Arrythmia-Mediated Valvular Heart Disease.

The aging population is rising at record pace worldwide. Along with it, a steep increase in the prevalence of atrial fibrillation and heart failure with preserved ejection fraction is to be expected. Similarly, both atrial functional mitral and tricuspid regurgitation (AFMR and AFTR) are increasingly observed in daily clinical practice. This article summarizes all current evidence regarding the epidemiology, prognosis, pathophysiology, and therapeutic options. Specific attention is addressed to discern AFMR and AFTR from their ventricular counterparts, given their different pathophysiology and therapeutic needs.

Prognostic importance of the transmitral pressure gradient in mitral annular calcification with associated mitral valve dysfunction.

AIMS: The aim of this study was to define the natural history of patients with mitral annular calcification (MAC)-related mitral valve dysfunction and to assess the prognostic importance of mean transmitral pressure gradient (MG) and impact of concomitant mitral regurgitation (MR). METHODS AND RESULTS: The institutional echocardiography database was examined from 2001 to 2019 for all patients with MAC and MG ≥3 mmHg. A total of 5754 patients were stratified by MG in low (3-5 mmHg, n = 3927), mid (5-10 mmHg, n = 1476), and high (≥10 mmHg, n = 351) gradient. The mean age was 78 ± 11 years, and 67% were female. MR was none/trace in 32%, mild in 42%, moderate in 23%, and severe in 3%. Primary outcome was all-cause mortality, and outcome models were adjusted for age, sex, and MAC-related risk factors (hypertension, diabetes, coronary artery disease, chronic kidney disease). Survival at 1, 5, and 10 years was 77%, 42%, and 18% in the low-gradient group; 73%, 38%, and 17% in the mid-gradient group; and 67%, 25%, and 11% in the high-gradient group, respectively (log-rank P < 0.001 between groups). MG was independently associated with mortality (adjusted HR 1.064 per 1 mmHg increase, 95% CI 1.049-1.080). MR severity was associated with mortality at low gradients (P < 0.001) but not at higher gradients (P = 0.166 and 0.372 in the mid- and high-gradient groups, respectively). CONCLUSION: In MAC-related mitral valve dysfunction, mean transmitral gradient is associated with increased mortality after adjustment for age, sex, and MAC-related risk factors. Concomitant MR is associated with excess mortality in low-gradient ranges (3-5 mmHg) but gradually loses prognostic importance at higher gradients, indicating prognostic utility of transmitral gradient in MAC regardless of MR severity.

Dual antiplatelet therapy after percutaneous left atrial appendage occlusion: single center experience with the Amplatzer Cardiac Plug.

BACKGROUND: Percutaneous left atrial appendage occlusion (LAAO) is an alternative to anticoagulation in atrial fibrillation patients at high bleeding risk. Dual antiplatelet therapy (DAPT) is generally recommended in the months following the procedure to prevent thrombotic complications. The aim of this study was to evaluate the safety and efficacy of DAPT after LAAO in a single-centre population of high bleeding risk patients. METHODS: All patients who received DAPT after LAAO using the Amplatzer Cardiac Plug at Jessa Hospital (Hasselt, BE) between February 2011 and October 2016 were included. Patient characteristics, procedural outcome and clinical events (bleeding, stroke and adverse events) were prospectively followed. Changes in antithrombotic and/or anticoagulant regimens were assessed. RESULTS: Thirty-nine patients (77 ± 7 years, 51% male, CHA2DS2-VASc 5(3-6), Hypertension, Abnormal Renal/Liver Function, Stroke, Bleeding History or Predisposition, Labile INR, Elderly, Drugs/Alcohol Concomitantly (HAS-BLED) 3(3-4)) were included. An initial strategy of one month DAPT (n = 2) was changed to six months DAPT (n = 37) after one thrombotic complication (device thrombosis) at 4.5 months. Post-procedural DAPT duration was 6.1 ± 3.7 months, after which aspirin monotherapy (62%), no antiplatelet/anticoagulant therapy (15%) or a tailored antithrombotic regimen was maintained. At mean follow-up of 21 ± 13 months, seven patients had died (18%), no strokes had occurred (0%) and nine bleedings of which four were major (10%). All major bleedings occurred within the first six months after the procedure during DAPT. CONCLUSION: Antithrombotic therapy after percutaneous LAAO is needed to prevent thrombotic complications, yet these impose bleeding complications in this high-risk population. Further efforts are needed to define the optimal duration of DAPT, aimed at reducing bleeding complications while maintaining a low thrombosis rate.

