Arrhythmia Recurrence After Atrial Fibrillation Ablation: Impact of Warfarin vs. Non-Vitamin K Antagonist Oral Anticoagulants.

PURPOSE: Both warfarin and non-vitamin K antagonist oral anticoagulants (NOACs) have pleiotropic effects including anti-inflammatory and anti-fibrotic properties. This study aims to explore whether arrhythmia recurrence after AF ablation is influenced by the choice of oral anticoagulant. METHODS: We retrospectively studied all patients who underwent primary AF ablation between 2011 and 2017 and divided them into two groups according to the anticoagulant used: Warfarin vs. NOACs. The primary endpoint was atrial tachyarrhythmia recurrence after ablation. RESULTS: Of the 1106 patients who underwent AF ablation in the study period (median age 62.5 years; 71.5% males, 48.2% persistent AF), 697 (63%) received warfarin and 409 (37%) received NOACs. After a median of 26.4 months follow-up, arrhythmia recurrence was noted in 368 patients in warfarin group and 173 patients in NOACs group, with a 1-year recurrence probability of 35% vs. 36% (log rank P = 0.81) and 5-year recurrence probability of 62% vs. 63% (Log rank P = 0.32). However, NOACs use was associated with a higher probability of recurrence (46% for 1 year, 68% for 5 years) in patients with persistent AF compared with those taking warfarin (34% for 1 year, 63% for 5 years; log rank P = 0.01 and P = 0.02 respectively). Multivariate analysis indicated that in patients with persistent AF, use of NOACs was an independent risk factor of atrial tachyarrhythmia recurrence after ablation (HR 1.39, 95% CI 1.07-1.81, P = 0.013). CONCLUSION: In this large contemporary cohort, overall AF recurrence after ablation was similar with NOACs or warfarin use. However, in patients with persistent AF, NOACs use was associated with a higher probability of arrhythmia recurrence and was an independent risk factor of recurrence at long-term follow-up.

Prognostic value of peak stress cardiac power in patients with normal ejection fraction undergoing exercise stress echocardiography.

AIMS: Cardiac power is a measure of cardiac performance that incorporates both pressure and flow components. Prior studies have shown that cardiac power predicts outcomes in patients with reduced left ventricular (LV) ejection fraction (EF). We sought to evaluate the prognostic significance of peak exercise cardiac power and power reserve in patients with normal EF. METHODS AND RESULTS: We performed a retrospective analysis in 24 885 patients (age 59 ± 13 years, 45% females) with EF ≥50% and no significant valve disease or right ventricular dysfunction, undergoing exercise stress echocardiography between 2004 and 2018. Cardiac power and power reserve (developed power with stress) were normalized to LV mass and expressed in W/100 g of LV myocardium. Endpoints at follow-up were all-cause mortality and diagnosis of heart failure (HF). Patients in the higher quartiles of power/mass (rest, peak stress, and power reserve) were younger and had higher peak blood pressure and heart rate, lower LV mass, and lower prevalence of comorbidities. During follow-up [median 3.9 (0.6-8.3) years], 929 patients died. After adjusting for age, sex, metabolic equivalents (METs) achieved, ischaemia/infarction on stress test results, medication, and comorbidities, peak stress power/mass was independently associated with mortality [adjusted hazard ratio (HR), highest vs. lowest quartile, 0.5, 95% confidence interval (CI) 0.4-0.6, P < 0.001] and HF at follow-up [adjusted HR, highest vs. lowest quartile, 0.4, 95% CI (0.3, 0.5), P < 0.001]. Power reserve showed similar results. CONCLUSION: The assessment of cardiac power during exercise stress echocardiography in patients with normal EF provides valuable prognostic information, in addition to stress test findings on inducible myocardial ischaemia and exercise capacity.

Post Procedural Peak Left Atrial Contraction Strain Predicts Recurrence of Arrhythmia after Catheter Ablation of Atrial Fibrillation.

