Prognostic value of right ventricular longitudinal strain in patients with secondary mitral regurgitation undergoing transcatheter edge-to-edge mitral valve repair.

AIMS: To evaluate the prognostic impact of pre-procedural right ventricular longitudinal strain (RVLS) in patients with secondary mitral regurgitation (SMR) undergoing transcatheter edge-to-edge repair (TEER) in comparison with conventional echocardiographic parameters of RV function. METHODS AND RESULTS: This is a retrospective study including 142 patients with SMR undergoing TEER at two Italian centres. At 1-year follow-up 45 patients reached the composite endpoint of all-cause death or heart failure hospitalization. The best cut-off value of RV free-wall longitudinal strain (RVFWLS) to predict outcome was -18% [sensitivity 72%, specificity of 71%, area under curve (AUC) 0.78, P < 0.001], whereas the best cut-off value of RV global longitudinal strain (RVGLS) was -15% (sensitivity 56%, specificity 76%, AUC 0.69, P < 0.001). Prognostic performance was suboptimal for tricuspid annular plane systolic excursion, Doppler tissue imaging-derived tricuspid lateral annular systolic velocity and fractional area change (FAC). Cumulative survival free from events was lower in patients with RVFWLS ≥ -18% vs. RVFWLS < -18% (44.0% vs. 85.4%; < 0.001) as well as in patients with RVGLS ≥ -15% vs. RVGLS < -15% (54.9% vs. 81.7%; P < 0.001). At multivariable analysis FAC, RVGLS and RVFWLS were independent predictors of events. The identified cut-off of RVFWLS and RVGLS both resulted independently associated with outcomes. CONCLUSION: RVLS is a useful and reliable tool to identify patients with SMR undergoing TEER at high risk of mortality and HF hospitalization, on top of other clinical and echocardiographic parameters, with RVFWLS offering the best prognostic performance.

Effect of Chronic Kidney Disease on 5-Year Outcome in Patients With Heart Failure and Secondary Mitral Regurgitation Undergoing Percutaneous MitraClip Insertion.

Chronic kidney disease (CKD) is strongly related to outcomes in cardiovascular diseases. Limited data are available regarding the independent prognostic role of CKD after transcatheter mitral valve repair with MitraClip. We sought to evaluate the real impact of CKD in a large series of patients with heart failure (HF) and secondary mitral regurgitation (SMR) who underwent MitraClip treatment. The study included 565 patients with severe SMR from a multicenter international registry. Patients were stratified into 3 groups according to estimated glomerular filtration rate (eGFR) assessment before MitraClip implantation: normal eGFR (≥60 ml/min/1.73 m2) (n = 196), mild-to-moderate CKD (30 to 59 ml/min/1.73 m2) (n = 267), and severe CKD (<30 ml/min/1.73 m2) (n = 102). The primary end point was a composite of overall death and the first rehospitalization for HF, the secondary end points were overall death, cardiac death, and first rehospitalization for HF. CKD was present in about 2/3 of patients. At 5-year Kaplan-Meier analysis, primary clinical end point occurred in 60% of patients with normal eGFR, compared with 73% cases in patients with mild-to-moderate CKD and 91% in patients with severe CKD (p <0.001). Long-term overall death rate significantly decreased with increasing eGFR, and cardiac death and rehospitalization for HF rates. Multivariate Cox regression analysis identified severe CKD as the strongest independent predictor of adverse outcome (hazard ratio 2.136, 95% confidence interval 1.164 to 3.918, p = 0.014). In conclusion, CKD affected about 2/3 of patients who underwent MitraClip treatment for severe SMR, and it was a strong and independent predictor of 5-year adverse outcomes.

Subclinical myocardial dysfunction in patients recovered from COVID-19.