Exercise Dynamics in Secondary Mitral Regurgitation: Pathophysiology and Therapeutic Implications.

Secondary mitral valve regurgitation (MR) remains a challenging problem in the diagnostic workup and treatment of patients with heart failure. Although secondary MR is characteristically dynamic in nature and sensitive to changes in ventricular geometry and loading, current therapy is mainly focused on resting conditions. An exercise-induced increase in secondary MR, however, is associated with impaired exercise capacity and increased mortality. In an era where a multitude of percutaneous solutions are emerging for the treatment of patients with heart failure, it becomes important to address the dynamic component of secondary MR during exercise as well. A critical reappraisal of the underlying disease mechanisms, in particular the dynamic component during exercise, is of timely importance. This review summarizes the pathophysiological mechanisms involved in the dynamic deterioration of secondary MR during exercise, its functional and prognostic impact, and the way current treatment options affect the dynamic lesion and exercise hemodynamics in general.

Feasibility and Association of Neurohumoral Blocker Up-titration After Cardiac Resynchronization Therapy.

BACKGROUND: Cardiac resynchronization therapy (CRT) improves mortality and morbidity on top of optimal medical therapy in heart failure with reduced ejection fraction (HFrEF). This study aimed to elucidate the association between neurohumoral blocker up-titration after CRT implantation and clinical outcomes. METHODS AND RESULTS: Doses of angiotensin-converting enzyme inhibitors (ACE-Is), angiotensin receptor blockers (ARBs), and beta-blockers were retrospectively evaluated in 650 consecutive CRT patients implanted from October 2008 to August 2015 and followed in a tertiary multidisciplinary CRT clinic. All 650 CRT patients were on a maximal tolerable dose of ACE-I/ARB and beta-blocker at the time of CRT implantation. However, further up-titration was successful in 45.4% for ACE-I/ARB and in 56.8% for beta-blocker after CRT-implantation. During a mean follow-up of 37 ± 22 months, a total of 139 events occurred for the combined end point of heart failure admission and all-cause mortality. Successful, versus unsuccessful, up-titration was associated with adjusted hazard ratios of 0.537 (95% confidence interval 0.316-0.913; P = .022) for ACE-I/ARB and 0.633 (0.406-0.988; P = .044) for beta-blocker on the combined end point heart failure admission and all-cause mortality. Patients in the up-titration group exhibited a similar risk for death or heart failure admission as patients treated with the maximal dose (ACE-I/ARB: P = .133; beta-blockers: P = .709). CONCLUSIONS: After CRT, a majority of patients are capable of tolerating higher dosages of neurohumoral blockers. Up-titration of neurohumoral blockers after CRT implantation is associated with improved clinical outcomes, similarly to patients treated with the guideline-recommended target dose at the time of CRT implantation.

Plasma Volume Is Normal but Heterogeneously Distributed, and True Anemia Is Highly Prevalent in Patients With Stable Heart Failure.

BACKGROUND: Intravascular volume overload and depletion as well as anemia are associated with increased hospital admissions and mortality in patients with heart failure. This study aimed to accurately measure plasma volume and red cell mass (RCM) in stable patients with chronic heart failure with reduced ejection fraction (HFrEF) and gain more insight into plasma volume regulation and anemia in stable conditions of HFrEF. METHODS AND RESULTS: Plasma volume and RCM measurement based on 99Tc-labeled red blood cells, venous blood sample,s and clinical parameters were obtained in 24 stable HFrEF patients under optimal medical therapy. Measured plasma volume values were compared with predicted values based on body surface area. Plasma volume was on average normal (99.98% of predicted) but heterogeneously distributed (variations of 81%-133%). Neurohumoral activation and medication use were not associated with plasma volume status. Furthermore, anemia based on actual measurement of RCM was present in up to 75% of subjects, but rarely hemodilutional. CONCLUSIONS: In stable chronic HFrEF patients under optimal medical therapy, plasma volume is overall normal but heterogeneously distributed. Anticipated factors such as neurohumoral activation and heart failure medication were not associated with plasma volume. Furthermore, anemia is more common than as assessed by hemoglobin.

