Cardiac amyloidosis: A survey of current awareness, diagnostic modalities, treatment practices, and clinical challenges among cardiologists in selected Middle Eastern countries.

BACKGROUND: Cardiac amyloidosis (CA) is a chronic progressive disease caused by the deposition of amyloid fibrils in cardiac tissues. Diagnosis and management of CA are complicated and have developed over the years. HYPOTHESIS: Middle Eastern countries have significant knowledge disparities in diagnosing, managing, and treating different subtypes of CA. METHODS: An online survey was sent to cardiologists in four countries (Saudi Arabia, Lebanon, Egypt, and Iraq) interested in heart failure and practicing for more than a year. The survey questioned the characteristics of the participants and their institutions. It addressed their knowledge and practices in CA specifically diagnostic modalities, treatment options, and interest in education and knowledge exchange. RESULTS: A total of 85 physicians participated in the survey. There was a variation in the participating cardiologists' knowledge, experience level, and readiness of their institutes to manage patients with ATTR-CM. Most participants believed that a high rate of ATTR-CM misdiagnosis existed. Participants' knowledge of the diagnostic modalities and "red flags" raising suspicion about ATTR-CM varied. Another challenge was the availability of essential diagnostic modalities among various cardiology centers. A knowledge gap was also observed regarding updates in ATTR-CM management. However, there was a high endorsement of the need for more education, physician networking, and knowledge exchange. CONCLUSIONS: This survey highlighted the need for increasing awareness levels among cardiologists in the four selected Middle Eastern countries. Cardiologists are most likely to benefit from additional training and knowledge exchange on the latest management advances of this disease. Thus, measures must be taken to focus on the physician's awareness of ATTR-CM patient journey to achieve a better quality of care and outcome.

Ultrasound Imaging of the Superior Vena Cava: A State-of-the-Art Review.

Greater interest in imaging the superior vena cava (SVC) in recent years has arisen because of increased focus on disorders of the right heart; the growing use of transvenous access lines, dialysis catheters, and device leads; and the emergence of right ventricular mechanical circulatory support systems via the transcatheter approach. As a low-pressure venous conduit in the right upper mediastinum, the SVC is prone to compression by various pathologic processes, to invasion by malignancies originating in nearby structures, and to complications arising from intraluminal device leads and indwelling catheters. Computed tomography and magnetic resonance venography are the modalities of choice for structural imaging of the SVC. Ultrasound allows a reasonable, yet less detailed anatomic assessment of this venous conduit. Spectral and color Doppler imaging by ultrasound are the most valuable noninvasive tools for the interrogation of SVC blood flow, a marker of the filling pattern of the right heart. Analysis of the velocity, duration, and direction of the Doppler waveforms and their phasic response to respiration makes it possible to distinguish normal from abnormal flow patterns and offers diagnostic insights into disorders that affect right heart function. The aims of this review are to demonstrate the added value SVC imaging provides during transthoracic and transesophageal echocardiographic studies, to outline its usefulness for the detection and evaluation of structural abnormalities, and to detail the role of spectral Doppler imaging in aiding the diagnosis of various disorders that affect the right heart.

Does Secondary Antibiotic Prophylaxis Improve Clinical Outcomes in Adult Rheumatic Heart Disease Patients Post-Valve Replacement?

BACKGROUND: Secondary prevention of recurrent rheumatic fever in individuals with rheumatic heart disease (RHD) requires continuous antibiotic prophylaxis. However, the impact of antibiotic prophylaxis on the outcome of patients with severe RHD who underwent heart valve replacement is unknown. The objective of the study was to assess the relationship between the use of antibiotics as secondary prophylaxis in RHD patients who underwent valve replacement and clinical outcomes including mortality, reoperation, and valve-related hospitalization. METHODS: We retrospectively compared outcomes of adult patients who underwent heart valve replacement for RHD at our institution from 1990 through 2014 and who received secondary antibiotic prophylaxis (prophylaxis group) with those who did not receive prophylaxis (nonprophylaxis group) using propensity score matching analysis. RESULTS: A total of 1094 patients (56% females, median age 40 years, range 31-53 years) were included with a median follow-up of 9.6 years (range 2.9-12.6 years). Antibiotic prophylaxis was prescribed in 201 patients (18%). Propensity score matching analysis demonstrated no significant difference in overall survival (95% [92%-98%] vs 97% [95%-99%], respectively; P = .7), valve-related hospitalization-independent survival (72% [range 65%-78%] vs 81% [range 76%-88%]; P = .25), and redo valve surgery-independent survival [76% [range 70%-83%] vs 75% [range 72%-79%]; P = .41) at 10-year follow-up in the nonantibiotic prophylaxis versus the antibiotic prophylaxis group. CONCLUSION: Secondary antibiotic prophylaxis among adult RHD patients following valve replacement is not associated with improved clinical outcomes.

