfunction, and others myocarditis. Ventricular dysfunction can be of varying degrees and may recover completely in some cases. Generally, conventional echocardiography is used as a first approach to evaluate cardiac dysfunction in patients with COVID-19, but, in some cases, this approach may be silent and more advanced cardiac imaging techniques, such as myocardial strain imaging or cardiac magnetic resonance, are necessary to document alterations in cardiac structure or function. In this review we sought to discuss the information provided by different cardiac imaging techniques in patients with COVID-19, both in the acute phase of the disease and after discharge from hospital, and their diagnostic and prognostic role. We also aimed at verifying whether a specific form of cardiac disease due to the SARS-CoV-2 can be identified.

Noninvasive Evaluation of Intraventricular Flow Dynamics by the HyperDoppler Technique: First Application to Normal Subjects, Athletes, and Patients with Heart Failure.

Background: HyperDoppler is a new echocardiographic color Doppler-based technique that can assess intracardiac flow dynamics. The aim of this study was to verify the feasibility and reproducibility of this technique in unselected patients and its capability to differentiate measures of vortex flow within the left ventricle (LV) in normal sedentary subjects, athletes, and patients with heart failure. Methods: Two hundred unselected, consecutive patients presenting at the echocardiographic laboratory, 50 normal subjects, 30 athletes, and 50 patients with chronic heart failure and LV ejection fraction <50% were enrolled. Images were acquired using a MyLab X8 echo-scanner. Area, intensity, depth, length, and kinetic energy dissipation (KED) of vortex flow were measured. Results: The HyperDoppler technique feasibility was 94.5%. According to the intraclass correlation coefficient evaluations, repeatability and reproducibility of vortex flow measures were good for vortex area (0.82, 0.85), length (0.83, 0.82), and depth (0.87, 0.84) and excellent for intensity (0.92, 0.90) and KED (0.98, 0.98). Combining different vortex flow measures, the LV flow profile of healthy sedentary individuals, athletes, and heart failure patients could be differentiated. Conclusions: HyperDoppler is a feasible, reliable, and practical technique for the assessment of LV flow dynamics and may distinguish normal subjects and patients with heart failure.

Value of Left Ventricular Indexed Ejection Time to Characterize the Severity of Aortic Stenosis.

Aims: The assessment of aortic stenosis (AS) severity is still challenging, especially in abnormal hemodynamic conditions. Left ventricular ejection time (LVET) has been historically related to AS severity, but it also depends on heart rate (HR) and systolic function. Our aim was to verify if correcting LVET (LVET index, LVETI) by its determinants is helpful for the assessment of AS severity, irrespective of hemodynamic conditions. Methods and results: We retrospectively studied 152 patients with AS and 378 patients with heart failure and no-AS. At multivariate analysis, LVET (assessed with pulsed-wave Doppler) showed a strong correlation with stroke volume index (SVI) (Beta 0.354; p < 0.001), HR (−0.385; p < 0.001), AS grade (Beta 0.301; p < 0.001) and, less significantly, ejection fraction (LVEF) (Beta 0.108; p = 0.001). AS grade was confirmed to be a major determinant of LVET, irrespective of forward flow (assessed by SVI and transvalvular flow rate) and LVEF (above and below 50%). A regression equation was derived to index LVET (LVETI) to HR and SVI. By using this formula, LVETI detected severe AS more accurately (AUC 0.812, p < 0.001) than LVET alone (AUC 0.755, p for difference = 0.005). Similar results were observed in patients with abnormal flow status. As an exploratory finding, we observed that the highest tertile of LVETI was associated with a higher rate of aortic valve interventions during follow-up. Conclusions: LVETI correlates with AS severity better than uncorrected LVET, independently from hemodynamic conditions, and may help to discriminate severe AS. This finding needs confirmation in larger prospective multicenter studies.

Impact of the "atherosclerotic pabulum" on in-hospital mortality for SARS-CoV-2 infection. Is calcium score able to identify at-risk patients?

BACKGROUND: Although the primary cause of death in COVID-19 infection is respiratory failure, there is evidence that cardiac manifestations may contribute to overall mortality and can even be the primary cause of death. More importantly, it is recognized that COVID-19 is associated with a high incidence of thrombotic complications. HYPOTHESIS: Evaluate if the coronary artery calcium (CAC) score was useful to predict in-hospital (in-H) mortality in patients with COVID-19. Secondary end-points were needed for mechanical ventilation and intensive care unit admission. METHODS: Two-hundred eighty-four patients (63, 25 years, 67% male) with proven severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection who had a noncontrast chest computed tomography were analyzed for CAC score. Clinical and radiological data were retrieved. RESULTS: Patients with CAC had a higher inflammatory burden at admission (d-dimer, p = .002; C-reactive protein, p = .002; procalcitonin, p = .016) and a higher high-sensitive cardiac troponin I (HScTnI, p = <.001) at admission and at peak. While there was no association with presence of lung consolidation and ground-glass opacities, patients with CAC had higher incidence of bilateral infiltration (p = .043) and higher in-H mortality (p = .048). On the other side, peak HScTnI >200 ng/dl was a better determinant of all outcomes in both univariate (p = <.001) and multivariate analysis (p = <.001). CONCLUSION: The main finding of our research is that CAC was positively related to in-H mortality, but it did not completely identify all the population at risk of events in the setting of COVID-19 patients. This raises the possibility that other factors, including the presence of soft, unstable plaques, may have a role in adverse outcomes in SARS-CoV-2 infection.

Thyroid dysfunction on the heart: clinical effects, prognostic impact and management strategies.

Thyroid hormones have a considerable influence on cardiac function and structure. There are direct and indirect effects of thyroid hormone on the cardiovascular system, which are prominent in both hypothyroidism and hyperthyroidism. In this review, we discuss how thyroid dysfunction impacts cardiovascular pathophysiology and the underlying molecular mechanisms.