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.

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.

Echocardiography in Pulmonary Arterial Hypertension.

PURPOSE OF REVIEW: Pulmonary arterial hypertension (PAH) is a devastating disease which can result in right heart (RH) failure and death. Herein, we discuss the current clinical applications of echocardiography in PAH. RECENT FINDINGS: Advanced echocardiographic techniques (strain, strain rate, 2D-speckle tracking strain, and three-dimensional echocardiography) may reveal in the near future additional important insights into RH structure and function. Although right-heart catheterization is mandatory for a definitive diagnosis, echocardiography (resting and exercise) represents a key noninvasive imaging test on the diagnostic-prognostic-therapeutic PAH algorithm.

Aspergillus flavus native valve endocarditis following combined liver and renal transplantation: Case report and review of the literature.

Aspergillus endocarditis is a rare infection that occurs most commonly in patients with prior cardiac surgery but cases in post-transplant recipients without prior cardiac surgery have been reported. Diagnosis is often delayed and requires high index of suspicion. We here report a case of Aspergillus endocarditis in solid organ transplant recipient.

Bioprosthetic tricuspid valve dysfunction in patients with transvalvular or epicardial pacing leads.

BACKGROUND: Dysfunction of native tricuspid valves due to transvenous pacing leads is well described. Patients with bioprosthetic tricuspid valve (BTV) who need ventricular pacing are often advised epicardial lead placement to avoid potential damage to the BTV although there are no data to support this. OBJECTIVE: The aim of the study was to assess the frequency of BTV dysfunction in patients with permanent transvenous right ventricular pacemaker lead and compare it to patients with epicardial leads. METHODS: A retrospective review of patients with BTV with ventricular pacing lead was conducted. Demographics, lead, BTV, and echocardiographic data were collected. Frequency of BTV dysfunction (moderate or severe) regurgitation or stenosis was compared between epicardial and transvalvular lead groups. RESULTS: Forty-six patients with BTV and ventricular pacing lead (20 transvalvular and 26 epicardial leads) were identified. Mean age was 46 years with the majority being female (85%) and with rheumatic heart disease (87%). Both groups were similar in age, sex, and indications for BTV. Mean echocardiographic follow-up was for 5.5 years (±4.1 years). BTV dysfunction was similar between the transvalvular group with six (30%) patients and the epicardial group with five (19.2%) patients. The incidence of BTV dysfunction was greater in patients in sinus rhythm compared to patients in atrial fibrillation (50% vs 10%, P  =  0.004). CONCLUSION: Development of BTV dysfunction is similar in patients with transvalvular ventricular leads and epicardial leads. The incidence of BTV dysfunction was higher in patients with sinus rhythm compared to atrial fibrillation.

Comparison of echocardiographic parameters in Fabry cardiomyopathy and light-chain cardiac amyloidosis.

BACKGROUND: Fabry cardiomyopathy (FC) and light-chain amyloid cardiomyopathy (AL) present with concentric left ventricular (LV) hypertrophy/remodeling and diastolic rather than systolic dysfunction. Direct comparisons are difficult due to rarity and confounded by variability of LV thickness. AIMS: To compare LV diastolic and systolic properties between patients with FC and AL in a cohort matched for interventricular septal thickness (IVS). METHODS: A two-center echocardiographic analysis was performed, comprising 118 patients with IVS ≥12 mm (FC and AL 59 patients each) matched by IVS. RESULTS: Fabry cardiomyopathy patients had larger LV end-diastolic diameter (47.7 [44.0-50.9] vs 45.0 [41.5-49.0] mm, P = 0.002), better LV ejection fraction (EF 68.7 [63.4-74.0] vs 63.0 [54.0-70.0]%, P = 0.001) and midwall fractional shortening (midFS 14.8 [13.0-16.1] vs 12.1 [8.9-15.0]%, P = 0.006). LV EF <40% was rare in both (2% vs 7%, P = 0.17). AL patients expressed higher LV diastolic dysfunction grade (III in 26% vs 4%, II in 21% vs 12% and I in 54% vs 84%, P = 0.004), with higher E/e' ratio (13.6 [10.2-18.8] vs 9.8 [7.5-12.3], P < 0.0001). Average E/e' ratio and midFS were significantly associated with NYHA severity in both groups (P < 0.05 for all). CONCLUSIONS: Matched AL patients had worse LV diastolic function than FC, driven by E/e'. Significant LV systolic dysfunction was rare overall. MidFS and E/e' were associated with heart failure severity in both groups.

Atrial function in heart transplant recipients operated with the bicaval technique.

