Nurse-led diuretic titration via a point-of-care urinary sodium sensor in patients with acute decompensated heart failure (EASY-HF): A single-centre, randomized, open-label study.

AIMS: Early evaluation of the natriuretic response is recommended to guide diuretic therapy in acute decompensated heart failure (ADHF). However, its implementation in daily practice is hampered by implementation barriers and increased time constraints. The Readily Available Urinary Sodium Analysis in Patients with Acute Decompensated Heart Failure (EASY-HF) study assessed the feasibility, efficacy and safety of a nurse-led urinary sodium-based diuretic titration protocol with the use of a point-of-care urinary sodium sensor. METHODS AND RESULTS: The EASY-HF study was a single-centre, randomized, open-label study comparing diuretic management at the treating physician's discretion as standard of care (SOC) with a nurse-led natriuresis-guided protocol in patients with ADHF. The LAQUAtwin Sodium Meter (HORIBA) was used as point-of-care sensor to measure urine sodium concentration. The primary endpoint was natriuresis after 48 h. Secondary endpoints included safety profile and user-friendliness of both the protocol and the point-of-care sensor. Sixty patients were randomized towards SOC (n = 30) versus protocolized care (n = 30). The mean age was 80 ± 8 years, 25% were women and median N-terminal pro-B-type natriuretic peptide was 4667 (2667-7709) ng/L. Natriuresis after 48 h was significantly higher in the protocolized versus SOC group (820 ± 279 vs. 657 ± 273 mmol; p = 0.027). Pre-defined safety endpoints were similar among both groups. The sensor-based protocol was evaluated as easy to use by the nursing staff, and preferred over urinary collections. CONCLUSION: A nurse-led diuretic titration protocol via a point-of-care urinary sodium sensor was feasible, safe and resulted in an increased natriuresis in ADHF compared to SOC.

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.

Severe coronary artery spasm after administration of a 5-hydroxytryptamine type 1 receptor agonist in a patient with new-onset Graves' disease and myocarditis after SARS-CoV2 vaccination.

BACKGROUND: Coronary artery spasm is a well-known potential side effect of selective 5-hydroxytryptamine type 1 (5HT1) receptor agonists and, therefore, contraindicated in patients with cardiovascular disease. SARS-CoV-2 vaccination has been associated with myocarditis, mainly in young men. CASE SUMMARY: A 55-year-old man with longstanding cluster headache, treated with the 5HT1-agonist Sumatriptan for ten years, received the mRNA-1273 SARS-CoV-2 booster vaccine. Four days later, he developed severe retrosternal pain several minutes after administering Sumatriptan with electrographic ST-elevation and a raised high-sensitivity cardiac troponin-T (hs-cTnT). Coronary angiogram was normal, but a diagnosis of acute myocarditis and hyperthyroidism secondary to Graves' disease was made. DISCUSSION: We present a case of severe coronary artery spasm induced by a 5HT1-agonist secondary to newly diagnosed Graves' disease and myocarditis. The mRNA-1273 SARS-CoV-2 booster vaccine administered four days before admission probably triggered both immunoreactions.

The Potential and Limitations of Mobile Health and Insertable Cardiac Monitors in the Detection of Atrial Fibrillation in Cryptogenic Stroke Patients: Preliminary Results From the REMOTE Trial.

