Massive Thrombosis of Mitral Bioprosthesis Due to SARS-CoV-2 Infection.

Thromboembolic events have been reported as frequent and fearsome complications in patients affected by SARS-CoV-2 infection. Patients undergoing cardiac valve replacement exhibit an increased risk of valve thrombosis, even with prosthetic biological valves, and especially in the first period after surgery. The management of these patients is challenging and requires prompt interventions. We report the case of a young woman infected by SARS-CoV-2 three months after double cardiac valve replacement that developed a massive prosthetic biological valve thrombosis despite optimal anticoagulant therapy.

Global Left Ventricular Myocardial Work Efficiency in Heart Failure Patients with Cardiac Amyloidosis: Pathophysiological Implications and Role in Differential Diagnosis.

INTRODUCTION: Cardiac amyloidosis (CA) is an infiltrative cardiomyopathy and a common cause of heart failure with preserved and mid-range ejection fraction (HFpEF and HFmrEF). Left ventricular (LV) systolic assessment is pivotal in differential diagnostic and prognostic stratification in CA. However, nondeformation and deformation-based parameters classically implied had many limitations. Myocardial work (MW) has been recently introduced for the evaluation of myocardial performance, in a load-independent fashion, in patients with cardiomyopathies. AIMS: This study aimed to evaluate MW parameters in LV performance assessment in CA and their possible role in differential diagnosis between AL and ATTR forms, compared with other echocardiographic parameters, also exploring the possible association between MW parameters and blood biomarkers. MATERIALS AND METHODS: The study population consisted of 25 patients with CA (10 with AL amyloidosis and 15 with wild-type ATTR [ATTRwt] form) and HFpEF or HFmrHF, enrolled between March 2018 and December 2019, undergoing a comprehensive clinical, biochemical, and imaging evaluation. Ten healthy individuals were studied as controls. ATTR patients had a noninvasive diagnosis of wtATTR-CA (positive 99mTc-hydroxy methylene-diphosphonate scintigraphy with a negative hematological screening), while AL patients underwent endomyocardial biopsy. All patients underwent standard transthoracic echocardiography. MW and related indices were estimated using a vendor-specific module. RESULTS: Compared to the ATTRwt group, patients in the AL group showed a more pronounced myocardial performance impairment assessed by Global Word Efficiency (GWE: 83.5% ± 6.3% vs. 88.2% ± 3.6%; P = 0.026). In multiple linear regression analysis, cardiac troponin I (Β = -0.55; P < 0.0001), global longitudinal strain (Β =0.35; P < 0.008), and regional relative strain ratio (Β = -0.30; P < 0.016) were significant predictors of GWE reduction in CA patients. At receiver operating characteristics curve analysis, among all other deformation-based and nondeformation-based echocardiographic parameters, GWE showed the highest area under the curve (AUC) (AUC 0.74; 95% CI: 0.55-0.96; P < 0.04). The optimal cutoff was determined by sensitivity/specificity analysis: a GWE < 86.5% identified patients with AL amyloidosis with a sensitivity and specificity, respectively, of 80.0% and 66.7%. CONCLUSIONS: The results of our pivotal study seem to highlight the importance of new deformation parameters to study myocardial performance in patients with CA, and to differentiate between AL CA and ATTR CA.

Two-Dimensional Transesophageal Echocardiography Assessment of the Major Aortic Annulus Diameter in Patients Undergoing Transcatheter Aortic Valve Replacement.

BACKGROUND: Multidetector computed tomography (MDCT) is the gold standard in annulus sizing before transcatheter aortic valve replacement (TAVR). However, MDCT has limited applicability in specific subgroups of patients, such as those with atrial fibrillation and chronic kidney disease. Two-dimensional transesophageal echocardiography (2DTEE) has traditionally been limited to the long-axis measurement of the anteroposterior diameter of the aortic annulus. We describe a new 2DTEE approach for the measurement of the major diameter of the aortic annulus. METHODS: Seventy-six patients with symptomatic severe aortic valve stenosis and high surgical risk underwent MDCT and 2DTEE before TAVR. A modified five-chamber view was used to measure the major aortic annulus diameter. This was obtained starting from a mid-esophageal four chamber and retracting the TEE probe up until the left ventricular outflow tract and the left and noncoronary aortic cusps were visualized: major aortic annulus diameter was measured as the distance between their insertion points in systole. RESULTS: Major aortic annulus diameters measured at 2DTEE showed good correlation with MDCT diameter (r = 0.79; P < 0.001) and perimeter (r = 0.87; P < 0.0001). Using factsheet-derived sizing criteria, 2DTEE alone would have allowed accurate sizing in 75% of patients, with 21% of oversizing predominantly with smaller annuli. CONCLUSIONS: We describe a new method for 2DTEE measurement of the major aortic annulus diameter; this approach is simple, correlates with MDCT, and allows adequate TAVR sizing in most patients. These findings may help in the assessment of patients with contraindications to or inadequate MDCT images.

