Natural history and outcome of light chain deposition disease.

Light chain deposition disease (LCDD) is characterized by the deposition of monotypic immunoglobulin light chains in the kidney, resulting in renal dysfunction. Fifty-three patients with biopsy-proven LCDD were prospectively followed at the UK National Amyloidosis Center. Median age at diagnosis was 56 years, and patients were followed for a median of 6.2 years (range, 1.1-14.0 years). Median renal survival from diagnosis by Kaplan-Meier analysis was 5.4 years, and median estimated patient survival was 14.0 years; 64% of patients were alive at censor. Sixty-two percent of patients required dialysis, and median survival from commencement of dialysis was 5.2 years. There was a strong association between hematologic response to chemotherapy and renal outcome, with a mean improvement in glomerular filtration rate (GFR) of 6.1 mL/min/year among those achieving a complete or very good partial hematologic response (VGPR) with chemotherapy, most of whom remained dialysis independent, compared with a mean GFR loss of 6.5 mL/min/year among those achieving only a partial or no hematologic response (P < .009), most of whom developed end-stage renal disease (ESRD; P = .005). Seven patients received a renal transplant, and among those whose underlying clonal disorder was in sustained remission, there was no recurrence of LCDD up to 9.7 years later. This study highlights the need to diagnose and treat LCDD early and to target at least a hematologic VGPR with chemotherapy, even among patients with advanced renal dysfunction, to delay progression to ESRD and prevent recurrence of LCDD in the renal allografts of those who subsequently receive a kidney transplant.

Prognostic Value of Late Gadolinium Enhancement Cardiovascular Magnetic Resonance in Cardiac Amyloidosis.

BACKGROUND: The prognosis and treatment of the 2 main types of cardiac amyloidosis, immunoglobulin light chain (AL) and transthyretin (ATTR) amyloidosis, are substantially influenced by cardiac involvement. Cardiovascular magnetic resonance with late gadolinium enhancement (LGE) is a reference standard for the diagnosis of cardiac amyloidosis, but its potential for stratifying risk is unknown. METHODS AND RESULTS: Two hundred fifty prospectively recruited subjects, 122 patients with ATTR amyloid, 9 asymptomatic mutation carriers, and 119 patients with AL amyloidosis, underwent LGE cardiovascular magnetic resonance. Subjects were followed up for a mean of 24±13 months. LGE was performed with phase-sensitive inversion recovery (PSIR) and without (magnitude only). These were compared with extracellular volume measured with T1 mapping. PSIR was superior to magnitude-only inversion recovery LGE because PSIR always nulled the tissue (blood or myocardium) with the longest T1 (least gadolinium). LGE was classified into 3 patterns: none, subendocardial, and transmural, which were associated with increasing amyloid burden as defined by extracellular volume (P<0.0001), with transitions from none to subendocardial LGE at an extracellular volume of 0.40 to 0.43 (AL) and 0.39 to 0.40 (ATTR) and to transmural at 0.48 to 0.55 (AL) and 0.47 to 0.59 (ATTR). Sixty-seven patients (27%) died. Transmural LGE predicted death (hazard ratio, 5.4; 95% confidence interval, 2.1-13.7; P<0.0001) and remained independent after adjustment for N-terminal pro-brain natriuretic peptide, ejection fraction, stroke volume index, E/E', and left ventricular mass index (hazard ratio, 4.1; 95% confidence interval, 1.3-13.1; P<0.05). CONCLUSIONS: There is a continuum of cardiac involvement in systemic AL and ATTR amyloidosis. Transmural LGE is determined reliably by PSIR and represents advanced cardiac amyloidosis. The PSIR technique provides incremental information on outcome even after adjustment for known prognostic factors.

A study of implanted cardiac rhythm recorders in advanced cardiac AL amyloidosis.

