Prognostication and Interventional Guidance Using Acceleration-Ejection Time Ratio in Undifferentiated Paradoxical Low-Flow Low-Gradient Aortic Stenosis.

BACKGROUND: Studies in paradoxical low-flow low-gradient aortic stenosis (PLFAS) have demonstrated conflicting outcomes with variable survival advantage from aortic valve replacement (AVR). PLFAS is a heterogeneous composition of patients with uncertainty regarding true stenosis severity that continues to confound decision-making for AVR. OBJECTIVES: The purpose of this study was to investigate the utility of the Doppler acceleration (AT) to ejection (ET) time ratio (AT:ET) for prediction of prognosis and benefit from AVR in undifferentiated PLFAS. METHODS: Patients with echocardiographic findings of PLFAS (aortic valve area <1.0 cm2 or indexed aortic valve area <0.6 cm2/m2, mean gradient <40 mm Hg, indexed stroke volume <35 mL/m2, and left ventricular ejection fraction ≥50%) were identified and grouped according to an AT:ET cutoff of 0.35. The primary outcome was a 5-year composite of cardiac mortality or AVR. Secondary outcomes included the individual components of the primary endpoint and all-cause mortality at 5 years. Effect of AVR was analyzed in the AT:ET <0.35 and ≥0.35 groups. RESULTS: A total of 171 PLFAS patients (median age 77.0 years, 57% women) were followed for a median of 8.9 years. AT:ET ≥0.35 was an independent predictor of the primary outcome (HR: 4.77 [95% CI: 2.94-7.75]; P < 0.001) with incremental value over standard indices of stenosis severity (net reclassification improvement: 0.57 [95% CI: 0.14-0.84]). AT:ET ≥0.35 also remained predictive of increased cardiac death (HR: 2.91 [95% CI: 1.47-5.76]; P = 0.002) and AVR (HR: 8.45 [95% CI: 4.16-17.1]; P < 0.001), respectively, following competing risk analysis. No difference in all-cause mortality was observed. AVR in the AT:ET ≥0.35 group was associated with significant reductions in 5-year cardiac (HR: 0.09 [95% CI: 0.02-0.36]; P < 0.001) and all-cause mortality (HR: 0.16 [95% CI: 0.07-0.38]; P < 0.001). No improvement in survival from AVR was demonstrated in AT:ET <0.35 patients. CONCLUSIONS: AT:ET ≥0.35 in PLFAS predicts poorer outcomes and/or need for AVR. In undifferentiated PLFAS patients, AT:ET may have a potential role in improving patient selection for prognostic AVR.

Echocardiography Versus Magnetic Resonance Imaging Quantification and Novel Algorithm for Isolated Severe Tricuspid Regurgitation.

Transthoracic echocardiography (TTE) is the first-line tool to evaluate isolated tricuspid regurgitation (TR) but it has limitations and its TR quantification compared with magnetic resonance imaging (MRI) has been studied infrequently. We compared isolated severe TR quantification by TTE against MRI and developed a novel TTE-based algorithm. Isolated TR patients graded severe by TTE and who underwent MRI January 2007 to June 2019 were studied. The TTE and MRI measurements were analyzed by correlation, area under receiver-operative characteristics curve (AUC), and classification and regression tree algorithm of TTE parameters to best identify MRI-derived severe TR (regurgitant volume ≥45 ml and/or fraction ≥50%). A total of 108 of 262 (41%) that were graded as severe TR by TTE also had severe TR by MRI. There were moderate correlations between TTE and MRI in the quantification of TR severity and right atrial size (Pearson r = 0.428 to 0.645) but none to modest correlations between them in right ventricle quantification. The key TTE parameters to identify MRI-derived severe TR in the decision tree regression algorithm were right atrial volume indexed ≥47 ml/m2 and effective regurgitant orifice area ≥0.45 cm2 and especially if there is right ventricle free wall strain ≥ -9.5%. This novel algorithm has an AUC of 0.76% and 79% agreement to detect severe TR by MRI, which higher than the American Society of Echocardiography criteria with AUC 0.68% and 66% agreement (p = 0.006 and p <0.001, respectively). In conclusion, TTE-derived TR and right atrial quantification had moderate correlation and discrimination of severe TR by MRI, from which a novel TTE algorithm was derived, which had incrementally a higher accuracy than contemporary guidelines' criteria alone.

Novel Multi-Parametric Mitral Annular Calcification Score Predicts Outcomes in Mitral Valve Dysfunction.

