Naser, Jwan A

Abstract Aims Atrial functional mitral regurgitation (AFMR) has been associated with atrial fibrillation (AF) and heart failure with preserved ejection fraction. However, data on incident AFMR are scarce. We aimed to study the incidence, risk factors, and clinical significance of AFMR in AF or sinus rhythm (SR). Methods and results Adults with new diagnosis of AF and adults in SR were identified. Patients with >mild MR at baseline, primary mitral disease, cardiomyopathy, left-sided valve disease, previous cardiac surgery, or with no follow-up echocardiogram were excluded. Diastolic dysfunction (DD) was indicated by ≥2/4 abnormal diastolic function parameters [mitral medial e′, mitral medial E/e′, tricuspid regurgitation velocity, left atrial volume index (LAVI)]. Overall, 1747 patients with AF and 29 623 in SR were included. Incidence rate of >mild AFMR was 2.6 per 100 person-year in new-onset AF and 0.7 per 100 person-year in SR, P < 0.001. AF remained associated with AFMR in a propensity score-matched analysis based on age, sex, and comorbidities between AF and SR [hazard ratio: 3.80 (95% confidence interval 3.04–4.76)]. Independent risk factors associated with incident AFMR were age ≥65 years, female sex, LAVI, and DD in both AF and SR, in addition to rate (vs. rhythm) control in AF. Incident AFMR was independently associated with all-cause death in both groups (both P < 0.001). Conclusions AF conferred a three-fold increase in the risk of incident AFMR. DD, older age, left atrial size, and female sex were independent risk factors in both SR and AF, while rhythm control was protective. AFMR was universally associated with worse mortality.

Abstract Background Caseous calcification of the mitral annulus is an extremely rare variant of mitral annulus calcification occurring in <1% of cases. The degeneration of caseous masses could act as a source of embolic strokes and a nidus for infective endocarditis (IE). Case summary A man in his sixties presented with transient left arm weakness. His history was pertinent for bioprosthetic aortic valve replacement secondary to endocarditis and recent pneumococcal pneumonia complicated by empyema and bacteraemia. He was still on intravenous antibiotics when he presented. Evaluation including magnetic resonance imaging of the brain, transoesophageal echocardiography, and computed tomography (CT) of the chest revealed multifocal embolic strokes, degenerative bioprosthetic aortic valve dysfunction, mitral annular calcification with mobile calcific masses, and persistent empyema. 18F-fluorodeoxyglucose–positron emission tomography–CT showed indeterminate activity across a portion of the posterior mitral leaflet and no activity on the bioprosthetic aortic valve. The patient was deemed high risk for surgery and was treated with 6-week course of antibiotics both for the empyema and the possible IE of the native mitral valve. Repeat echocardiography 40 days later showed stable mitral masses. At 4 months of follow up, the patient had no evidence of recurrent clinical strokes. Discussion Caseous calcification of the mitral annulus is a rare but an increasingly recognized predisposing factor for embolic strokes and IE. Treatment ideally involves surgical resection of the calcified masses in such cases.