Aim: This paper presents the preliminary results from the ongoing REMOTE trial. It aims to explore the opportunities and hurdles of using insertable cardiac monitors (ICMs) and photoplethysmography-based mobile health (PPG-based mHealth) using a smartphone or smartwatch to detect atrial fibrillation (AF) in cryptogenic stroke and transient ischemic attack (TIA) patients. Methods and Results: Cryptogenic stroke or TIA patients (n = 39) received an ICM to search for AF and were asked to use a blinded PPG-based mHealth application for 6 months simultaneously. They were randomized to smartphone or smartwatch monitoring. In total, 68,748 1-min recordings were performed using PPG-based mHealth. The number of mHealth recordings decreased significantly over time in both smartphone and smartwatch groups (p < 0.001 and p = 0.002, respectively). Insufficient signal quality was more frequently observed in smartwatch (43.3%) compared to smartphone recordings (17.8%, p < 0.001). However, when looking at the labeling of the mHealth recordings on a patient level, there was no significant difference in signal quality between both groups. Moreover, the use of a smartwatch resulted in significantly more 12-h periods (91.4%) that were clinically useful compared to smartphone users (84.8%) as they had at least one recording of sufficient signal quality. Simultaneously, continuous data was collected from the ICMs, resulting in approximately 6,660,000 min of data (i.e., almost a 100-fold increase compared to mHealth). The ICM algorithm detected AF and other cardiac arrhythmias in 10 and 19 patients, respectively. However, these were only confirmed after adjudication by the remote monitoring team in 1 (10%) and 5 (26.3%) patients, respectively. The confirmed AF was also detected by PPG-based mHealth. Conclusion: Based on the preliminary observations, our paper illustrates the potential as well as the limitations of PPG-based mHealth and ICMs to detect AF in cryptogenic stroke and TIA patients in four elements: (i) mHealth was able to detect AF in a patient in which AF was confirmed on the ICM; (ii) Even state-of-the-art ICMs yielded many false-positive AF registrations; (iii) Both mHealth and ICM still require physician revision; and (iv) Blinding of the mHealth results impairs compliance and motivation.

Will Smartphone Applications Replace the Insertable Cardiac Monitor in the Detection of Atrial Fibrillation? The First Comparison in a Case Report of a Cryptogenic Stroke Patient.

Background and Case: This case report exemplifies the clinical application of non-invasive photoplethysmography (PPG)-based rhythm monitoring in the awakening mobile health (mHealth) era to detect symptomatic and asymptomatic paroxysmal atrial fibrillation (AF) in a cryptogenic stroke patient. Despite extensive diagnostic workup, the etiology remains unknown in one out of three ischemic strokes (i.e., cryptogenic stroke). Prolonged cardiac monitoring can reveal asymptomatic atrial fibrillation in up to one-third of this population. This case report describes a cryptogenic stroke patient who received prolonged cardiac monitoring with an insertable cardiac monitor (ICM) as standard of care. In the context of a clinical study, the patient simultaneously monitored his heart rhythm with a PPG-based smartphone application. AF was detected simultaneously on both the ICM and smartphone application after three days of monitoring. Similar AF burden was detected during follow-up (five episodes, median duration of 28 and 34 h on ICM and mHealth, respectively, p = 0.5). The detection prompted the initiation of oral anticoagulation and AF catheter ablation procedure. Conclusion: This is the first report of the cryptogenic stroke patient in whom PPG-based mHealth was able to detect occurrence and burden of the symptomatic and asymptomatic paroxysmal AF episodes with similar precision as ICM. It accentuates the potential role of PPG-based mHealth in prolonged cardiac rhythm monitoring in cryptogenic stroke patients.

Mitral Annular Dynamics in AF Versus Sinus Rhythm: Novel Insights Into the Mechanism of AFMR.

OBJECTIVES: This study aimed to investigate mitral annular dynamics in atrial fibrillation (AF) and after sinus rhythm restoration, and to assess the relationship between annular dynamics and mitral regurgitation (MR). BACKGROUND: AF can be associated with MR that improves after sinus rhythm restoration. Mechanisms underlying this atrial functional MR (AFMR) are ill-understood and generally attributed to left atrial remodeling. METHODS: Fifty-three patients with persistent AF and normal left ventricular ejection fraction were prospectively examined by means of 3-dimensional transesophageal echocardiography before, immediately after, and 6 weeks after electric cardioversion to sinus rhythm. Annular motion was assessed during AF and in sinus rhythm with the use of 3-dimensional analysis software, and the relationship with MR severity was explored. RESULTS: During AF and immediately after sinus rhythm restoration, the mitral annulus behaved relatively adynamically, with an overall change in annular area of 10.3% (95% CI: 8.7%-11.8%) and 12.2% (95% CI: 10.6%-13.8%), respectively. At follow-up, a significant increase in annular dynamics (19.0%; 95% CI: 17.4%-20.6%; P < 0.001) was observed, owing predominantly to an increase in presystolic contraction (P < 0.001). The effective regurgitant orifice area decreased from 0.15 cm2 (0.10-0.23 cm2) during AF to 0.09 cm2 (0.05-0.12 cm2) at follow-up (P < 0.001) in the total cohort, and from 0.27 (0.23-0.33) to 0.16 (0.12-0.29) in the subgroup with effective regurgitant orifice area (EROA) ≥0.20 cm2. The change in presystolic annular motion was the only independent determinant of the decrease in MR severity (P = 0.027), by optimizing annular-leaflet imbalance. Patients with more pronounced blunting of presystolic dynamics had a higher EROA (P < 0.001), because of a lower total-to-closed leaflet area ratio (P < 0.001) at each point in time. This ratio was the strongest independent determinant of AFMR severity (adjusted P = 0.003). CONCLUSIONS: Mitral annular dynamics are impaired in AF, with blunted presystolic narrowing that contributes to AFMR. Sinus rhythm restoration allows gradual recovery of presystolic annular dynamics. Improved annular dynamics decrease AFMR severity by optimizing annular-leaflet imbalance, regardless of LA remodeling.