Significant functional mitral regurgitation affects left atrial function in heart failure patients: haemodynamic correlations and prognostic implications.

AIMS: Functional mitral regurgitation (FMR) is a well-known pathophysiological factor in heart failure (HF) patients, and left atrial function (LAF) is a novel determinant of clinical status and outcome in this setting. However, little is known about the pathophysiological role of FMR on LAF in HFrEF patients. Aim of this study is to explore the possible interplay between the severity of FMR and LAF in heart failure with reduce ejection fraction (HFrEF) patients and their possible consequences. METHODS AND RESULTS: We studied 97 consecutive patients with FMR classified in two groups: mild-to-moderate MR ore less (FMR group, n = 38) and moderate-to-severe or more (SFMR group, n = 59). Using the phasic method, left atrial contractile, conduit, reservoir, and total emptying function (TLAEF) were calculated to assess LAF. SFMR group showed significantly lower values of LAF compared to FMR group. LA dysfunction (LA-dys) was defined for TLAEF values below the median and groups divided in four subgroups based on its presence. Patient with LA-Dys in SFMR group showed a worse clinical status, higher incidence of right ventricular dysfunction (RV-Dys), and pulmonary hypertension (PH), and a significant worse clinical survival compared to all other groups. CONCLUSION: In our study, the survival was significantly lower in SFMR/LA-Dys+ group. Furthermore, LA-Dys was strongly related with worse clinical status and higher incidence of PH and RV-Dys. These results suggest that in patients with SFMR and HFrEF, LA-Dys may represent both a marker of more advanced disease and a novel prognostic factor.

The mitral-to-aortic flow-velocity integral ratio in the real world echocardiographic evaluation of functional mitral regurgitation before and after percutaneous repair.

INTRODUCTION: Percutaneous mitral valve repair (PMVR) using MitraClip system has emerged as a therapeutic option for patients with functional severe mitral regurgitation (FMR) at prohibitive risk for surgery. In this setting, the echocardiographic assessment of FMR severity is challenging because the traditional echocardiographic methods have important limitations. The aim of this study was to assess the accuracy and reliability of a simple Doppler index, the mitral/aortic flow velocity integral ratio (MAVIR), to evaluate residual FMR severity after PMVR. METHODS: Eighty-five heart failure patients with functional MR and LV dysfunction (LVEF ≤ 40%) were included. FMR was quantified on the basis of traditional quantitative parameters of MR severity. MAVIR was expressed as the ratio of mitral and aortic time velocity integral (TVI) values. According to MR severity, 25 patients underwent MC implantation and at 6 months a complete echocardiographic follow-up was performed. RESULTS: A significant linear relationship was found between MAVIR and both VC and EROA. A MAVIR ≥1.02 identified pts with severe MR with a sensitivity of 86.7% and a specificity of 90.9%. At the 6 months echocardiographic follow-up after the MitraClip implantation, we observed a significant reduction of LAVI, LVED and LVES volume, while LVEF improved. Furthermore, MAVIR significantly decreased its decrease showed a significant linear relationship with LAVI reduction. CONCLUSION: Our data show a close relationship between MAVIR and traditional indexes of MR severity in patients with FMR. This Doppler-derived index seems applicable after PMVR where traditional echocardiographic index of MR severity shows significant limitations.

Tricuspid Annular Size and Regurgitation Progression After Surgical Repair for Degenerative Mitral Regurgitation.

The late worsening of nonsevere tricuspid regurgitation (TR) after mitral valve surgery is a relevant clinical problem that can lead to high-risk reoperation. Although tricuspid annulus (TA) dilatation has been proposed for prophylactic annuloplasty to prevent TR worsening, prospective data in degenerative mitral regurgitation (MR) are lacking. The aim of this prospective cohort study was to evaluate TA dimension to predict TR progression after valve repair for degenerative MR. Clinical and echocardiographic evaluation of 706 patients with degenerative MR and no significant TR was obtained preoperatively and at follow-up after isolated mitral valve repair. Together with standard cardiac chamber and valve analysis, 3-dimensional (3D) transesophageal echocardiography was performed to evaluate TA, including the anteroposterior and septolateral diameters. After a mean follow-up of 24 ± 15 months (range 6 to 60), 2 patients died while 14 developed severe MR. Compared with preoperative values, TR decreased (≤1 degree) in 227 patients, was unchanged in 437, and increased (≥1 degree) in 39 patients, with the development of significant TR (3 to 4 degree) in 3 patients. Receiver-operating characteristic curve analysis did not identify significant TA values predicting postoperative TR worsening. On multivariate regression analysis, recurrent MR and pulmonary hypertension at follow-up emerged as significant positive predictors of TR progression. Newly developed significant TR is a rare event after successful repair of degenerative MR. Although more accurate than conventional 2D measurement, 3D analysis of TA does not predict early to midterm subsequent TR progression.

