Feasibility and value of two-dimensional volumetric stress echocardiography.

BACKGROUND: Stroke volume response during stress is a major determinant of functional status in heart failure and can be measured by two-dimensional (2-D) volumetric stress echocardiography (SE). The present study hypothesis is that SE may identify mechanisms underlying the change in stroke volume by measuring preload reserve through end-diastolic volume (EDV) and left ventricular contractile reserve (LVCR) with systolic blood pressure and end-systolic volume (ESV). METHODS: We enrolled 4735 patients (age 63.6±11.3 years, 2800 male) referred to SE for known or suspected coronary artery disease (CAD) and/or heart failure (HF) in 21 SE laboratories in 8 countries. In addition to regional wall motion abnormalities (RWMA), force was measured at rest and peak stress as the ratio of systolic blood pressure by cuff sphygmomanometer/ESV by 2D with Simpson's or linear method. Abnormal values of LVCR (peak/rest) based on force were ≤1.10 for dipyridamole (N.=1992 patients) and adenosine (N.=18); ≤2.0 for exercise (N.=2087) or dobutamine (N.=638). RESULTS: Force-based LVCR was obtained in all 4735 patients. Lack of stroke volume increase during stress was due to either abnormal LVCR and/or blunted preload reserve, and 57% of patients with abnormal LVCR nevertheless showed increase in stroke volume. CONCLUSIONS: Volumetric SE is highly feasible with all stresses, and more frequently impaired in presence of ischemic RWMA, absence of viability and reduced coronary flow velocity reserve. It identifies an altered stroke volume response due to reduced preload and/or contractile reserve.

Effect of Triple Combination Therapy With Lopinavir-Ritonavir, Azithromycin, and Hydroxychloroquine on QT Interval and Arrhythmic Risk in Hospitalized COVID-19 Patients.

INTRODUCTION: No data are provided about the effect of triple combination therapy with Lopinavir/Ritonavir (LPN/RTN), hydroxychloroquine (HQ) and azithromycin (AZT) on corrected QT (QTc) interval and arrhythmic risk, in COVID-19 patients. This study aims to describe the incidence of extreme QTc interval prolongation among COVID-19 patients on this experimental treatment and to identify the clinical features associated with extreme QTc prolongation. MATERIALS AND METHODS: Data of 87 COVID-19 patients, treated with triple combination including LPN/RTN, HQ and AZT, were analyzed. QT interval was obtained by the tangent method and corrected for heart rate using Bazett's formula. Extreme QTc interval prolongation was considered an absolute QTc interval ≥ 500 ms or an increase in QTc intervals of 60 ms or greater (ΔQTc ≥ 60 ms) compared with baseline. RESULTS: Hypertension (66.7%) and diabetes (25.3%) were the most prevalent cardiovascular comorbidities. Twenty patients (23%) showed extreme QTc interval prolongation; no clinical, electrocardiographic or pharmacological characteristics have been associated to extreme QTc prolongation, except the history of ischemic stroke (P= 0,007). One torsade de pointes (TdP) in patient with QTc extreme prolongation (QTc: 560 ms) after 5 days of therapy was recorded. CONCLUSIONS: We observed a high incidence of extreme QTc interval prolongation among COVID-19 patients on triple combination therapy. Since the incidence of malignant arrhythmias seems to be not negligible, a careful electrocardiographic monitoring would be advisable.

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.

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.

Clinical outcome in patients with intermediate stenosis of left anterior descending coronary artery after deferral of revascularization on the basis of noninvasive coronary flow reserve measurement.