Treatment of amyloid light chain cardiac amyloidosis: systematic review and future directions.

BACKGROUND: Several treatment strategies for amyloid light chain cardiac amyloidosis (AL-CA) have been described in the literature; however, there is no consensus about the optimal approach to AL-CA. OBJECTIVE: We conducted this systematic review to summarize current evidence from published studies about the safety and efficacy of various treatment regimens for patients with AL-CA, mainly focusing on autologous stem cell transplant (ASCT) and heart transplant. METHODS: An electronic literature search of PubMed, Web of Science, Scopus, EBSCO, and CINAHL Plus was conducted through December 2019 using the relevant keywords and prespecified MeSH terminology. Records were screened, and eligible studies were selected and narratively discussed. Data on the hematologic and cardiac responses as well as the safety of the treatment regimens were extracted and synthesized narratively in the context of the systematic review. RESULTS: Thirty published articles were included in this systematic review. The most commonly used first-line treatment in the included studies was bortezomib-based therapy followed by high-dose melphalan and ASCT, with recent evidence of improved outcome with the addition of daratumumab. Heart transplant was found to extend survival for selected patients who were not eligible for ASCT; however, it was found to affect the patients' tolerance of further chemotherapy in some studies. Published data on longterm outcomes with immunomodulatory agents were scarce. CONCLUSION: Current evidence suggests several possible regimens for the treatment of AL-CA. Effective treatment approaches for AL-CA include induction therapy with bortezomib-based or immunotherapy-based combinations in moderate/severe forms of cardiac involvement, followed by high-dose melphalan and ASCT in eligible patients, and heart transplant for selected severe cases. Therefore, we highlight the necessity of conducting well-designed, randomized controlled trials to provide evidence about the efficacy of these drugs with respect to ASCT.

Describing mode of death in three major cardiac amyloidosis subtypes to improve management and survival.

BACKGROUND: The three main cardiac amyloidosis (CA) types have different progression and prognosis. Little is known about the mode of death (MOD) which is commonly attributed to cardiovascular causes in CA. Improving MOD's knowledge could allow to adapt patient care. OBJECTIVE: This retrospective study describes the MOD that occurred during long-term follow-up in CA patients in light-chain (AL), transthyretin hereditary (ATTRv) or wild-type (ATTRwt). MATERIAL AND METHODS: Patients referred to and cared for, at the French referral centre for CA, Henri Mondor Hospital, Créteil between 2010 and 2016 were included. Clinical information surrounding patient deaths were investigated and centrally evaluated by two blinded clinical committees which classified MOD as cardiovascular, non-cardiovascular or unknown and sub-classified it depending on its subtype. RESULTS: From the 566 patients included, 187 had AL, 206 ATTRv and 173 ATTRwt. During the 864 patient-year follow-up, 160 (28%) deaths occurred, with median survival time of 17.3 months (interquartile range 5.1-35.4). The most frequent MOD was cardiovascular (64%) of which worsening heart failure occurred most frequently and for which, 69% were of AL subtype, 79% ATTRv and 76% ATTRwt. Sudden death also occurred more frequently in AL subtype accounting for 29% of AL deaths. Non-cardiovascular MOD occurred in 26% of patients overall. Among these, infection was the most common non-cardiovascular MOD in any type of CA (80%). CONCLUSIONS: Mortality is high during natural course of CA and differs between subtypes. The main MOD were worsening heart failure, sudden death and infection, opening room to optimise management.

Multiparametric Approach for the Assessment of Mechanical Prosthetic Tricuspid Leaflet Function.