AIMS: AL amyloidosis may respond to chemotherapy but two-thirds of patients with severe cardiac involvement die within a year of diagnosis, purportedly from tachyarrhythmias or electromechanical dissociation. We sought to characterize the nature of cardiac arrhythmias in severe cardiac AL amyloidosis using implanted cardiac rhythm recorders. METHODS AND RESULTS: Implantable loop recorders (ILRs) were inserted within 24 h of baseline evaluation at the UK National Amyloidosis Centre, into 20 consecutive patients with newly diagnosed severe cardiac AL amyloidosis and symptoms of syncope or pre-syncope. Weekly ILR recordings and additional recordings at the time of symptoms were obtained. Median (range) follow-up from baseline was 308 (10-399) days. Thirteen patients died, and median survival in the whole cohort was 61 days from device insertion. In each of eight evaluable cases, death was heralded by bradycardia, usually associated with complete atrioventricular block (CAVB), followed shortly thereafter by pulseless electrical activity. Four patients received pacemakers, a median (range) of 7 (3-38) h after development of symptomatic CAVB, but these did not prevent rapid cardiac decompensation and death in three cases. Despite 272 loop recordings, there was only one episode of non-sustained ventricular tachycardia, which was preceded by severe bradycardia. Patients who died had significantly worse global left ventricular strain on echocardiography (P = 0.029) and reduced 6 min walk distance (P = 0.048) at baseline compared with survivors. CONCLUSIONS: The discovery that bradyarrhythmias heralded terminal cardiac decompensation in most patients with severe cardiac AL amyloidosis supports a study of prophylactic pacemaker insertion in this patient population.

Management of mitral stenosis: a systematic review of clinical practice guidelines and recommendations.

A number of guidelines exist with recommendations for diagnosis and management of mitral stenosis (MS). We systematically reviewed existing guidelines for diagnosis and management of MS, highlighting their similarities and differences, in order to guide clinical decision-making. We searched national and international guidelines in MEDLINE and EMBASE (5/4/2011-5/9/2021), the Guidelines International Network, Guideline Library, National Guideline Clearinghouse, National Library for Health Guidelines Finder, Canadian Medical Association Clinical Practice Guidelines Infobase, and websites of relevant organizations. Two independent reviewers screened titles and abstracts, and the full text of potentially relevant articles where needed. Selected guidelines were assessed for rigor of development; only guidelines with Appraisal of Guidelines for Research and Evaluation II instrument score >50% were included in the final analysis. Four guidelines were retained for analysis. There was consensus for percutaneous mitral balloon commissurotomy as first-line treatment of symptomatic severe rheumatic MS with suitable anatomy. In patients with unfavourable anatomy, surgical intervention should be considered. Exercise testing is indicated if discrepancy exists between symptoms and echocardiographic measurements. There was no clear divide between rheumatic MS and degenerative MS for their respective diagnoses and management. Pregnancy in severe MS is discouraged and the stenosis should be treated before conception. Long-term antibiotic prophylaxis is recommended for patients with rheumatic MS. Recommendations for the management of patients with mixed valvular diseases are lacking.

A rare finding of giant accessory mitral valve tissue: a case report.

BACKGROUND: Accessory mitral valve tissue (AMVT) is a rare anomaly that can be detected in the first decade. It is associated with other congenital cardiac abnormalities, such as ventricular septal defect. When detected in adulthood, it is usually an incidental finding on echocardiography. Symptomatic individuals can present with breathlessness, syncope, and features of distal tissue embolization. Cardiac surgery is indicated in those with significant left ventricular outflow tract obstruction. CASE SUMMARY: A 45-year-old man without any significant medical history was referred due to an abnormal electrocardiogram. He was asymptomatic from a cardiac perspective. Echocardiography revealed the presence of a giant mobile mass attached to the anterior mitral valve leaflet and prolapsing into the left ventricular outflow tract (LVOT). This was classified as Type IIB2 AMVT. As there was no dynamic outflow tract obstruction on subsequent treadmill stress echocardiography, and in the absence of other coexistent congenital abnormality, surgical excision was not performed. DISCUSSION: It is important to exclude significant obstruction when a large AMVT is seen to be prolapsing into the LVOT. Three-dimensional echocardiography is the tool of choice for anatomical classification and to assess for concomitant congenital cardiac abnormalities.