Outcome and durability of mitral valve annuloplasty in atrial secondary mitral regurgitation.

OBJECTIVES: Atrial secondary mitral regurgitation (ASMR) is a clinically distinct form of Carpentier type I mitral regurgitation (MR), rooted in excessive atrial and mitral annular dilation in the absence of left ventricular dysfunction. Mitral valve annuloplasty (MVA) is expected to provide a more durable solution for ASMR than for ventricular secondary MR (VSMR). Yet data on MR recurrence and outcome after MVA for ASMR are scarce. This study sought to investigate surgical outcomes and repair durability in patients with ASMR, as compared with a contemporary group of patients with VSMR. METHODS: Clinical and echocardiographic data from consecutive patients who underwent MVA to treat ASMR or VSMR in an academic centre were retrospectively analysed. Patient characteristics, operative outcomes, time to recurrence of ≥moderate MR and all-cause mortality were compared between patients with ASMR versus VSMR. RESULTS: Of the 216 patients analysed, 97 had ASMR opposed to 119 with VSMR and subvalvular leaflet tethering. Patients with ASMR were typically female (68.0% vs 33.6% in VSMR, p<0.001), with a history of atrial fibrillation (76.3% vs 33.6% in VSMR, p<0.001), paralleling a larger left atrial size (p<0.033). At a median follow-up of 3.3 (IQR 1.0-7.3) years, recurrence of ≥moderate MR was significantly lower in ASMR versus VSMR (7% vs 25% at 2 years, overall log-rank p=0.001), also when accounting for all-cause death as competing risk (subdistribution HR 0.50 in ASMR, 95% CI 0.29 to 0.88, p=0.016). Moreover, ASMR was associated with better overall survival compared with VSMR (adjusted HR 0.43 95% CI 0.22 to 0.82, p=0.011), independent from baseline European System for Cardiac Operative Risk Evaluation II surgical risk score. CONCLUSION: Prognosis following MVA to treat ASMR is better, compared with VSMR as reflected by lower all-cause mortality and MR recurrence. Early distinction of secondary MR towards underlying ventricular versus atrial disease has important therapeutic implications.

LA Mechanics in Decompensated Heart Failure: Insights From Strain Echocardiography With Invasive Hemodynamics.