The figure-of-eight artifact in the echocardiographic assessment of percutaneous disc occluders: impact of imaging depth and device type.

PURPOSE: Echocardiography is increasingly important in the guidance and follow-up of percutaneous transcatheter device closures. It was recently shown that the Amplatzer left atrial appendage occluder frequently presents as a figure-of-eight artifact due to interaction of device mesh and ultrasound waves. It remains unknown whether this can be translated to other types of disc occluders. Furthermore, the morphology of this figure-of-eight artifact appears to be different in the transesophageal and transthoracic image of the same device. The aim of this study was to evaluate the echocardiographic appearance of different types of disc occluders, and to clarify differences in morphology of the figure-of-eight artifact. METHODS: A mathematical model of an epitrochoid curve was used for numerical simulation of disc occluder appearance at various imaging depths. In addition, an in vitro setup was used for echocardiographic analysis of different types of disc occluders at adjustable imaging depth and position. RESULTS: Mathematically, decreasing the imaging depth resulted in a more asymmetric figure-of-eight, i.e. with small upper part and wide lower part. In vitro results were in close agreement with the mathematical results. In addition, in vitro a figure-of-eight artifact was obtained in all different types of disc occluder devices. CONCLUSIONS: Different types of percutaneous disc occluders all present as a figure-of-eight artifact on echocardiography when imaged from a coronal imaging position. The morphology of the artifact depends on the imaging depth, with a more asymmetric figure-of-eight morphology at smaller probe-to-device distance. This clarifies the differences observed between transesophageal and transthoracic imaging.

Determinants and impact of the natriuretic response to diuretic therapy in heart failure with reduced ejection fraction and volume overload.

OBJECTIVE: The objective of this study was to investigate determinants of the natriuretic response to diuretics in decompensated heart failure (HF) and the relationship with decongestion, neurohumoral activation and clinical outcome in the contemporary era of HF management. METHODS AND RESULTS: In this prospective, single-centre cohort study, consecutive patients with decompensated HF (n = 54) and left ventricular ejection fraction 45% received protocol-driven diuretic therapy until complete disappearance of congestion signs. Urine was collected during three consecutive 24-h intervals. Natriuretic response was defined as absolute natriuresis (mmol) per mg of intravenous bumetanide administered. Natriuresis was 146 mmol (76-206 mmol), 74 mmol (37-167 mmol) and 74 mmol (53-134 mmol) per mg intravenous bumetanide administered during the first, second and third 24-h interval, respectively. Diastolic blood pressure (beta = 23.048 +/- 10.788; P-value = 0.036), plasma aldosterone (beta = -25.722?11.560; P-value=0.029), and combination therapy with acetazolamide (beta = 103.241 +/- 40.962; P-value = 0.014) were independent predictors of the natriuretic response. Patients with a stronger natriuretic response demonstrated more pronounced decreases in plasma NT-proBNP levels (P-value = 0.025), while a weaker response was associated with higher peak plasma aldosterone levels (P-value = 0.013) and plasma renin activity (P-value = 0.033). Natriuresis per loop diuretic dose predicted freedom from all-cause mortality or HF readmissions, independently of baseline renal function (HR 0.40, 95% CI 0.16-0.98; P-value = 0.045). CONCLUSIONS: More effective natriuresis in decompensated HF patients with reduced ejection fraction and volume overload is associated with better decongestion, less neurohumoral activation and predicts favourable clinical outcome independently from renal function per se. Acetazolamide warrants further evaluation in large prospective trials to increase the natriuretic response to loop diuretics.

Pulmonary homograft endocarditis and aortic autograft failure after Ross procedure: a double stentless bioprosthesis approach.