BACKGROUND: Myocardial injury (MI) can be detected during the acute phase of Coronavirus disease 19 (COVID-19) and is associated with a dismal prognosis. Recent imaging studies described the persistence of cardiac abnormalities after the recovery. The aim of the study was to investigate the spectrum of cardiac abnormalities at mid-term follow-up in patients recovered from COVID-19 using clinical assessment, laboratory tests, and imaging evaluation with comprehensive echocardiography. METHODS: This is an observational, cross-sectional study assessing an unselected cohort of consecutive patients recovered from COVID-19. MI was defined by elevated plasma levels of high sensitive troponin T (hsTnT). At the follow-up, a complete examination including echocardiography was performed. RESULTS: The 123 patients included were divided into two groups according to the presence of MI during hospitalization: group A (without MI) and group B (with MI). After a median of 85 days, group B patients were more frequently symptomatic for dyspnea and had significantly higher values of hsTnT and N-Terminal prohormone of Brain Natriuretic Peptide (NT-proBNP), compared to Group A. No differences between the two groups in left nor right ventricle dimension and ejection fraction were found. However, in group B a significant reduction of mean left ventricle global longitudinal strain was observed (-15.7±.7 vs -18.1± .3 in group A, p < 0.001), together with higher frequency of impaired diastolic function and higher values of pulmonary pressure. CONCLUSIONS: In patients recovered from COVID-19, echocardiography with speckle-tracking analysis may be an useful imaging tool to identify subclinical myocardial dysfunction and potentially guide management strategies.

COVID-19 and Heart Failure: From Epidemiology During the Pandemic to Myocardial Injury, Myocarditis, and Heart Failure Sequelae.

A close and intriguing relationship has been suggested between heart failure (HF) and coronavirus disease 2019 (COVID-19). First, COVID-19 pandemic represented a global public health emergency in the last year and had a catastrophic impact on health systems worldwide. Several studies showed a reduction in HF hospitalizations, ranging from 30 to 66% in different countries and leading to a subsequent increase in HF mortality. Second, pre-existing HF is a risk factor for a more severe clinical course of COVID-19 and an independent predictor of in-hospital mortality. Third, patients hospitalized for COVID-19 may develop both an acute decompensation of chronic HF and de-novo HF as a consequence of myocardial injury and cardiovascular (CV) complications. Myocardial injury occurred in at least 10% of unselected COVID-19 cases and up to 41% in critically ill patients or in those with concomitant CV comorbidities. Few cases of COVID-19-related acute myocarditis, presenting with severe reduction in the left ventricular (LV) ejection fraction and peculiar histopathological findings, were described. However, recent data suggested that COVID-19 may be associated with both systolic and diastolic LV dysfunction, with LV diastolic impairment, pulmonary hypertension, and right ventricular dysfunction representing the most frequent findings in echocardiographic studies. An overview of available data and the potential mechanisms behind myocardial injury, possibly leading to HF, will be presented in this review. Beyond the acute phase, HF as a possible long-term consequence of cardiac involvement in COVID-19 patients has been supposed and need to be investigated yet.

Percutaneous Edge-to-Edge Mitral Valve Repair: Beyond the Left Heart.

Right ventricular (RV) dysfunction and tricuspid regurgitation (TR) are known to be associated with adverse outcomes in patients undergoing percutaneous mitral valve repair (PMVR). Although the effect of PMVR on left ventricular function is well known, data on the response of the right ventricle to PMVR, and its impact on prognosis, are limited. In this review the authors summarize available data regarding the prognostic role of RV function and TR in PMVR recipients and the possible effects of PMVR on the right heart. Preprocedural tricuspid annular plane systolic excursion < 15 mm, tricuspid annular tissue Doppler S' velocity < 9.5 cm/sec, and moderate or severe TR are reported as predictors of adverse outcome after PMVR. Therefore, they should be carefully evaluated for patient selection. Moreover, emerging data show that the benefit of PMVR may go beyond the left heart, leading to an improvement in RV function and a reduction in TR severity. Among PMVR recipients, improvement in RV function and reduction of TR degree are observed mainly in patients with RV dysfunction at baseline. On the other hand, high postprocedural transmitral pressure gradients seem to be associated with lack of RV reverse remodeling. Timing of mitral intervention with respect to RV impairment and predictors of RV reverse remodeling after PMVR are unknown. Further studies are needed to fill these gaps in evidence.

Myocardial Involvement in COVID-19: an Interaction Between Comorbidities and Heart Failure with Preserved Ejection Fraction. A Further Indication of the Role of Inflammation.