Impact on survival of combination inhalers in patients with COPD at high risk of cardiovascular events.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) and cardiovascular disease often co-exist and are both leading causes of death worldwide. Published data have previously suggested trends toward improved survival for patients taking long-acting ß agonists combined with inhaled corticosteroids (LABA-ICS) through beneficial actions on the respiratory and cardiovascular systems. We sought to explore this in a real-world setting. METHODS: A population-based longitudinal propensity score-matched cohort study was conducted in the United Kingdom, 1998-2015. Patients were identified from the Clinical Practice Research Datalink (CPRD) which is linked to Hospital Episode Statistics (HES) and Office for National Statistics (ONS) mortality records. All patients had a validated diagnosis of COPD and were at high risk for cardiovascular events (history of myocardial infarction, diabetes mellitus, ischaemic heart disease, stroke and peripheral arterial disease). The primary outcome was all-cause mortality. RESULTS: The treatment group was composed of 2687 new users of LABA-ICS with COPD and comparisons were made in a control population of 2687 COPD patients prescribed LABAs alone. At three years follow-up death occurred in 358 (13.3%) patients in the treatment group and 427 (15.9%) patients in the control group. The use of LABA-ICS was modestly associated with improved survival compared to use of LABAs (hazard ratio 0.82, 95% CI 0.71-0.95, P = 0.007). CONCLUSIONS: Among patients with COPD with either established cardiovascular disease or at high risk of an index cardiovascular event, LABA-ICS inhaled therapy, compared with LABAs alone, was associated with a significantly improved survival.

The evolving landscape of oral anti-arrhythmic prescriptions for atrial fibrillation in England: 1998-2014.

AIMS: An important decision in the management of patients with atrial fibrillation is whether to adopt a rate or rhythm control strategy. Options for the latter include oral membrane-active anti-arrhythmic drugs (AADs) or catheter ablation. Recent prescription trends may have been affected by the introduction of dronedarone and an increasing number of reports suggesting increased mortality in those taking AADs. We describe the trend in oral AAD prescriptions in England in the period 1998-2014. METHODS AND RESULTS: We conducted a retrospective study using data from the Prescription Cost Analysis system, which holds information on every prescription dispensed in the community in England. We obtained data from 1998 to October 2014 for all Class Ia, Ic, and III AADs. Amiodarone and sotalol remain the most commonly prescribed AADs in England, though the use of both is decreasing. There has been a linear increase in the uptake of flecainide. Dronedarone prescriptions peaked in 2011, and our most recent data show that amiodarone prescriptions are 25-fold those of dronedarone. CONCLUSION: There is a decline in the use of amiodarone and sotalol consistent with the growing safety concerns with these drugs along with neutral results from landmark trials comparing rate and rhythm control. Dronedarone has failed to make an impact on AAD prescribing. In contrast, flecainide has seen an increase in use during the study period.

Renal denervation for the management of resistant hypertension.

Renal sympathetic denervation (RSD) as a therapy for patients with resistant hypertension has attracted great interest. The majority of studies in this field have demonstrated impressive reductions in blood pressure (BP). However, these trials were not randomized or sham-controlled and hence, the findings may have been overinflated due to trial biases. SYMPLICITY HTN-3 was the first randomized controlled trial to use a blinded sham-control and ambulatory BP monitoring. A surprise to many was that this study was neutral. Possible reasons for this neutrality include the fact that RSD may not be effective at lowering BP in man, RSD was not performed adequately due to limited operator experience, patients' adherence with their anti-hypertensive drugs may have changed during the trial period, and perhaps the intervention only works in certain subgroups that are yet to be identified. Future studies seeking to demonstrate efficacy of RSD should be designed as randomized blinded sham-controlled trials. The efficacy of RSD is in doubt, but many feel that its safety has been established through the thousands of patients in whom the procedure has been performed. Over 90% of these data, however, are for the Symplicity™ system and rarely extend beyond 12 months of follow-up. Long-term safety cannot be assumed with RSD and nor should it be assumed that if one catheter system is safe then all are. We hope that in the near future, with the benefit of well-designed clinical trials, the role of renal denervation in the management of hypertension will be established.

Natural history and outcomes in localised immunoglobulin light-chain amyloidosis: a long-term observational study.