OBJECTIVES: The aim of this study was to assess the effect of congestion and decongestive therapy on left atrial (LA) mechanics and to determine the relationship between LA improvement after decongestive therapy and clinical outcome in immediate or chronic heart failure with reduced ejection fraction (HFrEF). BACKGROUND: LA mechanics are affected by volume/pressure overload in decompensated HFrEF. METHODS: A total of 31 patients with HFrEF and immediate heart failure (age 64 ± 15 years, 74% male, left ventricular ejection fraction 20 ± 12%) underwent serial echocardiography during decongestive therapy with simultaneous hemodynamic monitoring. LA function was assessed by strain (rate) imaging. Patients were re-evaluated 6 weeks after discharge and prospectively followed up for the composite endpoint of heart failure readmission and all-cause mortality. RESULTS: LA reservoir function was markedly reduced at baseline and improved with decongestion (peak atrial longitudinal strain from 6.4 ± 2.2% to 8.8 ± 3.0% and strain rate from 0.29 ± 0.11 s-1 to 0.38 ± 0.13 s-1), independent of changes in left ventricular global longitudinal strain, LA end-diastolic volume, and mitral regurgitation severity (p < 0.001). Both measures continued to rise at 6 weeks (up to 13.4 ± 6.1% and 0.50 ± 0.19 s-1, respectively; p < 0.001). LA pump strain rate only increased 6 weeks after discharge (-0.25 ± 0.12 s-1 to -0.55 ± 0.29 s-1; p < 0.010). Changes in LA mechanics correlated with changes in wedge pressure (r = -0.61; p < 0.001). Lower peak atrial longitudinal strain values after decongestion were associated with increased risk for the composite endpoint of heart failure and mortality (p < 0.019). CONCLUSIONS: LA reservoir and booster function, while severely impaired during immediate decompensation, significantly improve during and after decongestive therapy. Poor LA reservoir function after decongestion is associated with worse outcome.

The Detrimental Effect of RA Pacing on LA Function and Clinical Outcome in Cardiac Resynchronization Therapy.

OBJECTIVES: This study assessed the impact of right-atrial (RA) pacing on left-atrial (LA) physiology and clinical outcome. BACKGROUND: Data for the effects of RA pacing on LA synchronicity, function, and structure after cardiac resynchronization therapy (CRT) are scarce. METHODS: The effect of RA pacing on LA function, morphology, and synchronicity was assessed in a prospective imaging cohort of heart failure (HF) patients in sinus rhythm with a guideline-based indication for CRT. Additionally, in a retrospective outcome cohort of consecutive HF patients undergoing CRT implantation, the relationship to RA pacing was assessed using various outcome endpoints. High versus low atrial pacing burden was defined as atrial pacing above or below 50% in both cohorts. RESULTS: A total of 36 patients were included in the imaging cohort (68 ± 11 years of age). Six months after CRT, patients with high RA pacing burden showed less improvement in LA maximum and minimum volumes and total emptying fraction (p < 0.05). Peak atrial longitudinal strain and reservoir and booster strain rates but not conduit strain rate improved after CRT in patients with low RA pacing burden but worsened in patients with high RA pacing burden (p < 0.05 for all). A high RA pacing burden induced significant intra-atrial dyssynchrony (maximum opposing wall delay: 44 ± 13 ms vs. 97 ± 17 ms, respectively; p = 0.022). A total of 569 patients were included in the outcome cohort. After covariate adjustments were made, a high RA pacing burden was associated with reduced LV reverse remodeling (ß = 8.738; 95% confidence interval [CI]: 3.101 to 14.374; p = 0.002) and new-onset or recurrent atrial fibrillation (41% vs. 22%, respectively, at a median of 31 months [range 22 to 44 months follow-up]; p < 0.001). There were no differences in time to first HF hospitalization or all-cause mortality (p = 0.185) after covariate adjustment. However, in a recurrent event analysis, HF readmissions were more common in patients exposed to a high RA pacing burden (p = 0.003). CONCLUSIONS: RA pacing in CRT patients negatively influences LA morphology, function, and synchronicity, which is associated with worse clinical outcome, including diminished LV reverse remodeling, increased risk for new-onset or recurrent AF and heart failure readmission. Strategies reducing RA pacing burden may be warranted.

Atrial Functional Mitral Regurgitation: JACC Review Topic of the Week.

Unlike secondary mitral regurgitation (MR) in the setting of left ventricular (LV) disease, the occurrence of functional MR in atrial fibrillation (AF) and/or heart failure with preserved ejection fraction (HFpEF) has remained largely unspoken. LV size and systolic function are typically normal, whereas isolated mitral annular dilation and inadequate leaflet adaptation are considered mechanistic culprits. Moreover, the role of left atrial and annular dynamics in provoking MR is often underappreciated. Because of this peculiar pathophysiology, atrial functional MR benefits from a different approach compared with secondary MR. Although both AF and HFpEF-two closely related disease epidemics of the 21st century-are held responsible, current guidelines do not emphasize the need to differentiate atrial functional MR from (ventricular) secondary MR. This review summarizes the prevalence and prognostic importance of atrial functional MR, providing mechanistic insights compared with those of secondary MR and suggesting potential therapeutic targets.