PURPOSE OF THE REVIEW: Coronavirus Disease 2019 (COVID-19) and cardiovascular (CV) disease have a close relationship that emerged from the earliest reports. The aim of this review is to show the possible associations between COVID-19 and heart failure (HF) with preserved ejection fraction (HFpEF). RECENT FINDINGS: In hospitalized patients with COVID-19, the prevalence of HFpEF is high, ranging from 4 to 16%, probably due to the shared cardio-metabolic risk profile. Indeed, comorbidities including hypertension, diabetes, obesity and chronic kidney disease - known predictors of a severe course of COVID-19 - are major causes of HFpEF, too. COVID-19 may represent a precipitating factor leading to acute decompensation of HF in patients with known HFpEF and in those with subclinical diastolic dysfunction, which becomes overt. COVID-19 may also directly or indirectly affect the heart. In otherwise healthy patients, echocardiographic studies showed that the majority of COVID-19 patients present diastolic (rather than systolic) impairment, pulmonary hypertension and right ventricular dysfunction. Such abnormalities are observed both in the acute or subacute phase of COVID-19. Cardiac magnetic resonance reveals myocardial inflammation and fibrosis in up to the 78% of patients in the chronic phase of the disease. These findings suggest that COVID-19 might be a novel independent risk factor for the development of HFpEF, through the activation of a systemic pro-inflammatory state. Follow-up studies are urgently needed to better understand long-term sequelae of COVID-19 inflammatory cardiomyopathy.

Prognostic Value of Pre-operative Atrial Fibrillation in Patients With Secondary Mitral Regurgitation Undergoing MitraClip Implantation.

Limited data are available regarding the independent prognostic role of preoperative atrial fibrillation (AF) after transcatheter mitral valve repair with MitraClip. We sought to evaluate the impact of preoperative AF in patients with heart failure (HF) and concomitant secondary mitral regurgitation (MR) after MitraClip treatment. The study included 605 patients with significant secondary MR from a multicenter international registry. Patients were stratified into 2 groups according to the presence or absence of preoperative AF. Primary end point was 5-year overall death, secondary end points were 5-year cardiac death and first re-hospitalization for HF. To account for baseline differences, patients were propensity score matched 1:1. The overall prevalence of preoperative AF was 44%. At 5-year Kaplan-Meier analysis, compared with patients without AF, those with AF had significantly more adverse events in term of overall death (67% vs 43%; HR 1.84, log-rank p <0.001) and cardiac death (56% vs 29%; HR 2.11, log-rank p <0.001) and re-hospitalization for HF (63% vs 52%; HR 1.33, log-rank p = 0.048). Multivariate analysis identified AF as independent predictor of worse outcome in term of primary end point (HR 1.729, 95% C.I. 1.060 to 2.821; p = 0.028). After propensity score matching, patients with AF had higher rates of death and cardiac mortality but similar rates of re-hospitalization for HF. In conclusion, in patients with HF undergoing MitraClip treatment for secondary MR, preoperative AF is common and an unfavourable predictor of 5-year death and cardiac death. However, AF did not affect the frequency of re-hospitalization for HF.

Impact of COVID-2019 outbreak on prevalence, clinical presentation and outcomes of ST-elevation myocardial infarction.

AIMS: The aim of this study was to report the prevalence, clinical features and outcomes of patients with ST-elevation myocardial infarction (STEMI) hospitalized during the Corona-Virus Disease 2019 (COVID-19) outbreak compared with those admitted in a previous equivalent period. METHODS AND RESULTS: Eighty-five patients admitted for STEMI at a high-volume Italian centre were included. Patients hospitalized during the COVID-19 outbreak (21 February-10 April 2020) (40%) were compared with those admitted in pre-COVID-19 period (3 January-20 February 2020) (60%). A 43% reduction in STEMI admissions was observed during the COVID-19 outbreak compared with the previous period. Time from symptom onset to first medical contact (FMC) and time from FMC to primary percutaneous coronary intervention (PPCI) were longer in patients admitted during the COVID-19 period compared with before [148 (79-781) versus 130 (30-185) min; P = 0.018, and 75 (59-148)] versus 45 (30-70) min; P < 0.001]. High-sensitive troponin T levels on admission were also higher. In-hospital mortality was 12% in the COVID-19 phase versus 6% in the pre-COVID-19 period. Incidence of the composite end-point, including free-wall rupture, severe left ventricular dysfunction, left ventricular aneurysm, severe mitral regurgitation and pericardial effusion, was higher during the COVID-19 than the pre-COVID-19 period (19.6 versus 41.2%; P = 0.030; odds ratio = 2.87; 95% confidence interval 1.09-7.58). CONCLUSION: The COVID-19 pandemic had a significant impact on the STEMI care system reducing hospital admissions and prolonging revascularization time. This translated into a worse patient prognosis due to more STEMI complications.