Recoordination of opposing walls drives the response to cardiac resynchronization therapy: a longitudinal study using a strain discoordination index.

BACKGROUND AND AIMS: Intraventricular dyssynchrony has traditionally been studied by means of contraction delays between different myocardial segments. Recently, the discoordination of opposing wall contraction throughout the cardiac cycle has been proposed as a more faithful predictor of response. Aim of the current study was to evaluate which parameters - mechanical dyssynchrony or discoordination - normalize with left ventricular response to cardiac resynchronization therapy (CRT). METHODS: Cardiac mechanics were analysed before and after 6 months of CRT in 53 patients with left bundle branch block and advanced heart failure. Discoordination was quantified by means of the transverse strain discoordination index (TSDI) at basal and mid-ventricular segments; this index takes into account the percentage of time in the cardiac cycle in which cardiac deformation (transverse strain) of the two opposing walls occurs in noncoordinated directions. Dyssynchrony indices included septal to lateral peak-to-peak transverse strain delay and the standard deviation of time to peak tissue velocity in 12 mid-basal segments (Yu index). RESULTS: Around 63% of patients met the response criteria. Several baseline indices were predictive of reverse remodelling; TSDI at the mid-ventricular level demonstrated the best accuracy. Time from Q to peak velocity and strain tended to increase in all explored myocardial segments; despite a trend towards a decrease in septal-to-lateral strain delay, the latter decreased equally in responders and in nonresponding patients. Yu index decreased in responders more than in nonresponders, with borderline significance. Basal and medium TSDI remained unchanged in nonresponders and consistently normalized in patients who responded to CRT. The changes in TSDI were significantly correlated with improvements in left ventricular end-systolic volume and ejection fraction; the strongest correlation was observed for changes in TSDI measured at the mid-ventricular level. CONCLUSION: Left ventricular reverse remodelling after CRT is accompanied by the recoordination of opposite-wall contraction, as testified by changes in mid-ventricular TSDI, which also reveals as a very good predictor of response. On the contrary, changes of segmental peak-to-peak delays (dyssynchrony indices) fail to capture the complex nature of left ventricular response to CRT.

Dipyridamole coronary flow reserve stratifies prognosis in acute coronary syndrome patients without left anterior descending disease.

AIMS: Coronary flow reserve (CFR) assessment by transthoracic ultrasound of the left anterior descending (LAD) artery during dipyridamole stress echocardiography has been shown to predict prognosis in large unselected populations. Low values of CFR are strongly correlated with significant stenosis of the LAD; aim of the present study was to assess the prognostic impact of CFR in patients recovering from an acute coronary syndrome (ACS) with proven absence of LAD disease. METHODS: From an overall cohort of 325 patients with ACS who underwent a high-dose dipyridamole stress with combined assessment of CFR in the LAD and wall motion, 152 patients without LAD disease (stenosis <50%) were included in the present analysis; all subjects underwent coronary angiography and were subsequently monitored for the incidence of major cardiac events (MACE). RESULTS: After a median follow-up of 29 months, 22 patients developed MACE. Patients who experienced MACE differed from stable patients in terms of age, prevalence of diabetes, and CFR. Receiver-operating characteristic curve analysis defined a CFR <2.25 as the optimal cut point for prediction of MACE. Cox multivariable analysis for the prediction of MACE demonstrated independent predictive value only for CFR <2.25, smoking status, and number of stenotic vessels at angiogram. CONCLUSION: In high-risk patients with ACS, even in the absence of LAD disease, CFR significantly improves prediction of adverse events when added to standard evaluation. This finding supports a role of CFR in the risk stratification early after ACS and is in context with the concept that CFR reflects global atherosclerotic burden, endothelial dysfunction, and microvascular damage, more than just mirroring focal LAD disease.

A nutraceutical combination improves insulin sensitivity in patients with metabolic syndrome.