BACKGROUND: Several reports suggest that noninvasive measurements of coronary flow reserve (CFR) by use of echocardiography may support decision making in intermediate stenosis of the left anterior descending coronary artery (LAD). The aim of the present study was therefore to analyze the clinical outcome in patients with intermediate stenosis of LAD after deferral of coronary revascularization on the basis of noninvasive CFR measurement. METHODS: the study population included 280 patients with intermediate LAD stenosis (50-70% by angiography) (62.2 +/- 9.6 years). All the patients underwent transthoracic CFR assessment of LAD (after dipyridamole infusion) within 2 weeks from coronary angiography. If CFR of LAD was < or = 2, PTCA was recommended; if CFR was > 2, medical treatment was chosen. Primary end points were cardiac death, myocardial infarction, coronary revascularization procedure, and unstable angina. RESULTS: mean follow-up was 43 +/- 11 months (range 12-52 months). In 150 patients (53.6%) (CFR < or = 2), coronary artery revascularization was performed (PTCA group); the remaining 130 patients (46.4%) (CFR > 2) were medically treated (medical group). Survival from cardiac death was 94% in the PTCA group and 92.4% in the medical group (P = 0.56). As for all cardiac events, the Kaplan-Meier percentage survival from cardiac events was 88.3% in the PTCA group and 86.4% in the medical group (P = 0.36). CONCLUSIONS: even if CFR as a "stand-alone" diagnostic criterion suffers from several structural limitations, a combined strategy including also other clinical and instrumental measurements before undergoing interventional procedures could improve the cost-benefit practice, in particular, for the management of patients with intermediate LAD stenosis.

Risk stratification and prognosis of patients with known or suspected coronary artery disease by use of supine bicycle exercise stress echocardiography.

BACKGROUND: The aim of this study was to assess the long-term predictive values of supine bicycle exercise stress echocardiography (ESE), and the ESE additional role compared to other traditional clinical and rest echocardiographic variables, in 607 patients with low, intermediate and high pretest risk of cardiac events. METHODS: Clinical status and long-term outcome were assessed for a mean period of 46 months (range 12-60 months). ESE was performed for the diagnosis of suspected coronary artery disease (CAD) in 267 patients (43.9%), and for risk stratification of known CAD in 340 patients (56.1%). At baseline, the mean value of wall motion score index (WMSI) was 1.22 +/- 0.36, and the mean left ventricular ejection fraction was 58.5 +/- 10.9%. RESULTS: ESE was positive for ischemia in 210 patients (34.9%), while ECG was suggestive for ischemia in 157 patients (25.8%). During the test only 97 patients (15.9%) experienced angina. At peak effort, the mean WMSI was 1.38 +/- 0.46. A low workload was achieved by 158 patients (26.1%). During the follow-up period there were 222 events, including 82 hard events (36.9%), 48 deaths (21.6%) and 34 acute non-fatal myocardial infarction (15.3%). At stepwise multivariate model, cigarette smoking (p < 0.01), peak WMSI (p < 0.001), ESE positive for ischemia (p < 0.001) and low workload (p < 0.01) were the only independent predictors of cardiac death, while positive ESE, peak WMSI, angina during the test and hypercholesterolemia were the only independent determinants of hard cardiac events. The cumulative 5-year mean survival rate according to ESE response was 95.9% in patients with negative ESE, and 83.7% in patients with positive ESE (log rank 13.6; p < 0.00001). CONCLUSIONS: ESE yields prognostic information in known or suspected CAD, especially in patients with intermediate pretest risk level. The combined evaluation of clinical variables and other ESE variables, such as peak WMSI and exercise capacity, may further select patients at greatest risk of cardiac death in the overall population.

Prognostic value of supine bicycle exercise stress echocardiography in patients with known or suspected coronary artery disease.

AIMS: To assess the prognostic significance of supine bicycle exercise stress echocardiography (ESE) for cardiac events, and the ESE additional role compared to other traditional clinical and echo variables, in patients with proven or suspected coronary artery disease (CAD). METHODS AND RESULTS: Clinical status and long-term outcome were assessed in 607 patients, for a mean period of 49.9 +/- 12.5 months. ESE was performed for the diagnosis of suspected CAD in 267 patients, and for the risk stratification in 340 patients. At baseline, the mean value of WMSI was 1.22 +/- 0.36, and the mean left ventricular ejection fraction was 58.2 +/- 10.9%. The ESE was positive for ischemia in 210 patients (34.9%), while the ECG was suggestive for ischemia in 157 patients. At peak effort, the mean WMSI was 1.38 +/- 0.46. Low work load was achieved by 158 patients (26.1%). During the follow-up period there were 222 events, including 48 cardiac deaths and 34 acute non-fatal myocardial infarction. By multivariable model, cigarette smoking, peak WMSI, positive ESE for ischemia and low work load were the only independent predictors of cardiac death. The cumulative 5-year mean survival rate according to ESE response was 95.9% in patients with negative ESE, and 81.7% in positive ESE (p < 0.00001). CONCLUSIONS: In patients with known or suspected CAD able to perform a physical stress, bicycle ESE is able to stratify patients at higher risk of cardiac events. The final report of an ESE performed for prognostic purpose should include both the assessment of induced dyssinergy and the evaluation of indexes of the extent and the severity of myocardial ischemia.