Objective Graves’ disease (GD) can both aggravate pre-existing cardiac disease and cause de novo heart failure (HF), but large-scale studies are lacking. We aimed to investigate the incidence, risk factors and outcomes of incident GD-related HF. Methods Patients with GD (2009–2019) were retrospectively included. HF with reduced ejection fraction (HFrEF) was defined by left ventricular ejection fraction <50% and Framingham criteria, while HF with preserved ejection fraction (HFpEF) was defined according to the HFA-PEFF criteria. HF due to ischaemia, valve disorder or other structural heart disease was excluded. Proportional hazards regression was used to analyse risk factors and outcomes. Results Of 1371 patients with GD, HF occurred in 74 (5.4%) patients (31 (2.3%) HFrEF; 43 (3.1%) HFpEF). In HFrEF, atrial fibrillation (AF) (HR 10.5 (3.0–37.3), p<0.001) and thyrotropin receptor antibody (TRAb) level (HR 1.05 (1.01–1.09) per unit, p=0.007) were independent risk factors. In HFpEF, the independent risk factors were chronic obstructive pulmonary disease (HR 7.2 (3.5–14.6), p<0.001), older age (HR 1.5 (1.2–2.0) per 10 years, p=0.001), overt hyperthyroidism (HR 6.4 (1.5–27.1), p=0.01), higher body mass index (BMI) (HR 1.07 (1.03–1.10) per unit, p=0.001) and hypertension (HR 3.1 (1.3–7.2), p=0.008). The risk of cardiovascular hospitalisations was higher in both HFrEF (HR 10.3 (5.5–19.4), p<0.001) and HFpEF (HR 6.7 (3.7–12.2), p<0.001). However, only HFrEF was associated with an increased risk of all-cause mortality (HR 5.17 (1.3–19.9), p=0.02) and ventricular tachycardia/fibrillation (HR 64.3 (15.9–259.7), p<0.001). Conclusion De novo HF occurs in 5.4% of patients with GD and is associated with increased risk of cardiovascular hospitalisations and mortality. Risk factors include AF, higher TRAb, higher BMI and overt hyperthyroidism.

Objective Bioprosthetic valve thrombosis (BPVT) is increasingly recognised as a major cause of prosthetic dysfunction in the first years postimplantation. How early abnormal gradients can be detected prior to diagnosis and how fast they normalise with anticoagulant therapy is unknown. We set forth to (1) evaluate patterns of increase in gradients prior to BPVT diagnosis and (2) characterise time-course of response to anticoagulation. Methods Patients treated with warfarin for BPVT (1999–2019) with clinically significant reduction of mean gradients (≥25%) were identified retrospectively. Recovery was defined as gradient decrease ≥50%, to postimplantation or to normal-range gradients per position, model and size. Time-to-BPVT (implantation—BPVT diagnosis), potential diagnostic delay (first abnormal gradient by position, model and size—BPVT diagnosis) and time-to-recovery (BPVT diagnosis—complete resolution) were recorded. Results 77 patients were identified; 32 (42%) aortic (23 surgical—12 porcine, 11 pericardial; 9 transcatheter); 24 (31%) mitral; 21 (27%) tricuspid. Median time-to-BPVT was 24, 21 and 10 months, respectively. Potential diagnostic delay was median 21 months for aortic, 4 months for mitral, but 0 for tricuspid. Recovery was significantly faster in mitral than aortic (median 2.5 vs 4.8 months, p=0.038) and tricuspid (median 5.9 months, p=0.025) positions. Porcine aortic valves responded faster than pericardial aortic valves (median 2.9 vs 20.3 months, p=0.004). Conclusion Gradients start to increase months before the clinical BPVT diagnosis. Recovery is faster in mitral and surgical aortic porcine valves; a longer warfarin trial seems indicated in tricuspid and surgical aortic pericardial valves.

Abstract Background Bioprosthetic tricuspid valve stenosis (TS) is an uncommon and frequently under-diagnosed condition. Although the resulting right heart failure symptoms are well-known, the associated thrombogenic potential is under-recognized. Case summary A 44-year-old woman with bioprosthetic tricuspid valve (TV) replacement in 2001 was referred for urgent consultation due to acute worsening of dyspnoea and severe swelling and pain in her left arm and neck. She was diagnosed with atrial fibrillation 6 months before the presentation and was found to have right atrial (RA) thrombus with pulmonary embolism and extensive retrograde venous extension 1 month prior. Review of studies done at her local institution revealed 10 mmHg mean gradient (MG) across the bioprosthetic TV that was only reported as mild–moderate TS. Echocardiography done at our instruction confirmed suspicion of severe TS with calcified immobile leaflets. Computed tomography showed persistent RA thrombus and therefore surgical replacement of the TV was undertaken. Subsequently, patient’s dyspnoea rapidly improved. Discussion Progressive dyspnoea and symptoms of right heart failure in a patient with a history of bioprosthetic TV replacement should be investigated for prosthetic valve dysfunction. Due to its rarity, TS diagnosis can be overlooked on routine echocardiography. In our patient, despite a measured MG of 10 mmHg, the presence of critical TS was not initially recognized. As TS is associated with increased thrombogenic potential and given the rare occurrence of in situ RA thrombosis, physicians must have a high index of suspicion for TS in the appropriate clinical context.