The objective of the study was to construct a multi-parametric mitral annular calcification (MAC) score using computed tomography (CT) features for prediction of outcomes in patients undergoing mitral valve surgery. We constructed a multi-parametric MAC score, which ranges between 2 and 12, and consists of Agatston calcium score (1 point: <1000 Agatston units (AU); 2 points: 1000-<3000 AU; 3 points: 3000-5000 AU; 4 points: >5000 AU), quantitative MAC circumferential angle (1 point: <90°; 2 points: 90-<180°; 3 points: 180-<270°; 4 points: 270-360°), involvement of trigones (1 point: 1 trigone; 2 points: both trigones), and 1 point each for myocardial infiltration and left ventricular outflow tract extension/involvement of aorto-mitral curtain. The association between MAC score and clinical outcomes was evaluated. The study cohort consisted of 334 patients undergoing mitral valve surgery (128 mitral valve repairs, 206 mitral valve replacements) between January 2011 and September 2019, who had both non-contrast gated CT scan and evidence of MAC. The mean age was 72 ± 11 years, with 58% of subjects being female. MAC score was a statistically significant predictor of total operation time (P<0.001), cross-clamp time (P = 0.001) and in-hospital complications (P = 0.003). Additionally, MAC score was a significant predictor of time to all-cause death (P = 0.046). A novel multi-parametric score based on CT features allowed systematic assessment of MAC, and predicted clinical outcomes in patients with mitral valve dysfunction undergoing mitral valve surgery.

A retrospective analysis of the investigative practices of acute limb ischaemia presenting with an unknown aetiology.

BACKGROUND: Acute limb ischaemia (ALI) is a limb and life-threatening condition with significant morbidity. There are currently no consensus recommendations for the investigative practices to determine the aetiology of ALI presenting without a known aetiology. We undertook a detailed analysis of all investigations performed to identify an underlying precipitant in those with unexplained ALI and formulated a suggested diagnostic algorithm for the evaluation of unexplained ALI. METHODS: ALI cases presenting to a tertiary referral centre over a 3-year period were reviewed, and known aetiologies, and investigations undertaken to determine the underlying aetiology of unexplained ALI were obtained. RESULTS: Unexplained ALI was found in 27 of 222 patients (12%), of which 21 (78%) had a cause for ALI established after further investigations. Six patients had no cause identified despite extensive work-up. Most patients with unexplained ALI had a cardioembolic source identified as the underlying cause (62%), and this included atrial fibrillation, infective endocarditis, cardiac myxoma and intra-cardiac thrombus. Other causes of unexplained ALI were detected by computed tomography (CT) imaging and included newly diagnosed significant atherosclerotic disease (19%), embolism from isolated proximal large vessel thrombus (10%) and metastatic malignancy (10%). There were no cases attributed to inherited thrombophilias, myeloproliferative neoplasms or anti-phospholipid syndrome. CONCLUSION: Among patients with unexplained ALI, the majority had a cardioembolic source highlighting the importance of comprehensive cardiac investigations. A subset of patients had alternative causes identified on CT imaging. These data support the use of a collaborative and integrative diagnostic algorithm in the evaluation of unexplained ALI.

Emerging Therapies for Recurrent Pericarditis: Interleukin-1 inhibitors.

Recurrent pericarditis (RP) is a complex inflammatory disorder associated with adverse outcomes and poor quality of life. After the first episode of acute pericarditis, a non-negligible group of patients will fail to achieve complete remission despite treatment and will be challenged by side effects from the chronic use of medications like corticosteroids. The cause of RP remains unknown in the majority of cases, mainly due to a gap in knowledge of its complex pathophysiology. Over the past 2 decades, the interleukin-1 (IL-1) pathway has been uncovered as a key element in the inflammatory cascade, allowing the development of pharmacological targets known as IL-1 inhibitors. This group of medications has emerged as a treatment option for patients with RP colchicine-resistance and steroid dependents. Currently, anakinra and rilonacept, have demonstrated beneficial impact in clinical outcomes with a reasonable safety profile in randomized clinical trials. There is still paucity of data regarding the use of canakinumab in the treatment of patients with RP. Although further studies are needed to refine therapeutic protocols and taper of concomitant therapies, IL-1 inhibitors, continue to consolidate as part of the pharmacological armamentarium to manage this complex condition with potential use as monotherapy. The aim of this review is to highlight the role of IL-1 pathway in RP and discuss the efficacy, safety, and clinical applicability of IL-1 inhibitors in the treatment of RP based on current evidence.

Prognostic Value of Complementary Echocardiography and Magnetic Resonance Imaging Quantitative Evaluation for Isolated Tricuspid Regurgitation.