Noninvasive assessment of left and right internal mammary artery graft patency using transthoracic color Doppler echocardiography.

BACKGROUND: The aim of this study was to evaluate the patency of left and right internal mammary artery grafts respectively on the left anterior descending and right coronary artery by noninvasive transthoracic color Doppler echocardiography. METHODS: Thirty eight patients (34 males, 4 females, mean age 59 +/- 2 years), with a history of coronary artery bypass grafting for a total of 42 mammary artery grafts, were studied by means of color Doppler echocardiography at baseline and after vasodilation with dipyridamole infusion (0.56 mg/kg i.v. over 4 min). The evaluated echocardiographic parameters included: systolic (SPV) and diastolic peak velocities (DPV), systolic (SVI) and diastolic velocity-time integrals (DVI), and the DPV/SPV and DVI/SVI ratios. We also calculated the dipyridamole infusion to baseline ratio of the diastolic peak velocities (DPVdip/DPVbaseline), the index of internal mammary artery graft blood flow reserve and the percent DPV increment as an index of graft stenosis. RESULTS: On the basis of coronary angiography, two groups were selected: group A (36 mammary grafts) with patent grafts and group B (6 mammary grafts) with moderate or severe stenosis of the grafts. Group A had a predominant diastolic pattern with a DPV of 0.24 +/- 0.13 m/s, whereas group B had a predominant systolic pattern with a reduced DPV of 0.12 +/- 0.03 m/s (p < 0.01). Dipyridamole induced an increase in the DPV respectively of 86.8 +/- 64.4% in group A and 13.8 +/- 15.9% in group B (p < 0.001). Statistical analysis (Mann-Whitney test) revealed a significant difference between the two groups for the baseline DPV (p < 0.01), DVI (p < 0.05), DPV/SPV ratio (p < 0.005), DVI/SVI ratio (p < 0.05), and for the after dipyridamole infusion values: DPV (p < 0.0001), DVI (p < 0.005), DPV/SPV ratio (p < 0.001), and DVI/SVI ratio (p < 0.05). Multivariate analysis showed that the percent DPV increment, the DPVdip/DPVbaseline ratio and the baseline DPV were independent determinants of the stenosis as evaluated at angiography (beta = -0.38, p < 0.01; beta = -0.37, p < 0.01, and beta = -0.33, p < 0.05, respectively; cumulative r2 = 0.25, standard error 0.30 m/s, p < 0.005). CONCLUSIONS: The echocardiographic evaluation of the mammary grafts is a simple, noninvasive method for the assessment of the graft patency and of the functional status of the vessel. The percent DPV increment and baseline DPV were independent determinants of mammary graft stenosis.

[Mitral stenosis: echocardiographic evaluation]. / Stenosi mitralica: valutazione ecocardiografica.

The diagnostic tools available for the evaluation of mitral stenosis are two-dimensional and Doppler echocardiography, which are able to identify morphologic and flow changes. Two-dimensional echocardiography can be used to assess the morphological appearance of the mitral valve apparatus, including its mobility and thickness and the presence of calcified leaflets and subvalvular fusion. Wilkins'score permits evaluation of each variable which, on the basis of its severity, is scored according to a point system ranging from 1 to 4. In patients with severe mitral stenosis, a low total score (< 8) and elastic symmetric commissures suggest valvuloplasty. A total score > 10 and the presence of more than mild mitral regurgitation or of calcification of both commissures suggest valvular replacement. The left atrial and ventricular chamber sizes and other associated valvular diseases can also be assessed at two-dimensional or Doppler echocardiography. The severity of obstruction can be assessed using two-dimensional and Doppler echocardiographic area (pressure half-time, proximal isovelocity surface area, continuity equation) and with the mean transmitral gradient measured using a continuous wave Doppler signal across the mitral valve. Valvuloplasty can also be performed in patients with a high score when surgery is contraindicated. During follow-up it is necessary to evaluate the area, the mean gradient, the right ventricular systolic pressure and the presence of a residual atrial septal defect and mitral regurgitation. Restenosis is diagnosed when the valve area decreases to 50% of that achieved during valvuloplasty or surgery.