BACKGROUND: Left atrial (LA) function can be impaired by the atrial fibrillation (AF) ablation and might be associated with the risk of recurrence. We sought to determine whether the post-procedural changes in LA function impact the risk of recurrence following AF ablation. METHODS: We retrospectively reviewed patients who underwent AF ablation between 2009 and 2011 and underwent transthoracic echocardiography before ablation, 1-day and 3-month after ablation. Peak left atrial contraction strain (PACS) and left atrial emptying fraction (LAEF) were evaluated during sinus rhythm and compared across the three time points. The primary endpoint was atrial tachyarrhythmia recurrence after ablation. RESULTS: A total of 144 patients were enrolled (mean age 61 ± 11 years, 77% male, 46% persistent AF). PACS and LAEF initially decreased 1-day following ablation but partially recovered within 3 months in PAF patients, with a similar trend in the PerAF patients. After median 24 months follow-up, 68 (47%) patients had recurrence. Patients with recurrence had higher PACS1-day than that in non-recurrence subjects (-10.9 ± 5.0% vs. -13.4 ± 4.7%, p = 0.003). PACS1-day -12% distinguished recurrence cases with a sensitivity of 67.7% and specificity of 60.5%. The Kaplan-Meier curves showed significant difference in 5-year cumulative probability of recurrence between those with PACS ≥ -12% and PACS < -12% (log rank p < 0.0001). Multivariate regression showed that PACS1-day was an independent risk factor of arrhythmia recurrence. CONCLUSIONS: Left atrial function deteriorates immediately following AF ablation and partially recovers in 3 months but remains abnormal in the majority of patients. PACS1-day post procedure predicts arrhythmia recurrence at long-term follow-up.

Cardiac remodeling in acute myocardial infarction: Prospective insights from multimodality ultrasound imaging.

BACKGROUND: The severity of MI declined markedly in the last decade, and contemporary patterns of cardiac remodeling after MI are not defined. METHODS: We prospectively enrolled community patients with first MI and performed comprehensive two- and three-dimensional echocardiography. Remodeling was defined as left ventricular (LV) end-systolic volume index (ESVI) above American Society of Echocardiography normal values. Remodeling patterns were characterized as an increase in LVESVI or LV end-diastolic volume index (LVEDVI), or both. RESULTS: Between 2014 and 2016, 213 patients (63±13 years; 34% women) were enrolled within 3 days after MI (77% non-ST-elevation MI). Acute remodeling was present in 51% of patients. Higher troponin and wall motion score index were associated with greater remodeling (p < 0.001). Atrial annular area, leaflet tenting and papillary muscle areas increased with greater remodeling (p < 0.001). The greater the cardiac remodeling, the lower the LV ejection fraction and global longitudinal strain (p < 0.001). This decrease in LV function was accompanied by stroke volume augmentation and maintenance of cardiac index at the expense of increased LVEDVI. Different remodeling patterns were identified. Cases showing increased LVEDVI and normal LVESVI had smallest infarct size and better hemodynamics compared to cases with augmented LVESVI and normal LVEDVI. CONCLUSION: Acute remodeling occurs in more than half of first MI cases and exhibits different patterns defined by cavity size and hemodynamic profile. Acute remodeling is a global phenomenon, which also involves the left atrium and the mitral apparatus.

Hemodynamics and Prognostic Impact of Concomitant Mitral Stenosis in Patients Undergoing Surgical or Transcatheter Aortic Valve Replacement for Aortic Stenosis.