BACKGROUND: There is a lack of comprehensive echocardiographic data to allow discrimination of normal versus abnormal mechanical prosthetic tricuspid valve (MPTV) leaflet function. The identification of such parameters is essential to optimize diagnostic and therapeutic measures. METHODS: The authors investigated bileaflet MPTV function by comparing transthoracic echocardiographic data from 21 episodes of leaflet dysfunction due to valve thrombosis in 12 patients with data from 56 individuals with normal MPTV function. All episodes of dysfunction were confirmed by transesophageal echocardiography and/or cine fluoroscopy. Transthoracic echocardiography-derived two-dimensional, color, and spectral Doppler variables, including MPTV peak early diastolic velocity (E velocity), mean gradient, pressure half-time, time-velocity integral (TVI) of the MPTV, ratio of TVIMPTV to TVI of the left ventricular outflow tract (LVOT) and TVI of the right ventricular outflow tract (RVOT), and continuity-derived effective orifice area, were measured in both groups. RESULTS: Most episodes of MPTV dysfunction resulted from simultaneous involvement of both leaflets (57%), with leaflet(s) often immobilized in the open or semiopen position (71%). Transthoracic and transesophageal echocardiography performed similarly in detecting abnormal leaflet motion (90% vs 88%, P = .68), whereas transesophageal echocardiography was better in identifying MPTV thrombosis (31% vs 14%, respectively, P = .01). Color Doppler demonstrated flow propagation abnormalities in 67% of episodes of leaflet dysfunction but not in the control group (P < .0001). Doppler variables associated with MPTV leaflet dysfunction included E velocity > 1.6 m/sec, mean gradient > 5 mm Hg, PHT > 157 msec, TVIMPTV > 42 cm, TVIMPTV/TVILVOT > 2.3, TVIMPTV/TVIRVOT > 3.0, and continuity-derived effective orifice area ≤ 1.1 cm2, with most variables showing high and similar accuracy (area under the curve ≥ 95%). CONCLUSIONS: This study represents the first comprehensive echocardiographic assessment of MPTV leaflet dysfunction that provides parameters and criteria to distinguish normal versus abnormal prosthetic valve function.

Using the Appropriate Formula for QT Measurement Can Save Lives.

CDK 4/6 inhibitors, in combination with endocrine therapy, are the standard of care for patients with endocrinesensitive advanced breast cancer. This class of drug, however, is associated with QT prolongation, which serves as a surrogate marker for Torsades de Pointes (TdP), a cause of life-threatening ventricular arrhythmias and sudden cardiac death. The ICH E14 guidance document uses the Bazett formula for reporting of cardio-dynamic and safety ECG data in clinical trials. While there is substantial familiarity with the Bazett (QTcB) formula (QT/(RR) 1/2), the Fridericia (QTcF) formula (QT/(RR) 1/3 ) is preferred in the cancer population as it is often more accurate at heart rate extreme. Accordingly, the Fridericia formula is currently the standard adopted by the FDA when submitting QT data for review. At the King Faisal Specialist Hospital and Research Center, a total of 82 patients with advanced breast cancer, had a baseline ECG on day 1 before the initiation of ribociclib based therapy. Of the enrolled 82 patients, 19 (23%) were initially excluded from receiving ribociclib based due to a prolonged QTc >450ms, however, when the QTc-interval was manually measured and recalculated using Fridericia and Framingham formulae using MDCalC (https://www.mdcalc.com),17 of 19 patients successfully received their treatment without any arrhythmogenic effects. Repeat ECG on day14, and day 1 of cycle 2 demonstrated that none of these patients had QTc exceeding 480 ms. Our data highlights the complexities of evaluating the QT interval in oncology patients and the utility of the Fridericia/Framingham formulae in this population. Given these findings, we recommend the adoption of the Fridericia or Framingham formulae for measurement of QTc in all cancer patients exposed to potentially QT-prolonging cancer therapy.

Echocardiographic Patterns of Left Ventricular Diastolic Function in Cardiac Amyloidosis: An Updated Evaluation.

AIMS: Multimodal imaging has allowed cardiac amyloidosis (CA) to be increasingly recognised as a treatable cause of heart failure with preserved ejection fraction, but its prognosis remains poor due to late diagnosis. To assess the left ventricular diastolic function (LVDF) patterns in a large contemporary CA cohort according to the current recommendations and to identify their determinants. METHODS AND RESULTS: We conducted a monocentric, observational study on a cohort of CA patients from a tertiary CA referral centre. Diastolic function was analysed using standard echocardiography and clinical, laboratory and survival parameters were collected. Four hundred and sixty-four patients with one of the three main type of CA were included: 41% had grade III diastolic dysfunction (restrictive mitral pattern), 25% had grade II diastolic dysfunction, and 25% had grade I diastolic dysfunction; 9% were unclassified. No difference was found between the main CA types. After multivariate analyses, grades II and III were independently associated with dyspnoea, elevated NT-proBNP, cardiac infiltration and systolic dysfunction (global longitudinal strain). Grade I patients had a better prognosis. CONCLUSIONS: All LVDF patterns can be observed in CA. One quarter of CA patients have grade I LVDF, reflecting the emergence of earlier stage-related phenotypes with a better prognosis.