BACKGROUND: Isolated tricuspid regurgitation (TR) remains a management dilemma with poor outcomes. Echocardiography and cardiac magnetic resonance imaging (CMR) are valuable tools for evaluating TR, but their prognostic utility has rarely been studied together in this setting. We aimed to determine the prognostic value and thresholds for echocardiography and CMR parameters for isolated severe TR. METHODS: Consecutive patients with isolated severe TR by echocardiography and undergoing CMR during January 2007 to June 2019 were studied. Echocardiography and CMR-derived quantitative parameters were analyzed for independent associations with and thresholds for predicting the primary end point of all-cause mortality during follow-up. RESULTS: Among 262 patients studied, mean age was 62.8±15.6 years, 156 (59.5%) were females, 207 (79.0%) had secondary TR, and 87 (33.2%) underwent tricuspid valve surgery after CMR. There were 68 (26.0%) deaths during a mean follow-up of 2.5 years. Both CMR-derived tricuspid regurgitant fraction (per 5% increase) and right ventricle free wall longitudinal strain (per 1% decrease in magnitude) were independently associated with worse survival, with hazard ratios (95% CIs) of 1.15 (1.05-1.25) and 1.10 (1.04-1.17), respectively, along with right heart failure symptoms of 2.03 (1.14-3.60), while tricuspid valve surgery was borderline protective with 0.55 (0.31-0.997). Regurgitant fraction ≥30%, regurgitant volume ≥35 mL and right ventricle free wall longitudinal strain ≥-11% (by velocity vector imaging technique, which yields lower magnitude values than other conventional strain techniques) were the optimal thresholds for mortality during follow-up. CONCLUSIONS: TR quantification by CMR and right ventricle free wall longitudinal strain by echocardiography were the key imaging parameters independently associated with reduced survival in isolated TR, incremental to conventional clinical factors. Clinically significant thresholds for these parameters were determined and may help guide decision-making for TR management.

Impact of Frailty and Mitral Valve Surgery on Outcomes of Severe Mitral Stenosis Due to Mitral Annular Calcification.

We sought to evaluate the outcomes of patients with severe mitral stenosis (MS) resulting from mitral annular calcification and assessed the prognostic impact of co-morbidities and frailty in guiding management. Among 6,915 patients with calcific MS who underwent echocardiography between January 2011 and March 2020, a total of 283 patients with severe calcific MS were retrospectively enrolled. We calculated the Charlson co-morbidity index (CCI). Frailty was scored from 0 to 3 points, with 1 point each assigned for reduced hemoglobin, reduced albumin, and inactivity. The primary end point was all-cause death. The mean age was 72 ± 11 years. The mean mitral valve (MV) area was 1.1 ± 0.4 cm2, and the mean transmitral gradient was 12 ± 4 mm Hg. Although 33% of the patients underwent MV intervention, 67% were conservatively managed. During a median follow-up of 360 days, 35% died. Patients who underwent MV intervention had an improved prognosis compared with those who were treated conservatively, even after propensity score matching. On multivariate Cox regression analysis, higher CCI (hazard ratio [HR] 1.20, 95% confidence interval [CI] 1.04 to 1.38, p = 0.011) and frailty score (HR 1.58, 95% CI 1.12 to 2.23, p = 0.01) were predictors of all-cause mortality, and MV intervention (HR 0.45, 95% CI 0.25 to 0.83, p = 0.011) and angiotensin converting enzyme inhibitor/angiotensin receptor blocker use (HR 0.39, 95% CI 0.20 to 0.79, p = 0.009) were associated with an improved prognosis. In conclusion, patients with severe calcific MS were often frail with multiple co-morbidities and were often managed conservatively. Higher CCI and worse frailty were associated with worse prognosis, regardless of the treatment strategy. MV intervention for select patients was associated with improved prognosis.

Epidemiology of biopsy-proven glomerulonephritis in Queensland adults.

AIM: There is a paucity of data pertaining to the incidence of biopsy-proven glomerulonephritis (GN) in Australia. This retrospective study aims to review the data from all adult native renal biopsies performed in the state of Queensland from 2002 to 2011--comparing results with centres from across the world. METHODS: Pathology reports of 3697 adult native kidney biopsies were reviewed, of which 2048 had GN diagnoses. Age, gender, clinical indication and histopathology findings were compared. RESULTS: The average age at biopsy was 48 ± 17 years. Male preponderance was noted overall (∼60%), with lupus nephritis being the only individual GN with female predilection. The average rate of biopsy was 12.04 per hundred thousand people per year (php/yr). Nephrotic and nephritic syndromes comprised approximately 75% of all clinical indications that lead to GN diagnoses. IgA nephropathy (1.41 php/yr) was the most common primary GN followed by focal segmental glomerulosclerosis (1.02 php/yr) and crescentic GN (0.73 php/yr). Diabetic nephropathy (0.84 php/yr), lupus nephritis (0.69 php/yr) and amyloidosis (0.19 php/yr) were the most commonly identified secondary GN. CONCLUSION: IgA nephropathy is the predominant primary GN in Queensland, and nephrotic syndrome the most common indication for a renal biopsy. While crescentic GN incidence has significantly increased with time, focal segmental glomerulosclerosis incidence has not shown any trend. Incidence of GN overall appears to increase with age. The annual rate of biopsy in this study appears lower than previously published in an Australian population.