AIM: To test the efficacy of a proprietary nutraceutical combination in reducing insulin resistance associated with the metabolic syndrome (MetS). METHODS: Sixty-four patients with MetS followed at a tertiary outpatient clinic were randomly assigned to receive either placebo or a proprietary nutraceutical combination (AP) consisting of berberine, policosanol and red yeast rice, in a prospective, double-blind, placebo-controlled study. Evaluations were performed at baseline and after 18 wk of treatment. The homeostasis model assessment of insulin resistance (HOMA-IR) index was the primary outcome measure. Secondary endpoints included lipid panel, blood glucose and insulin fasting, after a standard mixed meal and after an oral glucose tolerance test (OGTT), flow-mediated dilation (FMD), and waist circumference. RESULTS: Fifty nine patients completed the study, 2 withdrew because of adverse effects. After 18 wk there was a significant reduction in the HOMA-IR index in the AP group compared with placebo (ΔHOMA respectively -0.6 ± 1.2 vs 0.4 ± 1.9; P < 0.05). Total and low density lipoprotein cholesterol also significantly decreased in the treatment arm compared with placebo (Δlow density lipoprotein cholesterol -0.82 ± 0.68 vs -0.13 ± 0.55 mmol/L; P < 0.001), while triglycerides, high density lipoprotein cholesterol, and the OGTT were not affected. In addition, there were significant reductions in blood glucose and insulin after the standard mixed meal, as well as an increase in FMD (ΔFMD 1.9 ± 4.2 vs 0 ± 1.9 %; P < 0.05) and a significant reduction in arterial systolic blood pressure in the AP arm. CONCLUSION: This short-term study shows that AP has relevant beneficial effects on insulin resistance and many other components of MetS.

Insulin resistance: Is it time for primary prevention?

Insulin resistance is a clinical condition characterized by a decrease in sensitivity and responsiveness to the metabolic actions of insulin, so that a given concentration of insulin produces a less-than-expected biological effect. As a result, higher levels of insulin are needed to maintain normal glucose tolerance. Hyperinsulinemia, indeed, is one of the principal characteristics of insulin resistance states. This feature is common in several pathologic conditions, such as type 2 diabetes, obesity, and dyslipidemia, and it is also a prominent component of hypertension, coronary heart disease, and atherosclerosis. The presence of endothelial dysfunction, related to insulin resistance, plays a key role in the development and progression of atherosclerosis in all of these disorders. Insulin resistance represents the earliest detectable abnormality in type 2 diabetes, and is one of the major underlying mechanisms of hypertension and cardiovascular diseases. Its early detection could be of great importance, in order to set a therapeutic attack and to counteract the higher risk of diabetes and cardiovascular diseases.

Response to pulmonary vasodilator treatment in a former smoker with combined interstitial lung disease complicated by pulmonary hypertension: case report and review of the literature.

We describe a 76-year-old former smoker with a diagnosis of combined pulmonary fibrosis and emphysema associated with pulmonary hypertension and rapidly progressive right heart failure, in whom combined treatment with sitaxsentan and sildenafil resulted in sustained improvement of his clinical condition and exercise performance, without any relevant adverse events. Combined pulmonary fibrosis and emphysema comprises a recently identified syndrome, probably related to tobacco use, and characterized by the coexistence of upper-lobe emphysema and fibrotic changes of the lower lobes, preserved lung volumes, significant hypoxemia, and a high prevalence of pulmonary hypertension, resulting in severe dyspnea. To date, no prospective series, to the best of our knowledge, has reported on the effects of pulmonary vasodilator therapy in such patients.

The importance of tricuspid regurgitation and right ventricular overload in ICD/CRT recipients: beside the left, beyond the left.

Device therapy for advanced heart failure has become increasingly employed in the last 10 years. Several retrospective studies have postulated a harmful effect of implantable cardioverter-defibrillator (ICD) lead placement on tricuspid valve function and right heart hemodynamics, in particular among patients with preexisting pulmonary vascular overload and both left and right ventricular remodeling/dysfunction. This functional hypothesis is also supported by long-term clinical follow-up analyses of ICD and cardiac resynchronization therapy recipients. In this viewpoint, we propose that the possibility of worsening tricuspid regurgitation and consequent hemodynamic deterioration following device implantation should be considered in future studies, as well as in the preimplant evaluation of individual candidates among other clinical factors.

Epoetin alfa increases frataxin production in Friedreich's ataxia without affecting hematocrit.

Objective of the study was to test the efficacy, safety, and tolerability of two single doses of Epoetin alfa in patients with Friedreich's ataxia. Ten patients were treated subcutaneously with 600 IU/kg for the first dose, and 3 months later with 1200 IU/kg. Epoetin alfa had no acute effect on frataxin, whereas a delayed and sustained increase in frataxin was evident at 3 months after the first dose (+35%; P < 0.05), and up to 6 months after the second dose (+54%; P < 0.001). The treatment was well tolerated and did not affect hematocrit, cardiac function, and neurological scale. Single high dose of Epoetin alfa can produce a considerably larger and sustained effect when compared with low doses and repeated administration schemes previously adopted. In addition, no hemoglobin increase was observed, and none of our patients required phlebotomy, indicating lack of erythropoietic effect of single high dose of erythropoietin.