The case is reported of a 38-year-old male patient with pulmonary homograft acute infective endocarditis and aortic root dilation that occurred 13 years after a Ross procedure for bicuspid aortic valve regurgitation. Aortic and pulmonary root replacements were performed, using a Freestyle stentless aortic root bioprosthesis in both cases, with excellent hemodynamics on postoperative echocardiography. In addition, preoperative systemic septic embolization had occurred despite an absence of left-sided endocarditis, presumably due to an intrapulmonary shunt. This case report demonstrates the feasibility of a double stentless bioprosthesis approach, and stresses the need to remain vigilant for septic embolization even in isolated right-sided endocarditis.

Altered mitral inflow orifice in severe aortic regurgitation: real time three-dimensional echocardiographic findings.

We present the case of a young man with severe eccentric aortic regurgitation, obstructing mitral inflow and provoking an audible Austin Flint murmur at clinical examination. Two-dimensional color Doppler echocardiography depicts the remarkable mechanical interaction between aortic regurgitant jet and anterior mitral leaflet opening. Three-dimensional transesophageal echocardiography aids in understanding the geometric and hemodynamic consequences of the regurgitant jet and in the genesis of the Austin Flint murmur. This case accentuates the incremental value of three-dimensional echocardiography when evaluating valvular pathology, and offers more insight in the interaction between aortic regurgitant flow and mitral leaflet dynamics.

Exercise-Induced Pulmonary Hypertension: Rationale for Correcting Pressures for Flow and Guide to Non-Invasive Diagnosis.

Exercise-induced pulmonary hypertension (exPHT) is a hemodynamic condition linked to increased morbidity and mortality across various cardiopulmonary diseases. Traditional definitions of exPHT rely on absolute cut-offs, such as mean pulmonary artery pressure (mPAP) above 30 mmHg during exercise. However, recent research suggests that these cut-offs may not accurately reflect pathophysiological changes, leading to false positives and false negatives. Instead, the mPAP over cardiac output (CO) slope, which incorporates both pressure and flow measurements, has emerged as a more reliable indicator. A slope exceeding 3 mmHg/L/min is now considered diagnostic for exPHT and strongly correlates with adverse outcomes. Stress echocardiography serves as a viable alternative to invasive assessment, enabling broader implementation. This review discusses the physiological basis of pulmonary hemodynamics during exercise, the advantages of the mPAP/CO slope over absolute pressure measurements, the evidence supporting its inclusion in clinical guidelines, and provides a practical guide for non-invasive determining the mPAP/CO slope in clinical practice.

Non-invasive imaging in acute decompensated heart failure with preserved ejection fraction.

Non-invasive imaging plays an increasingly important role in emergency medicine, given the trend towards smaller, portable ultrasound devices, the integration of ultrasound imaging across diverse medical disciplines, and the growing evidence supporting its clinical benefits for the patient. Heart failure with preserved ejection fraction (HFpEF) provides a compelling illustration of the impactful role that imaging plays in distinguishing diverse clinical presentations of heart failure with numerous associated comorbidities, including pulmonary, renal, or hepatic diseases. While a preserved left ventricular ejection fraction might misguide the clinician away from diagnosing cardiac disease, there are several clues provided by cardiac, vascular, and lung ultrasonography, as well as other imaging modalities, to rapidly identify (decompensated) HFpEF. Congestion remains the primary reason why patients with heart failure (irrespective of ejection fraction) seek emergency care. Furthermore, comprehensive phenotyping is becoming increasingly important, considering the development of targeted treatments for conditions exhibiting HFpEF physiology, such as cardiac amyloidosis. Timely recognition in such cases has lasting implications for long-term outcomes.

Exercise pulmonary hypertension by the mPAP/CO slope in primary mitral regurgitation.