Constrictive pericarditis following heart transplantation: Reality or fiction?

Constrictive pericarditis (CP) is a curable cause of diastolic heart failure with prior cardiac surgery being a recognizable etiology. We report a patient who developed CP one year following heart transplantation. Several clinical and imaging related factors may lead to diagnostic delays in similar patients, including the mistaken belief that transplanted hearts are devoid of pericardium and thus do not develop constriction. Post-transplantation pericardial effusion, mediastinitis, and cardiac rejection predispose to future CP. Caretakers should consider this entity in allograft recipients who develop heart failure symptoms of unclear etiology.

Established and candidate transthyretin amyloidosis variants identified in the Saudi population by data mining.

BACKGROUND: Familial transthyretin (TTR) amyloidosis (ATTR) is an autosomal dominant disease with significant phenotypic heterogeneity. Its prevalence in Saudi Arabia has not previously been investigated. An existing exome variant database of Saudi individuals, sequenced to globally investigate rare diseases in the population, was mined for TTR variants and filtered for missense mutations resulting in single amino acid changes. A total of 13,906 Saudi exomes from unrelated individuals were analyzed blindly. RESULTS: Three TTR variants known to be associated with ATTR amyloidosis were identified. Additionally, three novel TTR mutations were identified. Structural analysis of the three novel variants suggests that at least two could be amyloidogenic. The most common variant associated with amyloidosis was p.Val142Ile (allele frequency 0.001). Further investigation of these variants and their translation to clinical practice may help to diagnose, monitor, and manage patients with ATTR amyloidosis. CONCLUSION: Multiple TTR variants potentially associated with systemic ATTR amyloidosis were identified in the Saudi population. Early diagnosis and intervention, facilitated by familial genetic testing of patients with ATTR amyloidosis, may benefit in the management of this disease. Early diagnosis could be enhanced through inclusion of ATTR variants in existing population-based screening programs.

Ultrasound Imaging of the Abdominal Aorta: A Comprehensive Review.

Ultrasound is the imaging modality of choice for the initial evaluation of disorders that involve the abdominal aorta (AA). The diagnostic value of ultrasound resides in its ability to allow assessment of the anatomy and structure of the AA using two- dimensional, three-dimensional, and contrast-enhanced imaging. Moreover, ultrasound permits evaluation of the physiologic and hemodynamic consequences of abnormalities through Doppler interrogation of blood flow, thus enabling the identification and quantification of disorders within the AA and beyond its boundaries. The approach to ultrasound imaging of the AA varies, depending on the purpose of the study and whether it is performed in a radiology or vascular laboratory or in an echocardiography laboratory. The aim of this review is to demonstrate the usefulness of ultrasound imaging for the detection and evaluation of disorders that involve the AA, detail the abnormalities that are detected or further assessed, and outline its value for echocardiographers, sonographers, and radiologists.

Atrial function in the Fontan circulation: comparison with invasively assessed systemic ventricular filling pressure.

Abnormal atrial mechanics in biventricular circulations have been associated with elevated left heart filling pressures. Similar associations in the Fontan circulation are unknown. The aim of this study was to examine the relationship between atrial mechanics and invasively assessed hemodynamic parameters late after the Fontan operation. Thirty-nine Fontan patients with echocardiographic and invasive hemodynamic studies done within 48 h were included and were compared to 40 age-matched healthy controls. Atrial and ventricular strain measurements were measured offline using 2-dimensional speckle-tracking. Mean age was 10.2 ± 6.7 years and 24 (62%) were male. Atrial strain measures were lower in Fontan patients compared to healthy controls. There was no significant association between atrial strain measurements and Fontan systemic ventricular filling pressures (SVFP) as indicated by pulmonary artery occlusion pressures, direct left atrial pressure or systemic ventricular end-diastolic pressure. Global atrial strain was not correlated with segmental atrial strain in the pulmonary venous atrium. Global atrial reservoir strain was positively correlated with pulmonary vascular resistance (r = 0.508, p = 0.045). Global atrial conduit strain was positively correlated with E/A ratio of the AV valve inflow (r = 0.555, p = 0.002). Atrial and ventricular strain measurements were not significantly correlated. In patients with a Fontan, global atrial function is significantly depressed, and is uncoupled from segmental left lateral atrial function. Global as well as segmental atrial mechanics are not significantly associated with SVFPs in Fontan patients. Instead, global atrial reservoir function appears to parallel pulmonary vascular resistance.

