Viability and Outcomes With Revascularization or Medical Therapy in Ischemic Ventricular Dysfunction: A Prespecified Secondary Analysis of the REVIVED-BCIS2 Trial.

Importance: In the Revascularization for Ischemic Ventricular Dysfunction (REVIVED-BCIS2) trial, percutaneous coronary intervention (PCI) did not improve outcomes for patients with ischemic left ventricular dysfunction. Whether myocardial viability testing had prognostic utility for these patients or identified a subpopulation who may benefit from PCI remained unclear. Objective: To determine the effect of the extent of viable and nonviable myocardium on the effectiveness of PCI, prognosis, and improvement in left ventricular function. Design, Setting, and Participants: Prospective open-label randomized clinical trial recruiting between August 28, 2013, and March 19, 2020, with a median follow-up of 3.4 years (IQR, 2.3-5.0 years). A total of 40 secondary and tertiary care centers in the United Kingdom were included. Of 700 randomly assigned patients, 610 with left ventricular ejection fraction less than or equal to 35%, extensive coronary artery disease, and evidence of viability in at least 4 myocardial segments that were dysfunctional at rest and who underwent blinded core laboratory viability characterization were included. Data analysis was conducted from March 31, 2022, to May 1, 2023. Intervention: Percutaneous coronary intervention in addition to optimal medical therapy. Main Outcomes and Measures: Blinded core laboratory analysis was performed of cardiac magnetic resonance imaging scans and dobutamine stress echocardiograms to quantify the extent of viable and nonviable myocardium, expressed as an absolute percentage of left ventricular mass. The primary outcome of this subgroup analysis was the composite of all-cause death or hospitalization for heart failure. Secondary outcomes were all-cause death, cardiovascular death, hospitalization for heart failure, and improved left ventricular function at 6 months. Results: The mean (SD) age of the participants was 69.3 (9.0) years. In the PCI group, 258 (87%) were male, and in the optimal medical therapy group, 277 (88%) were male. The primary outcome occurred in 107 of 295 participants assigned to PCI and 114 of 315 participants assigned to optimal medical therapy alone. There was no interaction between the extent of viable or nonviable myocardium and the effect of PCI on the primary or any secondary outcome. Across the study population, the extent of viable myocardium was not associated with the primary outcome (hazard ratio per 10% increase, 0.98; 95% CI, 0.93-1.04) or any secondary outcome. The extent of nonviable myocardium was associated with the primary outcome (hazard ratio, 1.07; 95% CI, 1.00-1.15), all-cause death, cardiovascular death, and improvement in left ventricular function. Conclusions and Relevance: This study found that viability testing does not identify patients with ischemic cardiomyopathy who benefit from PCI. The extent of nonviable myocardium, but not the extent of viable myocardium, is associated with event-free survival and likelihood of improvement of left ventricular function. Trial Registration: ClinicalTrials.gov Identifier: NCT01920048.

Cardioprotective medication in Duchenne muscular dystrophy: a single-centre cohort study.

Background: Duchenne muscular dystrophy (DMD) is a neuromuscular disorder characterised by progressive muscle wasting impacting mobility, ventilation and cardiac function. Associated neuromuscular cardiomyopathy remains a major cause of morbidity and mortality. We investigated the effects of cardioprotective medications [angiotensin-converting enzyme inhibitors (ACE-I), beta-blockers] on clinical outcomes in DMD patients. Methods: This was a retrospective cohort study (reference: 2021/12469) of DMD patients at a tertiary centre between 1993-2021 screening the electronic records for demographics, comorbidities, medication, disease specific features, echocardiography, hospitalisations, and ventilator use. Results: A total of 68 patients were identified aged 27.4 (6.6) years, of which 52 were still alive. There was a difference in body mass index (BMI) between survivors and deceased patients [23.8 (5.9) vs. 19.9 (3.8) kg/m2, P=0.03]. Home mechanical ventilation (HMV) was required in 90% of patients, 85% had DMD associated cardiomyopathy. About 2/3 of all hospitalisations during the observation period were secondary to cardiopulmonary causes. The left ventricular ejection fraction (LVEF) at initial presentation was 44.8% (10.6%) and declined by 3.3% [95% confidence interval (CI): 0.4% to -7.0%] over the follow up period (P=0.002). A total of 61 patients were established on ACE-I for 75.9% (35.1%), and 62 were on beta-blockers for 73.6% (33.5%) of the follow up period. There was a significant LVEF decline in those taking ACE-I for limited periods compared to those permanently on ACE-I (P=0.002); a similar effect was recorded with beta-blockers (P=0.02). Conclusions: Long-term use of ACE-I and beta-blockers is associated with a reduced decline in LVEF in patients with DMD and may be protective of adverse cardiovascular ill health.