AIMS: Exercise-induced pulmonary hypertension (PH), defined by a mean pulmonary arterial pressure over cardiac output (mPAP/CO) slope >3 mmHg/L/min, has important diagnostic and prognostic implications. The aim of this study is to investigate the value of the mPAP/CO slope in patients with more than moderate primary mitral regurgitation (MR) with preserved ejection fraction and no or discordant symptoms. METHODS AND RESULTS: A total of 128 consecutive patients were evaluated with exercise echocardiography and cardiopulmonary testing. Clinical outcome was defined as the composite of mitral valve intervention, new-onset atrial fibrillation, cardiovascular hospitalization, and all-cause mortality. The mean age was 63 years, 61% were male, and the mean LVEF was 66 ± 6%. The mPAP/CO slope correlated with peak VO2 (r = -0.52, P < 0.001), while the peak systolic pulmonary artery pressure (sPAP) did not (r = -0.06, P = 0.584). Forty-six per cent (n = 59) had peak exercise sPAP ≥60 mmHg, and 37% (n = 47) had mPAP/CO slope >3 mmHg/L/min. Event-free survival was 55% at 1 year and 46% at 2 years, with reduced survival in patients with mPAP/CO slope >3 mmHg/L/min (hazard ratio, 4.9; 95% confidence interval, 2.9-8.2; P < 0.001). In 53 cases (41%), mPAP/CO slope and peak sPAP were discordant: patients with slope >3 mmHg/L/mmHg and sPAP <60 mmHg (n = 21) had worse outcome vs. peak sPAP ≥60 mmHg and normal slope (n = 32, log-rank P = 0.003). The mPAP/CO slope improved predictive models for outcome, incremental to resting and exercise sPAP, and peak VO2. CONCLUSION: Exercise PH defined by the mPAP/CO slope >3 mmHg/L/min is associated with decreased exercise capacity and a higher risk of adverse events in significant primary MR and no or discordant symptoms. The slope provides a greater prognostic value than single sPAP measures and peak VO2.

Mitral regurgitation in heart failure with preserved ejection fraction: The interplay of valve, ventricle, and atrium.

Mitral regurgitation (MR) is highly prevalent among patients with heart failure and preserved ejection fraction (HFpEF). Despite this combination being closely associated with unfavourable outcomes, it remains relatively understudied. This is partly due to the inherent heterogeneity of patients with HFpEF. To address this gap, dissecting HFpEF into mechanism-based phenotypes may offer a promising avenue for advancing our comprehension of these complex intertwined conditions. This review employs the validated CircAdapt model to explore the haemodynamic implications of moderate to severe MR across a well-defined spectrum of myocardial disease, characterized by impaired relaxation and reduced myocardial compliance. Both heart failure and mitral valve disease share overlapping symptomatology, primarily attributed to elevated pulmonary pressures. The intricate mechanisms contributing to these elevated pressures are multifaceted, potentially influenced by diastolic dysfunction, left atrial myopathy, and MR. Accurate evaluation of the haemodynamic and clinical impact of MR necessitates a comprehensive approach, taking into account the characteristics of both the left atrium and left ventricle, as well as their intricate interactions, which may currently be underemphasized in diagnostic practice. This holistic assessment is imperative for enhancing our understanding and refining therapeutic strategies within this patient cohort.

Mitral Valve Surgery for Mitral Regurgitation Results in Reduced Left Ventricular Ejection Fraction in Barlow's Disease as Compared with Fibro-Elastic Deficiency.

Surgical correction of severe mitral regurgitation (MR) can reverse left ventricular (LV) remodeling in patients with mitral valve prolapse (MVP). However, whether this process is similar to the case in Barlow's Disease (BD) and Fibro-elastic Deficiency (FED) is currently unknown. The aim of this study is to evaluate post-operative LV reverse remodeling and function in patients with BD versus FED. In this study, 100 MVP patients (BD = 37 and FED = 63) with severe MR who underwent mitral valve surgery at three Belgian centers were retrospectively included. Transthoracic echocardiography was used to assess MR severity, LV volumes and function before surgery and 6 months thereafter. Baseline MR severity, LV ejection fraction (LVEF), indexed LV end-diastolic (LVEDVi) and end-systolic volumes (LVESVi) were not different between the groups. After a median follow-up of 278 days, there was a similar decrease in LVEDVi, but a trend towards a smaller decrease in LVESVi in BD compared to FED (-3.0 ± 11.2 mL/m2 vs. -5.3 ± 9.0 mL/m2; p = 0.154). This resulted in a significantly larger decrease in LVEF in BD (-8.3 ± 9.6%) versus FED (-3.9 ± 6.9%) after adjusting for baseline LVEF (p < 0.001) and type of surgical intervention (p = 0.01). These findings suggest that LV (reverse) remodeling in BD could be affected by other mechanisms beyond volume overload, potentially involving concomitant cardiomyopathy.