Coronavirus disease 2019 and cardiovascular implications.

: The coronavirus disease 2019 (COVID-19) has important implications for the cardiovascular care of patients. COVID-19 interacts with the cardiovascular system on multiple levels, increasing morbidity in patients with underlying cardiovascular conditions and favoring acute myocardial injury and dysfunction. COVID-19 infection may also have long-term implications for overall cardiovascular health. Many issues regarding the involvement of the cardiovascular system remain controversial. Despite angiotensin-converting enzyme 2 serving as the site of entry of the virus into the cells, the role of angiotensin-converting enzyme inhibitors or AT1 blockers requires further investigation. Therapies under investigation for COVID-19 may have cardiovascular side effects. Treatment of COVID-19, especially the use of antivirals, must be closely monitored. This article is a review of the most updated literature.

Lung ultrasound-guided therapy reduces acute decompensation events in chronic heart failure.

OBJECTIVE: Pulmonary congestion is the main cause of hospital admission in patients with heart failure (HF). Lung ultrasound (LUS) is a useful tool to identify subclinical pulmonary congestion. We evaluated the usefulness of LUS in addition to physical examination (PE) in the management of outpatients with HF. METHODS: In this randomised multicentre unblinded study, patients with chronic HF and optimised medical therapy were randomised in two groups: 'PE+LUS' group undergoing PE and LUS and 'PE only' group. Diuretic therapy was modified according to LUS findings and PE, respectively. The primary endpoint was the reduction in hospitalisation rate for acute decompensated heart failure (ADHF) at 90-day follow-up. Secondary endpoints were reduction in NT-proBNP, quality-of-life test (QLT) and cardiac mortality at 90-day follow-up. RESULTS: A total of 244 patients with chronic HF and optimised medical therapy were enrolled and randomised in 'PE+LUS' group undergoing PE and LUS, and in 'PE only' group. Thirty-seven primary outcome events occurred. The hospitalisation for ADHF at 90 day was significantly reduced in 'PE+LUS' group (9.4% vs 21.4% in 'PE only' group; relative risk=0.44; 95% CI 0.23 to 0.84; p=0.01), with a reduction of risk for hospitalisation for ADHF by 56% (p=0.01) and a number needed to treat of 8.4 patients (95% CI 4.8 to 34.3). At day 90, NT-proBNP and QLT score were significantly reduced in 'PE+LUS' group, whereas in 'PE only' group both were increased. There were no differences in mortality between the two groups. CONCLUSIONS: LUS-guided management reduces hospitalisation for ADHF at mid-term follow-up in outpatients with chronic HF.

Characteristics and outcomes of patients hospitalized for COVID-19 and cardiac disease in Northern Italy.

AIMS: To compare demographic characteristics, clinical presentation, and outcomes of patients with and without concomitant cardiac disease, hospitalized for COVID-19 in Brescia, Lombardy, Italy. METHODS AND RESULTS: The study population includes 99 consecutive patients with COVID-19 pneumonia admitted to our hospital between 4 March and 25 March 2020. Fifty-three patients with a history of cardiac disease were compared with 46 without cardiac disease. Among cardiac patients, 40% had a history of heart failure, 36% had atrial fibrillation, and 30% had coronary artery disease. Mean age was 67 ± 12 years, and 80 (81%) patients were males. No differences were found between cardiac and non-cardiac patients except for higher values of serum creatinine, N-terminal probrain natriuretic peptide, and high sensitivity troponin T in cardiac patients. During hospitalization, 26% patients died, 15% developed thrombo-embolic events, 19% had acute respiratory distress syndrome, and 6% had septic shock. Mortality was higher in patients with cardiac disease compared with the others (36% vs. 15%, log-rank P = 0.019; relative risk 2.35; 95% confidence interval 1.08-5.09). The rate of thrombo-embolic events and septic shock during the hospitalization was also higher in cardiac patients (23% vs. 6% and 11% vs. 0%, respectively). CONCLUSIONS: Hospitalized patients with concomitant cardiac disease and COVID-19 have an extremely poor prognosis compared with subjects without a history of cardiac disease, with higher mortality, thrombo-embolic events, and septic shock rates.

