The Role of New Imaging Technologies in the Diagnosis of Cardiac Amyloidosis.

Cardiac amyloidosis is an infiltrative disorder caused by transthyretin or immunoglobulin free light-chain deposition, which determines clinical disease with similar phenotype but different time course, prognosis and therapy. Multimodality imaging is the cornerstone for disease diagnosis and management. Multimodality imaging has revolutionized the approach to the disease favoring its awareness and simplifying its diagnosis, especially in ATTR cardiac amyloidosis. This describes the different imaging tools, from the traditional to the more novel ones, and highlights the different approach in each different setting (prognosis, subtyping, prognosis, monitoring disease progression, and response to 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.

Network Medicine: A Clinical Approach for Precision Medicine and Personalized Therapy in Coronary Heart Disease.

Early identification of coronary atherosclerotic pathogenic mechanisms is useful for predicting the risk of coronary heart disease (CHD) and future cardiac events. Epigenome changes may clarify a significant fraction of this "missing hereditability", thus offering novel potential biomarkers for prevention and care of CHD. The rapidly growing disciplines of systems biology and network science are now poised to meet the fields of precision medicine and personalized therapy. Network medicine integrates standard clinical recording and non-invasive, advanced cardiac imaging tools with epigenetics into deep learning for in-depth CHD molecular phenotyping. This approach could potentially explore developing novel drugs from natural compounds (i.e. polyphenols, folic acid) and repurposing current drugs, such as statins and metformin. Several clinical trials have exploited epigenetic tags and epigenetic sensitive drugs both in primary and secondary prevention. Due to their stability in plasma and easiness of detection, many ongoing clinical trials are focused on the evaluation of circulating miRNAs (e.g. miR-8059 and miR-320a) in blood, in association with imaging parameters such as coronary calcifications and stenosis degree detected by coronary computed tomography angiography (CCTA), or functional parameters provided by FFR/CT and PET/CT. Although epigenetic modifications have also been prioritized through network based approaches, the whole set of molecular interactions (interactome) in CHD is still under investigation for primary prevention strategies.

Transcatheter Aortic Valve Replacement and Cardiac Resynchronization Therapy in Cancer-Related Cardiotoxicity.

Cardiotoxicity related to antineoplastic agents is a rising and growing issue, therefore early recognition and prompt management can impact on the overall prognosis of cancer patients. We report the case of a 70-year-old woman without cardiovascular risk factors, with a medical history of non-Hodgkin lymphoma and chronic myeloid leukemia treated with chemotherapy and radiotherapy, who underwent transcatheter aortic valve replacement for severe aortic stenosis and cardiac resynchronization therapy for further development of complete left bundle branch block, with a significant improvement of her functional status and left ventricle systolic function in a long-term follow-up.

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.

Right atrial mass following transcatheter radiofrequency ablation for recurrent atrial fibrillation: thrombus, endocarditis or mixoma?

We report a case of an asymptomatic patient in whom a right atrial mass was fortuitously documented by echocardiography few months after a transcatheter radiofrequency catheter ablation for recurrent AF. No masses were seen in the cardiac chambers before the ablative procedure, raising important diagnostic and decision-making issues. The patient was referred to the surgeon and a diagnosis of right atrial myxoma was made.

Right ventricular myocardial function in patients with either idiopathic or ischemic dilated cardiomyopathy without clinical sign of right heart failure: effects of cardiac resynchronization therapy.