Abstract Aims Beat-to-beat variability in cycle length is well-known in atrial fibrillation (Afib); whether this also translates to variability in annulus size remains unknown. Defining annulus maximal size in Afib is critical for accurate selection of percutaneous devices given the frequent association with mitral and tricuspid valve diseases. Methods and results Images were obtained from 170 patients undergoing 3D echocardiography [100 (50 sinus rhythm (SR) and 50 Afib) for mitral annulus (MA) and 70 (35 SR and 35 Afib) for tricuspid annulus (TA)]. Images were analysed for differences in annular dynamics with a commercially available software. Number of cardiac cycles analysed was 567 in mitral valve and 346 in tricuspid valve. Median absolute difference in maximal MA area over four to six cycles was 1.8 cm2 (range 0.5–5.2 cm2) in Afib vs. 0.8 cm2 (range 0.1–2.9 cm2) in SR, P &lt; 0.001. Maximal MA area was observed within 30–70% of the R-R interval in 81% of cardiac cycles in SR and in 73% of cycles in Afib. Median absolute difference in maximal TA area over four to six cycles was 1.4 cm2 (range 0.5–3.6 cm2) in Afib vs. 0.7 cm2 (range 0.3–1.7 cm2) in SR, P &lt; 0.001. Maximal TA area was observed within 60–100% of the R-R interval in 81% of cardiac cycles in SR, but only in 49% of cycles in Afib. Conclusion MA and TA reach maximal size within a broad time interval centred around end-systole and end-diastole, respectively, with significant beat-to-beat variability. Afib leads to a larger beat-to-beat variability in both timing of occurrence and values of annulus size than in SR.

INTRODUCTION: Duodenal adenocarcinoma is rare and often has a vague clinical presentation. Therefore most patients have advanced disease (stage III or IV) at the time of diagnosis, which heralds poor prognosis. Membranous nephropathy can be associated with solid tumors; however duodenal adenocarcinoma presenting as membranous nephropathy has not been reported in the literature. CASE DESCRIPTION/METHODS: A 78-year-old male presented with worsening dyspnea, nausea and anorexia over a period of several months. Further workup revealed proteinuria secondary to biopsy-proven membranous nephropathy. PLA2R antibodies were negative, which initiated an evaluation for secondary membranous nephropathy. Physical examination revealed anasarca. His creatinine was 3.4 mg/dL, and extensive workup for a secondary cause of membranous nephropathy, including ANA, C3, C4, and hepatitis B and C testing was negative. CT of the abdomen showed upper abdominal and mesenteric adenopathy. His presentation was complicated by gastrointestinal bleeding with a hemoglobin of 5.3 g/dL. Esophagogastroduodenoscopy revealed a large villous, infiltrative sessile mass in the third portion of the duodenum [Figure 1]. Biopsies showed moderately differentiated adenocarcinoma. Endosonographic ultrasound showed malignant-appearing lymph nodes and fine needle aspiration of the largest celiac lymph node confirmed metastatic adenocarcinoma. Therefore surgical resection was not recommended. The patient was started on 5-fluorouracil and oxaliplatin. Membranous nephropathy was due to a paraneoplastic syndrome and its resolution was dependent on the course of the duodenal adenocarcinoma. Unfortunately, his course was complicated by worsening renal failure and he required intensive care with continuous renal replacement therapy and non-invasive ventilation for respiratory failure. He recovered slowly and was discharged home on hemodialysis. Follow up imaging periodically over the following year revealed peritoneal, lung and liver metastasis. The patient eventually pursued palliative care and he passed away. DISCUSSION: The unusual presentation of duodenal adenocarcinoma in the form of membranous nephropathy led to a delayed diagnosis with poor candidacy for surgical resection. Age- and risk-appropriate assessment for malignancy is recommended in secondary membranous nephropathy without a clear etiology. Gastrointestinal malignancy should be in the differential especially when anemia is present.