COVID-19 and heart failure: from infection to inflammation and angiotensin II stimulation. Searching for evidence from a new disease.

Patients with cardiovascular disease and, namely, heart failure are more susceptible to coronavirus disease 2019 (COVID-19) and have a more severe clinical course once infected. Heart failure and myocardial damage, shown by increased troponin plasma levels, occur in at least 10% of patients hospitalized for COVID-19 with higher percentages, 25% to 35% or more, when patients critically ill or with concomitant cardiac disease are considered. Myocardial injury may be elicited by multiple mechanisms, including those occurring with all severe infections, such as fever, tachycardia, adrenergic stimulation, as well as those caused by an exaggerated inflammatory response, endotheliitis and, in some cases, myocarditis that have been shown in patients with COVID-19. A key role may be that of the renin-angiotensin-aldosterone system. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects human cells binding to angiotensin-converting enzyme 2 (ACE2), an enzyme responsible for the cleavage of angiotensin II into angiotensin 1-7, which has vasodilating and anti-inflammatory effects. Virus-mediated down-regulation of ACE2 may increase angiotensin II stimulation and contribute to the deleterious hyper-inflammatory reaction of COVID-19. On the other hand, ACE2 may be up-regulated in patients with cardiac disease and treated with ACE inhibitors or angiotensin receptor blockers. ACE2 up-regulation may increase the susceptibility to COVID-19 but may be also protective vs. angiotensin II-mediated vasoconstriction and inflammatory activation. Recent data show the lack of untoward effects of ACE inhibitors or angiotensin receptor blockers for COVID-19 infection and severity. Prospective trials are needed to ascertain whether these drugs may have protective effects.

Cardiac Involvement in a Patient With Coronavirus Disease 2019 (COVID-19).

Importance: Virus infection has been widely described as one of the most common causes of myocarditis. However, less is known about the cardiac involvement as a complication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Objective: To describe the presentation of acute myocardial inflammation in a patient with coronavirus disease 2019 (COVID-19) who recovered from the influenzalike syndrome and developed fatigue and signs and symptoms of heart failure a week after upper respiratory tract symptoms. Design, Setting, and Participant: This case report describes an otherwise healthy 53-year-old woman who tested positive for COVID-19 and was admitted to the cardiac care unit in March 2020 for acute myopericarditis with systolic dysfunction, confirmed on cardiac magnetic resonance imaging, the week after onset of fever and dry cough due to COVID-19. The patient did not show any respiratory involvement during the clinical course. Exposure: Cardiac involvement with COVID-19. Main Outcomes and Measures: Detection of cardiac involvement with an increase in levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) and high-sensitivity troponin T, echocardiography changes, and diffuse biventricular myocardial edema and late gadolinium enhancement on cardiac magnetic resonance imaging. Results: An otherwise healthy 53-year-old white woman presented to the emergency department with severe fatigue. She described fever and dry cough the week before. She was afebrile but hypotensive; electrocardiography showed diffuse ST elevation, and elevated high-sensitivity troponin T and NT-proBNP levels were detected. Findings on chest radiography were normal. There was no evidence of obstructive coronary disease on coronary angiography. Based on the COVID-19 outbreak, a nasopharyngeal swab was performed, with a positive result for SARS-CoV-2 on real-time reverse transcriptase-polymerase chain reaction assay. Cardiac magnetic resonance imaging showed increased wall thickness with diffuse biventricular hypokinesis, especially in the apical segments, and severe left ventricular dysfunction (left ventricular ejection fraction of 35%). Short tau inversion recovery and T2-mapping sequences showed marked biventricular myocardial interstitial edema, and there was also diffuse late gadolinium enhancement involving the entire biventricular wall. There was a circumferential pericardial effusion that was most notable around the right cardiac chambers. These findings were all consistent with acute myopericarditis. She was treated with dobutamine, antiviral drugs (lopinavir/ritonavir), steroids, chloroquine, and medical treatment for heart failure, with progressive clinical and instrumental stabilization. Conclusions and Relevance: This case highlights cardiac involvement as a complication associated with COVID-19, even without symptoms and signs of interstitial pneumonia.