BACKGROUND: Mitral stenosis frequently coexists in patients with severe aortic stenosis. Mitral stenosis severity evaluation is challenging in the setting of combined aortic stenosis and mitral stenosis because of hemodynamic interactions between the 2 valve lesions. The impact of aortic valve replacement (AVR) for severe aortic stenosis on mitral stenosis is unknown. This study aimed to assess the effect of AVR on mitral stenosis hemodynamics and the clinical outcomes of patients with severe aortic stenosis with and without mitral stenosis. METHODS: We retrospectively investigated patients who underwent surgical AVR or transcatheter AVR for severe aortic stenosis from 2008 to 2015. Mean transmitral gradient by Doppler echocardiography ≥4 mm Hg was identified as mitral stenosis; patients were then stratified according to mitral valve area (MVA, by continuity equation) as >2.0 cm2 or ≤2.0 cm2. MVA before and after AVR in patients with mitral stenosis were evaluated. Clinical outcomes of patients with and without mitral stenosis were compared using 1:2 matching for age, sex, left ventricular ejection fraction, method of AVR (surgical AVR versus transcatheter AVR) and year of AVR. RESULTS: Of 190 patients with severe aortic stenosis and mitral stenosis (age 76±9 years, 42% men), 184 were matched with 362 with severe aortic stenosis without mitral stenosis. Among all mitral stenosis patients, the mean MVA increased after AVR by 0.26±0.59 cm2 (from 2.00±0.50 to 2.26±0.62 cm2, P<0.01). MVA increased in 105 (55%) and remained unchanged in 34 (18%). Indexed stroke volume ≤45 mL/m2 (odds ratio [OR] 2.40; 95% CI, 1.15-5.01; P=0.020) and transcatheter AVR (OR, 2.36; 95% CI, 1.17-4.77; P=0.017) were independently associated with increase in MVA. Of 107 with significant mitral stenosis (MVA ≤2.0 cm2), MVA increased to >2.0 cm2 after AVR in 52 (49%, pseudo mitral stenosis) and remained ≤2.0 cm2 in 55 (51%, true mitral stenosis). During follow-up of median 2.9 (0.7-4.9) years, true mitral stenosis was an independent predictor of all-cause mortality (adjusted hazard ratio, 1.88; 95% CI, 1.20-2.94; P<0.01). CONCLUSIONS: MVA improved after AVR in nearly half of patients with severe aortic stenosis and mitral stenosis. MVA remained ≤2.0 cm2 (true mitral stenosis) in nearly half of patients with severe aortic stenosis and significant mitral stenosis; this was associated with worse survival among patients undergoing AVR for severe aortic stenosis.

Wave propagation of myocardial stretch: correlation with myocardial stiffness.

The mechanism of flow propagation during diastole in the left ventricle (LV) has been well described. Little is known about the associated waves propagating along the heart walls. These waves may have a mechanism similar to pulse wave propagation in arteries. The major goal of the study was to evaluate the effect of myocardial stiffness and preload on this wave transmission. Longitudinal late diastolic deformation and wave speed (Vp) of myocardial stretch in the anterior LV wall were measured using sonomicrometry in 16 pigs. Animals with normal and altered myocardial stiffness (acute myocardial infarction) were studied with and without preload alterations. Elastic modulus estimated from Vp (E VP; Moens-Korteweg equation) was compared to incremental elastic modulus obtained from exponential end-diastolic stress-strain relation (E SS). Myocardial distensibility and α- and ß-coefficients of stress-strain relations were calculated. Vp was higher at reperfusion compared to baseline (2.6 ± 1.3 vs. 1.3 ± 0.4 m/s; p = 0.005) and best correlated with E SS (r2 = 0.80, p < 0.0001), ß-coefficient (r2 = 0.78, p < 0.0001), distensibility (r2 = 0.47, p = 0.005), and wall thickness/diameter ratio (r2 = 0.42, p = 0.009). Elastic moduli (E VP and E SS) were strongly correlated (r2 = 0.83, p < 0.0001). Increasing preload increased Vp and E VP and decreased distensibility. At multivariate analysis, E SS, wall thickness, and end-diastolic and systolic LV pressures were independent predictors of Vp (r2 model = 0.83, p < 0.0001). In conclusion, the main determinants of wave propagation of longitudinal myocardial stretch were myocardial stiffness and LV geometry and pressure. This local wave speed could potentially be measured noninvasively by echocardiography.