Cardiac care of children with dystrophinopathy and females carrying DMD-gene variations.

OBJECTIVE: We provide succinct, evidence-based and/or consensus-based best practice guidance for the cardiac care of children living with Duchenne muscular dystrophy (DMD) as well as recommendations for screening and management of female carriers of mutations in the DMD-gene. METHODS: Initiated by an expert working group of UK-based cardiologists, neuromuscular clinicians and DMD-patient representatives, draft guidelines were created based on published evidence, current practice and expert opinion. After wider consultation with UK-cardiologists, consensus was reached on these best-practice recommendations for cardiac care in DMD. RESULTS: The resulting recommendations are presented in the form of a succinct care pathway flow chart with brief justification. The guidance signposts evidence on which they are based and acknowledges where there have been differences in opinion. Guidelines for cardiac care of patients with more advanced cardiac dystrophinopathy at any age have also been considered, based on the previous published work of Quinlivan et al and are presented here in a similar format. The recommendations have been endorsed by the British Cardiovascular Society. CONCLUSION: These guidelines provide succinct, reasoned recommendations for all those managing paediatric patients with early or advanced stages of cardiomyopathy as well as females with cardiac dystrophinopathy. The hope is that this will result in more uniform delivery of high standards of care for children with cardiac dystrophinopathy, so improving heart health into adulthood through timely earlier interventions across the UK.

The Doppler paradox.

Obstructive prosthetic valve thrombosis (PVT) is a rare but severe complication that usually occurs in the presence of suboptimal anticoagulation. Although fluoroscopy is commonly used to detect abnormal leaflet motion as a surrogate marker for PVT, its inability to directly visualize adjacent tissue and valve physiology leaves it susceptible to miss clinically important PVT. In this manuscript, we report the case of a 54-year-old woman with a mechanical mitral valve who was admitted to our institute with exertional dyspnea. Although valve fluoroscopy was normal, subsequent 3D echocardiography and ECG-gated multiphase computed tomography confirmed the presence of PVT that was subsequently treated successfully with surgical replacement. Our case demonstrates the utility of multimodality imaging in establishing PVT in patients with abnormal prosthetic valve physiology and progressive symptoms.

Clinical utility of speckle-tracking echocardiography in cardiac resynchronisation therapy.

Cardiac resynchronisation therapy (CRT) can profoundly improve outcome in selected patients with heart failure; however, response is difficult to predict and can be absent in up to one in three patients. There has been a substantial amount of interest in the echocardiographic assessment of left ventricular dyssynchrony, with the ultimate aim of reliably identifying patients who will respond to CRT. The measurement of myocardial deformation (strain) has conventionally been assessed using tissue Doppler imaging (TDI), which is limited by its angle dependence and ability to measure in a single plane. Two-dimensional speckle-tracking echocardiography is a technique that provides measurements of strain in three planes, by tracking patterns of ultrasound interference ('speckles') in the myocardial wall throughout the cardiac cycle. Since its initial use over 15 years ago, it has emerged as a tool that provides more robust, reproducible and sensitive markers of dyssynchrony than TDI. This article reviews the use of two-dimensional and three-dimensional speckle-tracking echocardiography in the assessment of dyssynchrony, including the identification of echocardiographic parameters that may hold predictive potential for the response to CRT. It also reviews the application of these techniques in guiding optimal LV lead placement pre-implant, with promising results in clinical improvement post-CRT.

Factors influencing left ventricular outflow tract obstruction following a mitral valve-in-valve or valve-in-ring procedure, part 1.

OBJECTIVES: To determine the factors influencing left ventricular outflow tract (LVOT) area reduction after a mitral valve-in-valve (VIV) or a valve-in-ring (VIR) procedure. BACKGROUND: Transcatheter heart valves (THVs) are increasingly used in performing a VIV or a VIR procedure in high-risk patients. Although less invasive, a potential complication is LVOT obstruction. However, the factors predisposing to LVOT obstruction are ill defined. METHODS AND RESULTS: To understand the effects of the various factors, the study was carried out in three parts: To understand the effect of VIV and VIR on reduction in LVOT area with special attention to different surgical heart valve (SHV) orientations and depth of THV implant. This was carried out in porcine and cadaver hearts. To quantify aorto-mitral-annular (AMA) angle in 20 patients with or without mitral disease and to derive a static computational model to predict LVOT obstruction. To study the effect of SHV design on LVOT obstruction after VIV. This was carried out as a bench test. LVOT area reduction was similar after VIV irrespective of orientation of the mitral SHV implantation as it pinned open the SHV leaflets. Similar effect was seen after VIR. The degree of LVOT obstruction was partly determined by AMAangle and was inversely proportional. SHV design, ring design, and depth of SPAIEN XT implantation also had effect on LVOT obstruction. CONCLUSIONS: A possibility of LVOT obstruction should be considered when performing a VIV and VIR procedure. Type of SHV, flexible ring, less obtuse AMA angle, and depth of SAPIEN XT implant can influence the risk.