OBJECTIVE: In dilated cardiomyopathy (DCM), right ventricular (RV) dysfunction has been reported and attributed both to altered loading conditions and to RV involvement in the myopathic process. The aim of the study was to detect RV myocardial function in DCM using two-dimensional (2D) strain echocardiography and to assess the effects of cardiac resynchronization therapy (CRT) on RV myocardial strain during a 6-month follow-up. METHODS AND RESULTS: A total of 110 patients (mean age: 55.4 +/- 11.2 years) with either idiopathic (n = 60) or ischemic (n = 50) DCM, without overt clinical signs of RV failure, underwent standard echo and 2D strain analysis of RV longitudinal strain in RV septal and lateral walls. The two groups were comparable for clinical variables (New York Heart Association class III in 81.8%). Left ventricular volumes, ejection fraction, stroke volume, and mitral valve effective regurgitant orifice were similar between the two groups. No significant differences were evidenced in Doppler mitral and tricuspid inflow measurements. RV diameters were mildly increased in patients with idiopathic DCM, while RV tricuspid annulus systolic excursion and Tei-index were comparable between the two groups. RV global longitudinal strain and regional peak myocardial strain were significantly impaired in patients with idiopathic DCM compared with those having ischemic DCM (all P < 0.001). Using left ventricular end-systolic volume as marker for response to CRT, 70 patients (63.3%) were long-term responders. Ischemic DCM patient responders to CRT showed a significant improvement in RV peak systolic strain. Conversely, in patients with idiopathic DCM and in ischemic patients nonresponders to CRT, no improvement in RV function was evidenced. By multivariable analysis, in the overall population, ischemic etiology of DCM (P < 0.0001), positive response to CRT (P < 0.001), and longitudinal intraventricular dyssynchrony (P <0.01) emerged as the only independent determinants of RV global longitudinal strain after CRT. CONCLUSIONS: Two-dimensional strain represents a promising noninvasive technique to assess RV myocardial function in patients with DCM. RV myocardial deformation at baseline and after CRT are more impaired in idiopathic compared with ischemic DCM patients. Future longitudinal studies are warranted to understand the natural history of RV myocardial function, the extent of reversibility of RV dysfunction with CRT, and the possible prognostic impact of such indexes in patients with congestive heart failure.

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.

[Amyloid cardiomyopathy: a link between cardiology and hematology. A case report of positive response to standard therapy]. / La cardiomiopatia amiloidotica: un'interfaccia fra cardiologia ed ematologia. Descrizione di un caso clinico con risposta favorevole alla terapia tradizionale.

Cardiac involvement in primary systemic amyloidosis, due to amassing of fragments of light chains, is detected in the majority of cases. We report the case of a 56-year-old woman who came to our observation because of symptoms of congestive heart failure. Diagnosis of restrictive cardiomyopathy was made by echocardiographic examination, which showed right ventricular hypertrophy, disarray of interventricular septum and restrictive flow pattern at the mitral valve. Primary systemic amyloidosis was diagnosed by abdominal fat pad biopsy. Laboratory findings confirmed biopsy results, leading to the definite diagnosis of restrictive cardiomyopathy due to IgA kappa monoclonal gammopathy in primary systemic amyloidosis.

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.

Transthoracic Doppler echocardiography of mammary artery grafts to assess graft function.

BACKGROUND: Transthoracic Doppler echocardiography of internal mammary artery grafts (MAGs) has been tested by the supraclavicular approach, but little information is available about the parasternal approach. OBJECTIVE: To evaluate the usefulness of parasternal transthoracic Doppler echocardiography to assess the patency of left and right MAGs. PATIENTS AND METHODS: Forty-eight patients with previous MAGs were divided into two groups on the basis of coronary angiography: 42 patients had patent MAGs and six patients had severe MAG stenosis. Doppler echocardiography of MAGs was performed on all patients, both at baseline and after low-dose dipyridamole infusion. Systolic and diastolic time-velocity integrals and their ratios were obtained, and MAG flow reserve was calculated. RESULTS: Patients with patent MAGs had a predominant diastolic flow, while a prominent systolic pattern was found in the presence of MAG stenosis. In patients with stenosis, baseline Doppler analysis showed a lower diastolic peak velocity (DPV) (P<0.01), diastolic time-velocity integral (P<0.05), and diastolic and systolic time-velocity integral ratios (both P<0.005), and a reduced MAG flow reserve (P<0.001). In the overall population, when adjusting for clinical variables, a multilinear regression analyis underscored MAG flow reserve (beta=0.38, P<0.01) and baseline DPV (beta=0.29, P<0.05) as independent determinants of MAG stenosis (cumulative R2=0.25, P<0.005). CONCLUSIONS: Doppler echocardiographic evaluation of MAGs is a reliable, noninvasive tool to assess MAG patency and functional status of the vessel. MAG blood flow reserve and baseline DPV are independent determinants of MAG stenosis.

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.