BACKGROUND: Localised immunoglobulin light-chain amyloidosis, involving one type of tissue, is rare. Little systematic data exists regarding clinical presentations, course or outcomes, or risk of progression to systemic amyloidosis. We aimed to report clinical features and outcomes of a large series of patients with localised light-chain amyloidosis. METHODS: We examined data for all patients with localised amyloidosis who were diagnosed, assessed, and followed at the UK National Amyloidosis Centre (NAC) between Jan 2, 1980, and Dec 15, 2011, from the NAC database and written records. The inclusion criteria was the presence of biopsy sample proven localised amyloidosis classified as biopsy proven amyloid deposition confined to one site or tissue proven by histology of the tissue examined), without any evidence of vital organ involvement, which was defined as cardiac, renal, or liver involvement or peripheral or autonomic neuropathy and treatment naive. FINDINGS: We identified 606 patients with biopsy proven localised amyloidosis (likely light-chain type in 98%) from 5050 newly diagnosed patients with all types of amyloidosis. Median age was 59·5 years (IQR 50·2-74·5). The most common sites included bladder (95; 16%), laryngeal or tonsillar (92; 15%), cutaneous (84; 14%), and pulmonary nodular (47; 8%). 121 (20%) had a monoclonal immunoglobulin or abnormal circulating free light chains. At median follow-up of 74·4 months (IQR 37·2-132·0), seven (1%) patients progressed to systemic immunoglobin light-chain amyloidosis. 270 (51%) patients had one repeated treatment intervention and 112 (21%) had more than one repeated treatment interventions (predominantly localised debulking). The estimated 5-year overall survival was 90·6% (95% CI 87·7-92·9) and 10-year overall survival was 80·3% (75·1-84·1). In patients aged 70 years or older, median overall survival was 12·1 years (95% CI 10·5-13·7). INTERPRETATION: Localised immunoglobulin light-chain amyloidosis has an excellent prognosis with no apparent effect on life expectancy. Evolution into systemic immunoglobulin light chain amyloidosis is very rare. FUNDING: None.

Life-saving implantable cardioverter defibrillator therapy in cardiac AL amyloidosis.

Cardiac involvement is the main determinant of prognosis in systemic monoclonal immunoglobulin light chain (AL) amyloidosis. Ventricular arrhythmias and sudden cardiac death are not uncommon. The electrical events that precede sudden death, and their potential to be treated effectively, remain undefined. There are no European guidelines for the use of implantable cardioverter defibrillator (ICD) in amyloidosis. ICDs in general are not usually offered to patients with a life expectancy of less than 1 year. We describe a patient who presented with cardiac AL amyloidosis who underwent prophylactic ICD implantation for the prevention of sudden cardiac death during treatment with chemotherapy, in whom life-threatening ventricular arrhythmia was successfully terminated over a 3-year period.

Coronary artery ectasia as a culprit for acute myocardial infarction: review of pathophysiology and management.

Coronary artery ectasia (CAE) is defined as localized coronary dilatation, which exceeds the diameter of normal adjacent segments or the diameter of the patient's largest coronary vessel by 1.5 times. The pathophysiology of CAE remains unclear as its relationship with atherosclerosis remains only modestly established. The histological variances and conflicting reports of the role of traditional cardiovascular risk factors, also, weakens the significance of such association. The slow coronary flow (CSF) of CAE may lead to ischemic and thrombotic events, a mechanism that has never been fully elucidated, but may play a fundamental role in its pathogenesis. While pure, non-atherosclerotic, CAE is believed to have better prognosis when compared to atherosclerotic obstructive CAE, it is thought that CAE is not a simple condition but rather has an adverse clinical course. Nevertheless, long-term prognosis and outcome of CAE is similar to atherosclerotic-non-CAE. Since CAE was first described, oral anticoagulants have been considered as a valid treatment option. Dual antiplatelet therapy is widely employed in acute coronary syndrome (ACS), which also applies to CAE patients presenting with ACS. However, there is a significant uncertainty about the best treatment strategy for CAE in acute myocardial infarction. We hereby report a variety of presentations of CAE complicated with ST elevation myocardial infarction (STEMI). Pathophysiological and anatomical varieties of ectatic coronary culprit lesions represent clinical challenges in uniformly managing this condition. Our review is unique in critically showing the pathophysiology, available controversial evidence upon management and prognostic features of CAE with STEMI.