Effect of Cardiac Resynchronization Therapy on Exercise-Induced Pulmonary Hypertension and Right Ventricular-Arterial Coupling.

Background Acute and chronic effects of cardiac resynchronization therapy (CRT) on pulmonary pressures, right ventricular function, and ventricular-vascular coupling during exercise are insufficiently understood. Yet, these factors are strongly associated with functional status and outcome. Methods and Results Heart failure patients with reduced ejection fraction indicated for CRT were prospectively included to undergo exercise echocardiography simultaneously with cardiopulmonary exercise testing before (pre_CRT), 1 day after (post_CRT), and 6 months (post6_CRT) after CRT implant. Right ventricular-arterial coupling was assessed by the tricuspid annular plane systolic excursion (TAPSE)/systolic pulmonary artery pressure (SPAP) ratio. A total of 31 heart failure patients with reduced ejection fraction (age=66±13 years) were prospectively included. CRT resulted in an immediate reduction in rest SPAP (pre_CRT=32±16 versus post_CRT=23±16 mm Hg; P=0.006) and rest effective regurgitant orifice (pre_CRT=0.32±0.1 versus post_CRT=0.18±0.2; P=0.001) without changes in exercise mitral regurgitation or exercise SPAP indexed for cardiac output. Six months after CRT, in parallel with left ventricular reverse remodeling and a reduction in exercise mitral regurgitation and exercise E/e' ratio, the exercise SPAP/cardiac output significantly improved (post_CRT=5.6±3.1 versus post6_CRT=4.3±2.9 mm Hg·L-1·min-1; P=0.039), which was also illustrated by a reduced slope of ΔSPAP/Δcardiac output (post_CRT=5.2±3.7 versus post6_CRT=2.9±2.7 mm Hg·L-1·min-1; P=0.002). CRT did not result in an acute or chronic effect on TAPSE or TAPSE/SPAP ratio at rest. However, exercise revealed the presence of right ventricular-arterial uncoupling which was not affected by an acute CRT effect ( P=0.396) but only improved by a chronic CRT effect ( P<0.001; TAPSE/SPAP ratio: pre_CRT= 0.39±0.6 mm/mm Hg; post_CRT=0.42±0.5 mm/mm Hg; post6_CRT =0.84±0.12 mm/mm Hg). Of all exercise echocardiography variables, the TAPSE/SPAP ratio demonstrated the strongest correlation with Vo2 peak ( r=0.475), VE/Vco2 ( r=-0.585), and workload ( r=0.476) during cardiopulmonary exercise testing ( P<0.05 all). Multivariate predictors affecting exercise ventricular-arterial coupling after CRT included metrics of residual exercise mitral regurgitation and systolic and diastolic left ventricular function. Conclusions Chronic CRT beneficially influences pulmonary pressures and right ventricular-arterial coupling during exercise, which strongly relates to functional status. These findings are mechanistically linked to reverse remodeling with improved interventricular dependence and reduction in exercise mitral regurgitation.

One-year clinical and computed tomography follow-up after implantation of bioresorbable vascular scaffolds in patients with coronary chronic total occlusions.