Spectral Doppler Interrogation of the Pulmonary Veins for the Diagnosis of Cardiac Disorders: A Comprehensive Review.

Data obtained from echocardiographic studies are used on a daily basis to guide clinical decision-making regarding patient management and the need for additional diagnostic investigations. Interrogation of blood flow in the pulmonary veins by spectral, most often pulsed-wave, Doppler is an important component of any comprehensive echocardiographic study. Whereas it is most often used to help assess left-sided filling pressure and quantify the severity of mitral regurgitation, the pulmonary vein Doppler profile provides added diagnostic insights into several disorders that affect heart function and allows assessment of their hemodynamic consequences on the heart. The aim of this review is to summarize current knowledge in the field of PV Doppler interrogation, highlight the physiological and pathological parameters that influence it, and delineate the manifestations of various cardiovascular disorders on the flow profile.

Diagnostic Accuracy of Dobutamine Stress Echocardiography for Detection of Cardiac Allograft Vasculopathy in Orthotopic Heart Transplant Patients.

OBJECTIVE: Cardiac allograft vasculopathy is one of the leading causes of late graft failure and subsequent death in orthotopic heart transplant. Although invasive coronary angiography is the gold standard modality for detection of cardiac allograft vasculopathy, dobutamine stress echocardiography has been recently frequently used as an alternative. Our aim was to evaluate the diagnostic performance of dobutamine stress echocardiography for detection of cardiac allograft vasculopathy in transplant patients. METHODS: A retrospective analysis was conducted using a total of 150 dobutamine stress echocardiographic exams that were performed on 99 patients in our institution, with paired coronary angiogram and no acute rejection, within a median of 538 [interquartile range 371-816] days. Sensitivity and specificity of dobutamine echocardiography to detect allograft vasculopathy was evaluated. Allograft vasculopathy was defined as Grade 1 or higher based on ISHLT criteria. A positive dobutamine stress echo result was defined by new or worsening wall motion abnormality. RESULTS: Median age of the population at transplant was 34 [interquartile range 22-46] years; 76 (77%) patients were male. Allograft vasculopathy was present in 31 (20.6%) out of 150 coronary angiograms. Only 7 (4.6%) of that number were positive on dobutamine stress echocardiography. Sensitivity and specificity for allograft vasculopathy detection was 3% and 94%, respectively. Out of 7 false positive dobutamine stress echocardiograms, two were in patients with myocardial bridging. Two patients with mild acute rejection had both negative dobutamine stress echo. CONCLUSIONS: Overall, positivity of dobutamine stress echocardiography in patients after heart transplant is low. It has high specificity, but very low sensitivity for detection of cardiac allograft vasculopathy. Dobutamine stress echocardiography should only be cautiously used as an alternative to coronary angiography.

Which echocardiographic parameters improve the risk prediction for peri-operative outcomes in patients undergoing coronary bypass surgery: a prospective study.

OBJECTIVE: To assess the performance of transthoracic echocardiographic parameters to predict operative mortality and morbidity in patients undergoing coronary artery bypass grafting, and to assess its incremental prognostic value as compared to the Society of Thoracic Surgeons (STS) score. MATERIALS AND METHODS: We prospectively collected the clinical and biological data required to calculate the STS score in patients hospitalised for coronary artery bypass grafting. Preoperative transthoracic echocardiography was performed for each patient. The primary endpoint was 30-day mortality or major morbidity (i.e. stroke, renal failure, prolonged ventilation, deep sternal wound infection, reoperation) as defined by the STS. The secondary endpoint was prolonged hospitalisation for over 14 days. RESULTS: A total of 172 patients was included (mean age 66.1±10.2 years, 12.2% were women). The primary endpoint occurred in 33 patients (19.2%), and 28 patients (16.3%) had a prolonged hospital stay. Independent predictive factors for the primary endpoint were an increased left atrial volume (>31 mL/m²; odds ratio (OR) 3.55, 95% confidence interval (CI) 1.38-9.12; P=0.004) and a decreased tricuspid annular plane systolic excursion (<20 mm; OR 3.45, 95% CI 1.47-8.21; P=0.008). The predictive value of the multivariate model increased when the two echocardiographic parameters were added to the STS score (area under the curve 0.598 vs. 0.695, P=0.001; integrated discrimination improvement 7.44%). CONCLUSION: In patients undergoing coronary artery bypass grafting, preoperative assessment of left atrial size and tricuspid annular plane systolic excursion should be performed systematically, as it provides additional prognostic information to the STS score.