OBJECTIVES: In heart transplantation (HTx) with the bicaval technique the whole right atrium (RA) is donor tissue while the left atrium (LA) consists of both donor and recipient tissue. The aims of the study were to describe atrial function in comparison with healthy controls and to identify determinants of dysfunction. DESIGN: Forty-three patients and 30 controls were retrospectively included. Echocardiography was performed within 24 h of right heart catheterization (RHC) (HTx recipients). RESULTS: The peak longitudinal atrial systolic strain (ɛ) described the atrial reservoir function. The LA and RA reservoir function were reduced versus controls (LA-ɛ 18 ± 8 versus 44 ± 10%; RA-ɛ 22 ± 10 versus 69 ± 17%, p < 0.001). There were moderate relationships between atrial-ɛ and ventricular filling pressure (r = -0.64 for LA-ɛ; r = -0.57 for RA-ɛ). In a multiple regression analysis the LA-ɛ was determined by pulmonary capillary wedge pressure (PCWP) and LA minimum volume index (r = -0.71) while RA-ɛ was dependent on the right ventricular ɛ (r = -0.77). CONCLUSIONS: Atrial reservoir function is markedly reduced in HTx recipients related to elevated PCWP and LA-enlargement in the LA and in the RA impaired longitudinal right ventricular function.

Left ventricular volumes by echocardiography in chronic aortic and mitral regurgitations.

Objectives Cut-off values for left ventricular (LV) dimensions indicating severe valve regurgitation have not been defined. The aim of this study was to establish echocardiographic cut-off values for LV dimensions indicating severe chronic aortic (AR) or mitral (MR) regurgitation. Design The hemodynamic significance was confirmed by documented reduction of end-diastolic volume (EDV) and symptom relief after surgery. Eighty-three patients with moderate or severe regurgitation (AR, n = 41; MR, n = 42) without other cardiac conditions underwent prospectively two-dimensional (2DE), real-time three-dimensional (RT3DE) echocardiography and cardiovascular magnetic resonance (CMR) exams within 4 h. Results The relationship between EDVCMR and EDV2DE and EDVRT3DE were strong (R 0.95 and 0.91). EDV index cut-offs for 2DE/RT3DE >87/104 ml/m(2) identified AR patients with severe regurgitation with a positive likelihood ratio (PLR) of 5.0/5.0. The corresponding in patients with MR EDV index cut-offs were >69/87 ml/m(2) with a PLR of 14.9/5.5. LV linear dimensions could not identify patients with severe regurgitation. Conclusions LV volumes by echocardiography can support the diagnosis of severe chronic regurgitation. Importantly, other causes for LV enlargement have to be considered.

Intermittent Malfunction of a Prosthetic Valve-A Diagnostic Challenge.

Intermittent malfunction of a mechanical valve prosthesis is a rare condition that carries serious clinical implications. It results from the periodic entrapment of a prosthetic disk in either an open or closed position leading to transient intravalvular regurgitation or obstruction to flow. The intermittent nature of the malfunction poses a diagnostic challenge, particularly in the era of digital echocardiography. In this manuscript, we describe the Doppler and two-dimensional echocardiographic findings in a patient with intermittent prosthetic mitral valve malfunction.

Spectral Doppler of the Hepatic Veins in Rate, Rhythm, and Conduction Disorders.

Doppler interrogation of blood flow in the hepatic veins (HVs) provides valuable information regarding a wide spectrum of pathological processes that affect the right heart. Systematic analysis of the direction, velocity, and phasicity of the HV waveforms allows one to distinguish normal from abnormal patterns and provides important diagnostic information. Abnormalities in heart rate, rhythm, and intracardiac conduction are commonly encountered during echocardiographic studies. Sinus bradycardia and tachycardia, bradyarrhythmias and tachyarrhythmias as well as atrioventricular conduction disturbances influence the flow pattern in the HVs and may pose a challenge to the correct interpretation of the HV Doppler. Alterations in HV flow that are induced by the electrical abnormalities may mimic right heart pathology. Awareness of these alterations allows one to avoid misinterpretation of the HV signal, helps diagnose the underlying rhythm or conduction abnormality, and permits assessment of the impact on right heart hemodynamics.

The Echocardiographic "Spike and Dome"--Obstruction It Is But Where?

Spectral Doppler interrogation of the descending thoracic and abdominal aorta provides valuable information regarding cardiac and vascular hemodynamics. An abnormal aortic Doppler profile is encountered in pathological conditions that affect the aorta and its branches, the aortic valve, the left ventricle, and the pericardium. Characteristic findings on Doppler interrogation of the aorta are often noted in individuals with obstructive atherosclerotic disease of the aorto-iliac system including severe stenosis or occlusion of the distal aorta and/or iliac arteries. In this manuscript, we highlight the findings on spectral Doppler that led to the identification of occlusive disease in the distal aorta.

Thrombolytic Therapy as the Management of Mitral Transcatheter Valve-in-Valve Implantation Early Thrombosis.

A 70-year-old male underwent mitral transcatheter valve-in-valve implantation for a failed bioprosthesis implanted 11 years earlier. In the first days following the procedure, he developed thrombosis of the new bioprosthesis with restricted cusp motion. The transmitral mean gradient increased significantly despite effective anticoagulation therapy using unfractionated heparin infusion. Low dose and slow infusion of alteplase resulted in resolution of the thrombus and normalisation of cusp motion. Thereafter long-term anticoagulation using a vitamin K antagonist was instituted and the patient remained asymptomatic.

Spectral Doppler of the hepatic veins in pulmonary hypertension.