OBJECTIVES: To assess the safety and efficacy of everolimus-eluting bioresorbable scaffolds (BRS) in the treatment of chronic total occlusions (CTO) using noninvasive multislice computed tomography (MSCT) angiography at one-year follow-up. BACKGROUND: Current evidence regarding the safety and efficacy of BRS for the percutaneous treatment of CTO is limited. METHODS: Between September 2013 and January 2016, patients who received one or more ABSORB BRSs were included at three centers. MSCT (including quantitative analysis) and clinical follow-up were performed at one year. RESULTS: Forty-one CTO patients were included. Mean age was 60 ± 11 years and the majority was male (83%). Average Japanese CTO (J-CTO) score was 0.9 ± 0.9. Seventy-one BRS were implanted in total with, on average, 1.7 ± 0.8 scaffolds/patient, and a total length of 43 ± 20 mm and diameter of 3.1 ± 0.4 mm. One noncardiac death took place. MSCT angiography was performed in 34 (83%) patients: all scaffolds were patent, except in one patient, in whom a patent target vessel was present on subsequent diagnostic angiography. MSCT quality was sufficient for quantitative analyses in 27 patients (46 scaffolds): median reference versus scaffold minimal lumen diameter and minimal lumen area were measured, and showed a small difference of 0.1 mm (-0.2-0.4) (lumen diameter stenosis = 3.0%) and 0.5 mm2 (-1.0-2.0) (lumen area stenosis = 4.2%). CONCLUSIONS: The low number of events and high patency rate at 1 year are encouraging the further use of the ABSORB scaffold for CTOs with low J-CTO score. Noninvasive MSCT angiography is a valid tool to assess scaffold patency, although its image resolution limits the use for quantitative measurements.

Loop diuretic down-titration in stable chronic heart failure is often achievable, especially when urinary chloride concentration is low.

BACKGROUND: This study investigates spot urinary chloride concentration in euvolemic chronic heart failure (CHF) patients. METHODS: This prospective cohort study included 50 ambulatory CHF patients on maintenance loop diuretics without recent hospital admission, clinical signs of volume overload, or adjustment in neurohumoral blocker or diuretic therapy. Spot urinary samples were collected immediately after loop diuretic intake. Subsequently, loop diuretic dose was reduced with 50% or stopped if ≤40 mg furosemide equivalents. Successful down-titration was defined as persistent dose reduction after 7 d without body weight increase >1.5 kg. RESULTS: Urinary chloride concentration was 3045 ± 1271 mg/L overall. Patients with higher versus lower urinary chloride concentrations took the same dose of loop diuretics [40 mg (20-40 mg) furosemide equivalents; p value = .509] and had similar plasma NT-proBNP levels [1179 ng/L (311-2195 ng/L) versus 900 ng/L (255-1622 ng/L), respectively; p value = .461]. Down-titration was successful in 72% versus 76%, respectively (p value = 1.000). At 30 d, loop diuretic dose remained reduced in 59% versus 76% of patients, respectively (p value = .238). The proportion of patients free from diuretic therapy was 45% versus 62% in the high versus low chloride concentration group (p value = .265). CONCLUSIONS: Loop diuretic down-titration was successful in 3 out of 4 euvolemic CHF patients, irrespectively of urinary chloride concentration on spot samples collected after diuretic intake.

Effective Orifice Area during Exercise in Bileaflet Mechanical Valve Prostheses.

BACKGROUND: The aims of this study were to investigate the evolution of the transprosthetic pressure gradient and effective orifice area (EOA) during dynamic bicycle exercise in bileaflet mechanical heart valves and to explore the relationship with exercise capacity. METHODS: Patients with bileaflet aortic valve replacement (n = 23) and mitral valve replacement (MVR; n = 16) prospectively underwent symptom-limited supine bicycle exercise testing with Doppler echocardiography and respiratory gas analysis. Transprosthetic flow rate, peak and mean transprosthetic gradient, EOA, and systolic pulmonary artery pressure were assessed at different stages of exercise. RESULTS: EOA at rest, midexercise, and peak exercise was 1.66 ± 0.23, 1.56 ± 0.30, and 1.61 ± 0.28 cm2, respectively (P = .004), in aortic valve replacement patients and 1.40 ± 0.21, 1.46 ± 0.27, and 1.48 ± 0.25 cm2, respectively (P = .160), in MVR patients. During exercise, the mean transprosthetic gradient and the square of transprosthetic flow rate were strongly correlated (r = 0.65 [P < .001] and r = 0.84 [P < .001] for aortic valve replacement and MVR, respectively), conforming to fundamental hydraulic principles for fixed orifices. Indexed EOA at rest was correlated with exercise capacity in MVR patients only (Spearman ρ = 0.68, P = .004). In the latter group, systolic pulmonary artery pressures during exercise were strongly correlated with the peak transmitral gradient (ρ = 0.72, P < .001). CONCLUSIONS: In bileaflet mechanical valve prostheses, there is no clinically relevant increase in EOA during dynamic exercise. Transprosthetic gradients during exercise closely adhere to the fundamental pressure-flow relationship. Indexed EOA at rest is a strong predictor of exercise capacity in MVR patients. This should be taken into account in therapeutic decision making and prosthesis selection in young and dynamic patients.