Accuracy and reproducibility of aortic annular measurements obtained from echocardiographic 3D manual and semi-automated software analyses in patients referred for transcatheter aortic valve implantation: implication for prosthesis size selection.

Aims: A 3D transoesophageal echocardiography (3D-TOE) reconstruction tool has recently been introduced. The system automatically configures a geometric model of the aortic root and performs quantitative analysis of these structures. We compared the measurements of the aortic annulus (AA) obtained by semi-automated 3D-TOE quantitative software and manual analysis vs. multislice computed tomography (MSCT) ones. Methods and results: One hundred and seventy-five patients (mean age 81.3 ± 6.3 years, 77 men) who underwent both MSCT and 3D-TOE for annulus assessment before transcatheter aortic valve implantation were analysed. Hypothetical prosthetic valve sizing was evaluated using the 3D manual, semi-automated measurements using manufacturer-recommended CT-based sizing algorithm as gold standard. Good correlation between 3D-TOE methods vs. MSCT measurements was found, but the semi-automated analysis demonstrated slightly better correlations for AA major diameter (r = 0.89), perimeter (r = 0.89), and area (r = 0.85) (all P < 0.0001) than manual one. Both 3D methods underestimated the MSCT measurements, but semi-automated measurements showed narrower limits of agreement and lesser bias than manual measurements for most of AA parameters. On average, 3D-TOE semi-automated major diameter, area, and perimeter underestimated the respective MSCT measurements by 7.4%, 3.5%, and 4.4%, respectively, whereas minor diameter was overestimated by 0.3%. Moderate agreement for valve sizing for both 3D-TOE techniques was found: Kappa agreement 0.5 for both semi-automated and manual analysis. Interobserver and intraobserver agreements for the AA measurements were excellent for both techniques (intraclass correlation coefficients for all parameters >0.80). Conclusion: The 3D-TOE semi-automated analysis of AA is feasible and reliable and can be used in clinical practice as an alternative to MSCT for AA assessment.

Echocardiographic features of post-transcatheter aortic valve implantation thrombosis and endocarditis.

BACKGROUND: Transcatheter heart valve thrombosis (THV-t) and endocarditis (THV-e) are relevant complications after transcatheter aortic valve implantation (TAVI). Transcatheter heart valve (THV) dysfunction definition is mostly based on Doppler (stenosis/regurgitation) without considering leaflets characteristics. PURPOSE: To evaluate the additional diagnostic value of leaflets echocardiographic features over Doppler when prosthetic valve complication is suspected. METHODS: Among 621 post-TAVI patients, 128 cases with probable valve complication were identified. THV-t was finally diagnosed in 13 patients (10%) and THV-e in 8 (6%), while the remaining 107 (84%) had no definitive diagnosis of thrombosis/endocarditis (THV-no). We analyzed at 2 time points (baseline and follow-up) both traditional Doppler parameters and leaflets morpho-functional features. RESULTS: Both Doppler and leaflets parameters showed high sensitivity (sensitivity 92%) and low specificity (ranging from specificity 32% to 74%) in detecting THV-t. Interestingly, the combination of mean aortic pressure gradient ≥20 mm Hg and leaflet thickening significantly improved the specificity of echocardiography for diagnosis of THV thrombosis (specificity 94%). On the other hand, echocardiographic diagnosis of THV endocarditis remained limited by very low sensitivity despite showing high specificity. CONCLUSIONS: The combination of Doppler and leaflets parameters can improve the echocardiographic diagnosis of THV thrombosis in post-TAVI patients with suspicious symptoms, via a significant increase in the overall test specificity. This would potentially allow more rational gatekeeping to more expensive/invasive diagnostic examinations (eg, CT scan) or therapeutic trials (eg, unnecessary anticoagulation).