Interinstitutional measurements of left ventricular volumes, speckle-tracking strain, and dyssynchrony using three-dimensional echocardiography.

BACKGROUND: Three-dimensional echocardiographic (3DE) analysis provides better measurements of left ventricular (LV) volumes, ejection fraction, myocardial deformation, and dyssynchrony. Many studies have shown that this technique has high intrainstitutional reproducibility. However, interinstitutional reproducibility is low, limiting its adoption. The aim of this study was to determine if standardization of training could reduce the interinstitutional variability in 3DE data analysis. METHODS: In total, 50 full-volume, transthoracic 3DE data sets of the left ventricle were analyzed by two readers. Measurements obtained included LV volumes, ejection fraction, global longitudinal strain, and two dyssynchrony indices. The cases represented a wide spectrum of ejection fraction. After initial analysis of 21 studies, readers formally met to standardize their analytic approach on six additional cases. Five months after the intervention, 23 new cases were analyzed. Paired t tests were performed to identify systematic institutional differences in measurements. Interinstitutional variability was quantified using intraclass correlation coefficients and variability. RESULTS: Before the intervention, there was a systematic bias in LV volumes, which was eliminated after intervention. Intraclass correlation coefficients showed that the intervention improved agreement in measurements of LV volumes, strain, and dyssynchrony between the two centers and decreased variability. CONCLUSIONS: A simple intervention to standardize analysis can reduce interinstitutional variability of measurements obtained from 3DE analysis. This intervention is needed before the use of 3DE measurement in multicenter trials and to increase the reproducibility of such measurements in routine clinical practice.

Cardiac magnetic resonance-derived anatomy, scar, and dyssynchrony fused with fluoroscopy to guide LV lead placement in cardiac resynchronization therapy: a comparison with acute haemodynamic measures and echocardiographic reverse remodelling.

AIMS: Left ventricular (LV) lead positioning for cardiac resynchronization therapy (CRT) is largely empirical and operator-dependent. Our aim was to determine whether cardiac magnetic resonance (CMR)-guided CRT may improve the acute and the chronic response. METHODS AND RESULTS: CMR-derived anatomical models and dyssynchrony maps were created for 20 patients. The CMR targets (three latest activated segments with <50% scar) were overlaid on to live fluoroscopy. Acute haemodynamic response (AHR) to LV pacing was assessed using an intra-ventricular pressure wire. Chronic CRT response (end-systolic volume reduction ≥15%) was assessed 6 months post-implantation. All patients underwent successful CMR-guided LV lead placement. A CMR target segment was paced in 75% of patients. The mean change in LVdP/dtmax for the CMR target was +14.2 ± 12.5 vs. +18.7 ± 11.9% for the best AHR in any segment and +12.0 ± 13.8% for the segment based on coronary sinus (CS) venography. Using CMR guidance, the acute responder rate was 60 vs. 50% on the basis of venography. At 6 months 60% of patients were echocardiographic responders. Of the echocardiographic responders, 92% were successfully paced in a CMR target segment compared with only 50% of non-responders (P = 0.04). CONCLUSION: CMR guidance compared well when validated against the AHR. Lead placement was possible in the CMR target region in most patients with an AHR comparable with the best achieved in any CS branch. The chronic response was significantly better in patients paced in a CMR target segment. These results suggest that CMR guidance may represent a clinically useful tool for CRT.

Adverse response to cardiac resynchronisation therapy in patients with septal scar on cardiac MRI preventing a septal right ventricular lead position.