Clinical Significance of Exercise Pulmonary Hypertension With a Negative Diastolic Stress Test for Suspected Heart Failure With Preserved Ejection Fraction.

BACKGROUND: Half of patients with heart failure with preserved ejection fraction (HFpEF) remain undiagnosed by resting evaluation alone. Therefore, exercise testing is proposed. The diastolic stress test (DST), however, has limited sensitivity. We aimed to determine the clinical significance of adding the mean pulmonary artery pressure over cardiac output (mPAP/CO) slope to the DST in suspected HFpEF. METHODS AND RESULTS: In this prospective cohort study, consecutive patients (n=1936) with suspected HFpEF underwent exercise echocardiography with simultaneous respiratory gas analysis. These patients were stratified by exercise E over e' (exE/e') and mPAP/CO slope, and peak oxygen uptake, natriuretic peptides (NT-proBNP [N-terminal pro-B-type natriuretic peptide]), and score-based HFpEF likelihood were compared. Twenty-two percent of patients (n=428) had exE/e'<15 despite a mPAP/CO slope>3 mm Hg/L per min, 24% (n=464) had a positive DST (exE/e'≥15), and 54% (n=1044) had a normal DST and slope. Percentage of predicted oxygen uptake was similar in the group with exE/e'<15 but high mPAP/CO slope and the positive DST group (-2% [-5% to +1%]), yet worse than in those with normal DST and slope (-12% [-14% to -9%]). Patients with exE/e'<15 but a high slope had NT-proBNP levels and H2FPEF (heavy, hypertensive, atrial fibrillation, pulmonary hypertension, elder; filling pressure) scores intermediate to the positive DST group and the group with both a normal DST and slope. CONCLUSIONS: Twenty-two percent of patients with suspected HFpEF presented with a mPAP/CO slope>3 mm Hg/L per min despite a negative DST. These patients had HFpEF characteristics and a peak oxygen uptake as low as patients with a positive DST. Therefore, an elevated mPAP/CO slope might indicate HFpEF irrespective of the DST result.

Diagnostic Value of Aortic Valve Calcification Levels in the Assessment of Low-Gradient Aortic Stenosis.

BACKGROUND: In patients with low-gradient aortic stenosis (AS) and low transvalvular flow, dobutamine stress echocardiography (DSE) is recommended to determine AS severity, whereas the degree of aortic valve calcification (AVC) supposedly correlates with AS severity according to current European and American guidelines. OBJECTIVES: The purpose of this study was to assess the relationship between AVC and AS severity as determined using echocardiography and DSE in patients with aortic valve area <1 cm2 and peak aortic valve velocity <4.0 m/s. METHODS: All patients underwent DSE to determine AS severity and multislice computed tomography to quantify AVC. Receiver-operating characteristics curve analysis was used to assess the diagnostic value of AVC for AS severity grading as determined using echocardiography and DSE in men and women. RESULTS: A total of 214 patients were included. Median age was 78 years (25th-75th percentile: 71-84 years) and 25% were women. Left ventricular ejection fraction was reduced (<50%) in 197 (92.1%) patients. Severe AS was diagnosed in 106 patients (49.5%). Moderate AS was diagnosed in 108 patients (50.5%; in 77 based on resting transthoracic echocardiography, in 31 confirmed using DSE). AVC score was high (≥2,000 for men or ≥1,200 for women) in 47 (44.3%) patients with severe AS and in 47 (43.5%) patients with moderate AS. AVC sensitivity was 44.3%, specificity was 56.5%, and positive and negative predictive values for severe AS were 50.0% and 50.8%, respectively. Area under the receiver-operating characteristics curve was 0.508 for men and 0.524 for women. CONCLUSIONS: Multi-slice computed tomography-derived AVC scores showed poor discrimination between grades of AS severity using DSE and cannot replace DSE in the diagnostic work-up of low-gradient severe AS.