Pulsed-wave Doppler interrogation of the hepatic veins (HVs) provides a window to right heart hemodynamics and function. Various pathologies that involve the right heart are manifested on the HV Doppler depending on the location and severity of the involvement and its hemodynamic consequences. Pulmonary hypertension (PHTN), a common finding on echocardiographic studies, imparts changes on the HV Doppler that are important to recognize. In this article, we provide a review of the main abnormalities that are encountered on the HV Doppler in patients with PHTN.

Respiratory hemodynamics in the hepatic veins-normal pattern.

Doppler interrogation of blood flow in the hepatic veins (HVs) is a part of any comprehensive echocardiographic examination. Data derived from the HV Doppler provide a useful tool for the assessment of right heart function. Beyond its dependence on the cardiac cycle, right heart hemodynamics, and compliance of the liver parenchyma, blood flow in the HVs is influenced by the respiratory cycle. Systematic analysis of the behavior of the HV Doppler during respiration allows one to recognize normal and abnormal flow-patterns and distinguish among various disease states that involve the right heart. In this manuscript we discuss the effect of respiration on the HV Doppler in individuals with normal right heart function.

Respiratory hemodynamics in the hepatic veins--abnormal patterns.

The flow pattern in the hepatic veins (HVs) is dependent on the cardiac cycle and right heart hemodynamics and influenced by the respiratory cycle and the liver parenchyma. Most disease states that affect the right heart alter the HV Doppler in a manner independent of the respiratory cycle. Some diseases that typically involve the pericardium, right ventricular myocardium, or respiratory system confer characteristic changes to the HV flow in a manner dependent on the respiratory cycle. Analysis of the HV Doppler with assessment of the respiratory changes in flow and their timing helps to distinguish among the various disease states. In this manuscript, we discuss the effect of respiration on HV flow in patients with abnormal right heart function and illustrate the use of the respiratory changes in the HV Doppler as a tool for diagnosis.

Spectral Doppler of the Hepatic Veins in Noncardiac Diseases: What the Echocardiographer Should Know.

In most instances, the flow profile in the hepatic veins (HVs) reflects the fluctuation of pressure within the right atrium. Thus, interrogation of blood flow in the HVs is highly useful for the evaluation of right heart hemodynamics and has become an integral part of any routine echocardiographic examination. However, flow in the HVs is also affected by the state of the liver parenchyma and by the fluctuation of pressure within the thoracic cavity. Therefore, liver and pulmonary pathologies influence the flow pattern in the HVs and may lead to its dissociation from right heart hemodynamics. Echocardiographers should familiarize themselves with the findings on HV Doppler in noncardiac diseases to avoid misinterpretation and incorrect diagnosis.

Spectral Doppler interrogation of mitral regurgitation -spot diagnosis.

Mitral regurgitation (MR) is one of the most common valvular lesions that are readily identified by transthoracic echocardiography. Color Doppler imaging is the modality of choice for the recognition of MR, and it plays an important role in the assessment of regurgitation severity. Continuous wave (CW) Doppler is commonly used to interrogate the MR signal, and this modality can provide highly useful data regarding several physiological and pathological parameters. In this manuscript, we present a series of cases that illustrate the various hemodynamic parameters that can be derived from analysis of the CW Doppler signal of MR.

Spectral Doppler interrogation of the pulmonary veins in atrial septal defect.

The various components of the pulmonary venous (PV) flow are linked to physiological and pathological changes that predominantly occur in the left heart. Thus, spectral Doppler interrogation of the PVs provides hemodynamic insight mainly into left-sided cardiac function. An exception to the dependence of PV flow on left heart events occurs in the setting of an atrial septal defect (ASD). The latter causes a portion of the PV blood flow, intended to cross the mitral valve, to be channeled into the more compliant right heart. This phenomenon makes the PV flow more dependent on the left-to-right interatrial shunt. The identification on the PV Doppler of a pattern that suggests uncoupling with left heart hemodynamics should raise the suspicion of an underlying ASD.

The various hemodynamic profiles of the patent ductus arteriosus in adults.

The patent ductus arteriosus (PDA) has diverse clinical and hemodynamic manifestations depending on its size and the degree of the ensuing left-to-right shunt. A small PDA that causes minor shunting has no major hemodynamic consequences. Conversely, a large PDA with a significant left-to-right shunt may lead to various hemodynamic abnormalities. These include left-sided volume overload that may result in heart failure and/or pulmonary hypertension, the latter being a flow-dependent and mostly reversible phenomenon. The most feared complication is the development of severe and irreversible pulmonary hypertension (Eisenmenger physiology). In this manuscript, we provide examples of the various hemodynamic profiles of PDA as assessed by echocardiography in the adult population.

Spectral Doppler interrogation of the patent foramen ovale-a window to left heart hemodynamics.

Spectral Doppler interrogation of flow across a patent foramen ovale (PFO) allows recording of the instantaneous pressure gradient between left and right atrium (RA). The assessment of RA pressure using the size and collapsibility of the inferior vena cava would thus allow estimation of left atrial (LA) pressure. In this article, we illustrate the value of spectral Doppler interrogation of flow across the PFO by transthoracic echocardiography as a novel and simple tool for the assessment of LA pressure and left cardiac hemodynamics in addition to the conventional noninvasive parameters.