PURPOSE: Myocardial scar is an adverse factor when considering which patients are likely to respond to cardiac resynchronisation therapy (CRT). We hypothesized that septal scarring on magnetic resonance imaging (MRI) may be associated with a poor outcome from CRT, which may relate to the inability to place the right ventricular (RV) lead in the septum. METHODS: Fifty patients (ejection fractions, 25 ± 8%; 45 men, 62.8 ± 14 years; 26 dilated cardiomyopathy; and 24 ischaemic cardiomyopathy (ICM)) receiving CRT underwent delayed enhancement cardiac MRI to assess location and burden of myocardial scar. Acute hemodynamic response (AHR) was evaluated at implant with a pressure wire in the left ventricular (LV) cavity. LV remodelling was determined by reduction in LV end-systolic volume at 6 months. RESULTS: The presence of ICM with septal scar was associated with a poor acute and chronic response to CRT. This was predominantly due to a worse response in patients with septal scar. Patients without septal scar had a better AHR with a 26.7 ± 28.9% rise in LV dP/dt (max) from baseline vs. -2.8 ± 14.5% for patients with septal scar (P = 0.01) with Biventricular (BIV) pacing. A greater proportion remodelled (56% vs. 20% (P = 0.02)). Furthermore, only 33% of patients with septal scar had an RV septal lead compared with 66% with no septal scar (P = 0.03). CONCLUSIONS: The presence of septal scar was associated with a poor acute and chronic response to CRT. This may relate to the inability to achieve a RV septal lead placement.

Invasive acute hemodynamic response to guide left ventricular lead implantation predicts chronic remodeling in patients undergoing cardiac resynchronization therapy.

OBJECTIVES: We evaluated the relationship between acute hemodynamic response (AHR) and reverse remodeling (RR) in cardiac resynchronization therapy (CRT). BACKGROUND: CRT reduces mortality and morbidity in heart failure patients; however, up to 30% of patients do not derive symptomatic benefit. Higher proportions do not remodel. Multicenter trials have shown echocardiographic techniques are poor at improving response rates. We hypothesized the degree of AHR at implant can predict which patients remodel. METHODS: Thirty-three patients undergoing CRT (21 dilated and 12 ischemic cardiomyopathy) were studied. Left ventricular (LV) volumes were assessed before and after CRT. The AHR (maximum rate of left ventricular pressure [LV-dP/dt(max)]) was assessed at implant with a pressure wire in the LV cavity. Largest percentage rise in LV-dP/dt(max) from baseline (atrial antibradycardia pacing or right ventricular pacing with atrial fibrillation) to dual-chamber pacing (DDD)-LV was used to determine optimal coronary sinus LV lead position. Reverse remodeling was defined as reduction in LV end systolic volume ≥15% at 6 months. RESULTS: The LV-dP/dt(max) increased significantly from baseline (801 ± 194 mm Hg/s to 924 ± 203 mm Hg/s, p < 0.001) with DDD-LV pacing for the optimal LV lead position. The LV end systolic volume decreased from 186 ± 68 ml to 157 ± 68 ml (p < 0.001). Eighteen (56%) patients exhibited RR. There was a significant relationship between percentage rise in LV-dP/dt(max) and RR for DDD-LV pacing (p < 0.001). A similar relationship for AHR and RR in dilated cardiomyopathy and ischemic cardiomyopathy (p = 0.01 and p = 0.006) was seen. CONCLUSIONS: Acute hemodynamic response to LV pacing is useful for predicting which patients are likely to remodel in response to CRT both for dilated cardiomyopathy and ischemic cardiomyopathy. Using AHR has the potential to guide LV lead positioning and improve response rates.

The potential impact of contemporary transthoracic echocardiography on the management of patients with native valve endocarditis: a comparison with transesophageal echocardiography.

BACKGROUND: Between 1987 and 1994, several studies demostrated transthoracic echocardiography (TTE) to be less sensitive than transesophageal echocardiography (TEE) in detecting native valve endocarditis. Recent technologic advances, especially the introduction of harmonic imaging and digital processing and storage, have improved TTE image quality. The aim of this study was to determine the diagnostic accuracy of contemporary TTE. METHODS: Between 2003 and 2007, 75 patients underwent both TTE and TEE for clinically suspected infective endocarditis. The diagnostic accuracy of TTE was assessed using transesophageal echocardiography as the gold standard for diagnosis of endocarditis. RESULTS: Of the 75 patients in this study, 33 were found to be positive by TEE. The sensitivity for detection of infective endocarditis by TTE was 81.8%. It provided good image quality in 81.5% of cases; in these patients sensitivity was even greater (89.3%). CONCLUSION: Contemporary TTE has improved the diagnostic accuracy of infective endocarditis by ameliorating image quality; it provides an accurate assessment of endocarditis and may reduce the need for TEE.