Reduced Left Atrial Appendage Flow Is Associated With Future Atrial Fibrillation After Cryptogenic Stroke.

BACKGROUND: Hemostasis within the left atrial appendage (LAA) is a common cause of stroke, especially in patients with atrial fibrillation (AF). Although LAA flow provides insights into LAA function, its potential for predicting AF has yet to be established. The aim of this study was to explore whether LAA peak flow velocities early after cryptogenic stroke are associated with future AF on prolonged rhythm monitoring. METHODS: A total of 110 patients with cryptogenic stroke were consecutively enrolled and underwent LAA pulsed-wave Doppler flow assessment using transesophageal echocardiography within the early poststroke period. Velocity measurements were analyzed offline by an investigator blinded to the results. Prolonged rhythm monitoring was conducted on all participants via 7-day Holter and implantable cardiac monitoring devices, with follow-up conducted over a period of 1.5 years to determine the incidence of AF. The end point of AF was defined as irregular supraventricular rhythm with variable RR interval and no detectable P waves lasting ≥30 sec during rhythm monitoring. RESULTS: During a median follow-up period of 539 days (interquartile range, 169-857 days), 42 patients (38%) developed AF, with a median time to AF diagnosis of 94 days (interquartile range, 51-487 days). Both LAA filling velocity and LAA emptying velocity (LAAev) were lower in patients with AF (44.3 ± 14.2 and 50.7 ± 13.3 cm/s, respectively) compared with patients without AF (59.8 ± 14.0 and 76.8 ± 17.3 cm/sec, respectively; P < .001 for both). LAAev was most strongly associated with future AF, with an area under the receiver operating characteristic curve of 0.88 and an optimal cutoff value of 55 cm/sec. Age and mitral regurgitation were independent determinants of reduced LAAev. CONCLUSIONS: Impaired LAA peak flow velocities (LAAev < 55 cm/sec) in patients with cryptogenic stroke are associated with future AF. This may facilitate the selection of appropriate candidates for prolonged rhythm monitoring to improve its diagnostic accuracy and implementation.

Sex Differences in Extensive Mitral Annular Calcification With Associated Mitral Valve Dysfunction.

Mitral annular calcification (MAC)-related mitral valve (MV) dysfunction is an increasingly recognized entity, which confers a high burden of morbidity and mortality. Although more common among women, there is a paucity of data regarding how the phenotype of MAC and the associated adverse clinical implications may differ between women and men. A total of 3,524 patients with extensive MAC and significant MAC-related MV dysfunction (i.e., transmitral gradient ≥3 mm Hg) were retrospectively analyzed from a large institutional database, with the goal of defining gender differences in clinical and echocardiographic characteristics and the prognostic importance of MAC-related MV dysfunction. We stratified patients into low- (3 to 5 mm Hg), moderate- (5 to 10 mm Hg), and high- (≥10 mm Hg) gradient groups and analyzed the gender differences in phenotype and outcome. The primary outcome was all-cause mortality, assessed using adjusted Cox regression models. Women represented the majority (67%) of subjects, were older (79.3 ± 10.4 vs 75.5 ± 10.9 years, p <0.001) and had a lower burden of cardiovascular co-morbidities than men. Women had higher transmitral gradients (5.7 ± 2.7 vs 5.3 ± 2.6 mm Hg, p <0.001), more concentric hypertrophy (49% vs 33%), and more mitral regurgitation. The median survival was 3.4 years (95% confidence interval 3.0 to 3.6) among women and 3.0 years (95% confidence interval 2.6 to 4.5) among men. The adjusted survival was worse among men, and the prognostic impact of the transmitral gradient did not differ overall by gender. In conclusion, we describe important gender differences among patients with MAC-related MV dysfunction and show worse adjusted survival among men; although, the adverse prognostic impact of the transmitral gradient was similar between men and women.