Global myocardial oedema in advanced decompensated heart failure.

AIMS: To use cardiac magnetic resonance (CMR) imaging with quantitative T2 mapping as surrogate for myocardial water content in patients with advanced decompensated heart failure (ADHF), compare these values with T2-values observed in chronic heart failure, and evaluate the change with decongestive therapy. METHODS AND RESULTS: Volumetric CMR measurements and quantitative T2 mapping were performed in 18 consecutive ADHF patients with clinical signs of volume overload. Eleven patients with stable heart failure were used as controls. Vasodilator therapy and diuretics were administered to achieve a pulmonary arterial wedge pressure (PAWP) of <18 mmHg and central venous pressure (CVP) of <12 mmHg, after which CMR was repeated. ADHF patients (62 ± 12 years; 89% male; left ventricular ejection fraction 23 ± 8%) presented with low cardiac index (2.08 ± 0.59 L/min/m2), high PAWP (25 ± 7 mmHg), and high CVP (14 ± 5 mmHg). After decongestion, the patients had a significant increase in cardiac index (+0.41 ± 0.53 L/min/m2; P = 0.005) and decreases in both PAWP (-9 ± 6 mmHg; P < 0.001) and CVP (-6 ± 5 mmHg; P < 0.001). At baseline, global left ventricular T2-values were higher in ADHF patients compared with controls (59.5 ± 4.6 vs. 54.7 ± 2.2 ms, respectively; P = 0.001). After decongestion, T2-values fell significantly to 55.9 ± 5.1 ms (P = 0.001), comparable with controls (P = 0.580). In contrast, psoas muscle T2-values were similar at baseline (38.6 ± 4.4 ms) vs. after decongestion (37.8 ± 4.8 ms; P = 0.397). Each 1 ms decrease in global left ventricular T2-value during decongestion was associated with a 1.14 ± 0.40 mmHg decrease in PAWP (P = 0.013), after correction for age and gender. CONCLUSION: Patients presenting with ADHF and volume overload have increased global left ventricular-but not psoas muscle-T2-values, which decrease with successful decongestion. Relief of myocardial oedema correlates with haemodynamic unloading.

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.

Comparison of left ventricular torsion and strain with biventricular pacing in patients with underlying right bundle branch block versus those with left bundle branch block.

The benefits of biventricular pacing in patients with cardiac resynchronization therapy (CRT) remain poorly understood in those with right bundle branch block (RBBB). The aim of this study was to examine the differences in several speckle tracking-derived parameters, including left ventricular torsion and longitudinal strain with CRT on and off for patients with underlying left bundle branch block (LBBB) and RBBB. Twelve patients with CRT and RBBB were compared with a similar group of patients with underlying LBBB who were sent for evaluation and atrioventricular optimization. Echocardiographic images were acquired with biventricular pacing on and off. The 2 groups had similar baseline characteristics, including age, the ejection fraction, and QRS duration. During intrinsic conduction (CRT off), patients with LBBB had lower torsion angles than those with RBBB (2.3 ± 1.0° in those with LBBB vs 6.3 ± 1.0° in those with RBBB, p = 0.03) but trended toward improvements in torsional parameters, including torsional angle and peak untwisting velocity with CRT on, whereas these parameters worsened in patients with RBBB. Compared with CRT off, analyses of septal and lateral strain curves showed significant improvements in septal strain during 100% and 200% of systole with CRT on in patients with LBBB, whereas biventricular pacing resulted in a trend toward worsening of septal strain in patients with RBBB. Negligible changes were noted in lateral strain values. In conclusion, CRT favorably improves regional mechanics in patients with LBBB primarily involving the ventricular septum, with a negligible positive impact on cardiac function in patients with underlying RBBB.