Prognostic Significance of Elevated Left Ventricular Filling Pressures with Exercise: Insights from a Cohort of 14,338 Patients.

BACKGROUND: Exercise echocardiography can assess for cardiovascular causes of dyspnea other than coronary artery disease. However, the prevalence and prognostic significance of elevated left ventricular (LV) filling pressures with exercise is understudied. METHODS: We evaluated 14,338 patients referred for maximal symptom-limited treadmill echocardiography. In addition to assessment of LV regional wall motion abnormalities (RWMAs), we measured patients' early diastolic mitral inflow (E), septal mitral annulus relaxation (e'), and peak tricuspid regurgitation velocity before and immediately after exercise. RESULTS: Over a mean follow-up of 3.3 ± 3.4 years, patients with E/e' ≥15 with exercise (n = 1,323; 9.2%) had lower exercise capacity (7.3 ± 2.1 vs 9.1 ± 2.4 metabolic equivalents, P < .0001) and were more likely to have resting or inducible RWMAs (38% vs 18%, P < .0001). Approximately 6% (n = 837) had elevated LV filling pressures without RWMAs. Patients with a poststress E/e' ≥15 had a 2.71-fold increased mortality rate (2.28-3.21, P < .0001) compared with those with poststress E/e' ≤ 8. Those with an E/e' of 9 to 14, while at lower risk than the E/e' ≥15 cohort (hazard ratio [HR] = 0.58 [0.48-0.69]; P < .0001), had higher risk than if E/e' ≤8 (HR = 1.56 [1.37-1.78], P < .0001). On multivariable analysis, adjusting for age, sex, exercise capacity, LV ejection fraction, and presence of pulmonary hypertension with stress, patients with E/e' ≥15 had a 1.39-fold (95% CI, 1.18-1.65, P < .0001) increased risk of all-cause mortality compared with patients without elevated LV filling pressures. Compared with patients with E/e' ≤ 15 after exercise, patients with E/e' ≤15 at rest but elevated after exercise had a higher risk of cardiovascular death (HR = 8.99 [4.7-17.3], P < .0001). CONCLUSION: Patients with elevated LV filling pressures are at increased risk of death, irrespective of myocardial ischemia or LV systolic dysfunction. These findings support the routine incorporation of LV filling pressure assessment, both before and immediately following stress, into the evaluation of patients referred for exercise echocardiography.

Low Pulmonary Artery Pulsatility Index by Echocardiography Is Associated With Increased Mortality in Pulmonary Hypertension.

BACKGROUND: Pulmonary hypertension (PH) is a progressive pulmonary vascular disorder with elevated mortality risk. The pulmonary artery (PA) pulsatility index (PAPi) based on invasively acquired parameters has emerged as a hemodynamic risk predictor. Whether noninvasively derived PAPi (PA pulse pressure divided by right atrial pressure) is valuable is unclear. METHODS: Consecutive patients undergoing transthoracic echocardiography for known or suspected PH were included with conventional echocardiographic measures of PA systolic, PA diastolic, and estimated right atrial pressures. In those patients with PH (mean PA pressure > 20 mm Hg), PAPi was divided into 3 groups: <1.5, 1.5 to 3, and >3. Mortality was assessed over 5 years. RESULTS: Of 1,045 patients enrolled, 64% had PH. Patients with the lowest PAPi had higher N-terminal-pro hormone B-type natriuretic peptide levels, larger right ventricles (RVs), worse RV systolic function, and greater degrees of tricuspid regurgitation. In patients with PH, PAPi was inversely proportional to the risk of death, with PAPi <3 associated with a 1.96-fold increased risk of death (95% CI, 1.45-2.64, P < .0001). At multivariate analysis, RV longitudinal systolic strain (hazard ratio [HR] = 1.45, 1.24-1.71; P < .0001), PAPi <3 (HR = 1.76, 1.31-2.37; P = .0002), and the presence of a pericardial effusion (HR = 1.64, 1.20-2.26 P = .003) were independently associated with increased mortality. In age- and sex-adjusted models, PAPi was incremental to PA compliance. CONCLUSIONS: In patients with PH, low PAPi derived noninvasively by transthoracic echocardiography is associated with markers of right heart failure, RV dysfunction, and worse survival. PAPi could be incorporated into the conventional echo parameters reported in patients with PH and may be a useful predictor of outcome.