Pulmonary vascular response to exercise in symptomatic heart failure with reduced ejection fraction and pulmonary hypertension.

AIMS: To study pulmonary vascular response patterns to exercise in heart failure with reduced ejection fraction (HFrEF) and pulmonary hypertension (PH). METHODS AND RESULTS: In this prospective single-centre cohort study, consecutive symptomatic HFrEF patients (n = 40) with mean pulmonary arterial pressure (MPAP) ≥25 mmHg, pulmonary artery wedge pressure (PAWP) >15 mmHg, and cardiac index <2.5 L/min.m(2) , received protocol-driven titrated sodium nitroprusside (SNP) and diuretics to reach mean arterial blood pressure 65-75 mmHg and PAWP ≤15 mmHg. Patients performed symptom-limited supine bicycle testing under continued SNP administration. Afterwards, SNP was gradually withdrawn, renin-angiotensin system blockers uptitrated, and hydralazine added to maintain haemodynamic targets. Subsequently, bicycle testing was repeated. Patients presented with pulmonary vascular resistance (PVR) = 3.8 ± 1.4 Wood Units at rest, decreasing to 2.9 ± 0.9 Wood Units after decongestion, with PH was completely reversed (MPAP <25 mmHg) in 22%. From rest to maximal exercise, the cardiac index did not change significantly (P = 0.334 under SNP; P-value = 0.552 under oral therapy). A dynamic exercise-induced PVR increase >3.5 Wood Units was noted in 19 patients (48%) under oral therapy vs. five (13%) under SNP. Such exercise-induced PVR increase was associated with a 33% relative decrease in right ventricular stroke work index (P = 0.037). CONCLUSIONS: Even after thorough decongestion and under continuous afterload reduction, PH secondary to HFrEF is completely reversible in only a minority of patients. Others demonstrate an exercise-induced PVR increase, associated with impaired right ventricular stroke work, which might be ameliorated by nitric oxide donor support.

Mitral valve area during exercise after restrictive mitral valve annuloplasty: importance of diastolic anterior leaflet tethering.

BACKGROUND: Restrictive mitral valve annuloplasty (RMA) for secondary mitral regurgitation might cause functional mitral stenosis, yet its clinical impact and underlying pathophysiological mechanisms remain debated. OBJECTIVES: The purpose of our study was to assess the hemodynamic and clinical impact of effective orifice area (EOA) after RMA and its relationship with diastolic anterior leaflet (AL) tethering at rest and during exercise. METHODS: Consecutive RMA patients (n = 39) underwent a symptom-limited supine bicycle exercise test with Doppler echocardiography and respiratory gas analysis. EOA, transmitral flow rate, mean transmitral gradient, and systolic pulmonary arterial pressure were assessed at different stages of exercise. AL opening angles were measured at rest and peak exercise. Mortality and heart failure readmission data were collected for at least 20 months after surgery. RESULTS: EOA and AL opening angle were 1.5 ± 0.4 cm(2) and 68 ± 10°, respectively, at rest (r = 0.4; p = 0.014). EOA increased significantly to 2.0 ± 0.5 cm(2) at peak exercise (p < 0.001), showing an improved correlation with AL opening angle (r = 0.6; p < 0.001). Indexed EOA (EOAi) at peak exercise was an independent predictor of exercise capacity (maximal oxygen uptake, p = 0.004) and was independently associated with freedom from all-cause mortality or hospital admission for heart failure (p = 0.034). Patients with exercise EOAi <0.9 cm(2)/m(2) (n = 14) compared with ≥0.9 cm(2)/m(2) (n = 25) had a significantly worse outcome (p = 0.048). In multivariate analysis, AL opening angle at peak exercise (p = 0.037) was the strongest predictor of exercise EOAi. CONCLUSIONS: In RMA patients, EOA increases during exercise despite fixed annular size. Diastolic AL tethering plays a key role in this dynamic process, with increasing AL opening during exercise being associated with higher exercise EOA. EOAi at peak exercise is a strong and independent predictor of exercise capacity and is associated with clinical outcome. Our findings stress the importance of maximizing AL opening by targeting the subvalvular apparatus in future repair algorithms for secondary mitral regurgitation.