The 5 Phenotypes of Tricuspid Regurgitation: Insight From Cluster Analysis of Clinical and Echocardiographic Variables.

BACKGROUND: The recent morphologic classification of tricuspid regurgitation (TR) (ie, atrial functional, ventricular functional, lead related, and primary) does not capture underlying comorbidities and clinical characteristics. OBJECTIVES: This study aimed to identify the different phenotypes of TR using unsupervised cluster analysis and to determine whether differences in clinical outcomes were associated with these phenotypes. METHODS: We included 13,611 patients with ≥moderate TR from January 2004 to April 2019 in the final analyses. Baseline demographic, clinical, and echocardiographic data were obtained from electronic medical records and echocardiography reports. Ward's minimum variance method was used to cluster patients based on 38 variables. The analysis of all-cause mortality was performed using the Kaplan-Meier method, and groups were compared using log-rank test. RESULTS: The mean age of patients was 72 ± 13 years, and 56% were women. Cluster analysis identified 5 distinct phenotypes: cluster 1 represented "low-risk TR" with less severe TR, a lower prevalence of right ventricular enlargement, atrial fibrillation, and comorbidities; cluster 2 represented "high-risk TR"; and clusters 3, 4, and 5 represented TR associated with lung disease, coronary artery disease, and chronic kidney disease, respectively. Cluster 1 had the lowest mortality followed by clusters 2 (HR: 2.22 [95% CI: 2.1-2.35]; P < 0.0001) and 4 (HR: 2.19 [95% CI: 2.04-2.35]; P < 0.0001); cluster 3 (HR: 2.45 [95% CI: 2.27-2.65]; P < 0.0001); and, lastly, cluster 5 (HR: 3.48 [95% CI: 3.07-3.95]; P < 0.0001). CONCLUSIONS: Cluster analysis identified 5 distinct novel subgroups of TR with differences in all-cause mortality. This phenotype-based classification improves our understanding of the interaction of comorbidities with this complex valve lesion and can inform clinical decision making.

Pulmonary artery pulsatility index in patients with tricuspid valve regurgitation: a simple non-invasive tool for risk stratification.

AIMS: Tricuspid valve regurgitation (TR) is a common valvular disease associated with increased mortality. There is a need for tools to assess the interaction between the pulmonary artery (PA) circulation and the right ventricle in patients with TR and to investigate their association with outcomes. The pulmonary artery pulsatility index (PAPi) has emerged as a haemodynamic risk predictor in left heart disease and pulmonary hypertension (PH). Whether PAPi discriminates risk in unselected patients with greater than or equal to moderate TR is unknown. METHODS AND RESULTS: In 5079 patients with greater than or equal to moderate TR (regardless of aetiology) and PA systolic and diastolic pressures measured on their first echocardiogram, we compared all-cause mortality at 5 years based on the presence or absence of PH and PAPi levels. A total of 2741 (54%) patients had PH. The median PAPi was 3.0 (IQR 1.9, 4.4). Both the presence of PH and decreasing levels of PAPi were associated with larger right ventricles, worse right ventricular systolic function, higher NT-pro BNP levels, greater degrees of right heart failure, and worse survival. In a subset of patients who had an echo and right heart catheterization within 24 h, the correlation of non-invasive to invasive PA pressures and PAPi levels was very good (r = 0.76). CONCLUSION: In patients with greater than or equal to moderate TR with and without PH, lower PAPi is associated with right ventricular dysfunction, right heart failure, and worse survival. Incorporating PA pressure and PAPi may help stratify disease severity in patients with greater than or equal to moderate TR regardless of aetiology.