Clinical course of arrhythmogenic right ventricular cardiomyopathy with end-stage heart failure and outcome after heart transplantation

BackgroundFew data exist on the characteristics and outcomes of patients with arrhythmogenic right ventricular cardiomyopathy and advanced heart failure who undergo heart transplantation.AimTo explore the pretransplant course and outcomes of patients with arrhythmogenic right ventricular cardiomyopathy after heart transplantation.MethodsThis observational retrospective monocentric study included all consecutive patients with arrhythmogenic right ventricular cardiomyopathy who underwent heart transplantation during a 13-year period (2006–2019) at Pitié-Salpêtrière University Hospital (Paris).ResultsA total of 23 patients with arrhythmogenic right ventricular cardiomyopathy underwent heart transplantation between 2006 and 2019. The median time from diagnosis to heart transplantation was 9 years, and the median age at transplantation was 50 years. At diagnosis, half of the patients had left ventricular dysfunction, 59% had extensive T-wave inversion and 43% had a history of sustained ventricular tachycardia. Only five patients were involved in intensive sport activity. Indications for heart transplantation were end-stage biventricular dysfunction in 13 patients, end-stage right ventricular heart failure in seven and electrical storm in three. Only three patients had pulmonary hypertension, and half of the patients had atrial arrhythmias. The survival rate 1 year after heart transplantation was 74% (95% confidence interval 53–88%). Eight patients experienced primary graft dysfunction needing extracorporeal membrane oxygenation.ConclusionsPatients with arrhythmogenic right ventricular cardiomyopathy who eventually needed heart transplantation mostly exhibited extended disease with biventricular dysfunction at diagnosis. Intensive sport activity did not seem to be a major determinant. Advanced heart failure usually occurred late in the course of the disease. Primary graft dysfunction after heart transplantation was frequent, and should be anticipated. Additional data are needed to identify the optimal timing for heart transplantation and predictors of end-stage heart failure in patients with arrhythmogenic right ventricular cardiomyopathy.     

Arrhythmia-Induced Cardiomyopathy: JACC State-of-the-Art Review

Arrhythmias coexist in patients with heart failure (HF) and left ventricular (LV) dysfunction. Tachycardias, atrial fibrillation, and premature ventricular contractions are known to trigger a reversible dilated cardiomyopathy referred as arrhythmia-induced cardiomyopathy (AiCM). It remains unclear why some patients are more prone to develop AiCM despite similar arrhythmia burdens. The challenge is to determine whether arrhythmias are fully, partially, or at all responsible for an observed LV dysfunction. AiCM should be suspected in patients with mean heart rate >100 beats/min, atrial fibrillation, and/or premature ventricular contractions burden ≥10%. Reversal of cardiomyopathy by elimination of the arrhythmia confirms AiCM. Therapeutic choice depends on the culprit arrhythmia, patient comorbidities, and preferences. Following recovery of LV function, patients require continued follow-up if an abnormal myocardial substrate is present. Appropriate diagnosis and treatment of AiCM is likely to improve quality of life and clinical outcomes and to reduce hospital admission and health care spending.     

3-Dimensional Strain Analysis of Hypertrophic Cardiomyopathy: Insights From the NHLBI International HCM Registry

BackgroundAbnormal global longitudinal strain (GLS) has been independently associated with adverse cardiac outcomes in both obstructive and nonobstructive hypertrophic cardiomyopathy.ObjectivesThe goal of this study was to understand predictors of abnormal GLS from baseline data from the National Heart, Lung, and Blood Institute (NHLBI) Hypertrophic Cardiomyopathy Registry (HCMR).MethodsThe study evaluated comprehensive 3-dimensional left ventricular myocardial strain from cine cardiac magnetic resonance in 2,311 patients from HCMR using in-house validated feature-tracking software. These data were correlated with other imaging markers, serum biomarkers, and demographic variables.ResultsAbnormal median GLS (> –11.0%) was associated with higher left ventricular (LV) mass index (93.8 ± 29.2 g/m² vs 75.1 ± 19.7 g/m²; P < 0.0001) and maximal wall thickness (21.7 ± 5.2 mm vs 19.3 ± 4.1 mm; P < 0.0001), lower left (62% ± 9% vs 66% ± 7%; P < 0.0001) and right (68% ± 11% vs 69% ± 10%; P < 0.01) ventricular ejection fractions, lower left atrial emptying functions (P < 0.0001 for all), and higher presence and myocardial extent of late gadolinium enhancement (6 SD and visual quantification; P < 0.0001 for both). Elastic net regression showed that adjusted predictors of GLS included female sex, Black race, history of syncope, presence of systolic anterior motion of the mitral valve, reverse curvature and apical morphologies, LV ejection fraction, LV mass index, and both presence/extent of late gadolinium enhancement and baseline N-terminal pro–B-type natriuretic peptide and troponin levels.ConclusionsAbnormal strain in hypertrophic cardiomyopathy is associated with other imaging and serum biomarkers of increased risk. Further follow-up of the HCMR cohort is needed to understand the independent relationship between LV strain and adverse cardiac outcomes in hypertrophic cardiomyopathy.     

Subtypes of Atrial Functional Mitral Regurgitation: Imaging Insights Into Their Mechanisms and Therapeutic Implications

Functional mitral regurgitation (MR) in patients with atrial fibrillation (AF) without left ventricular dysfunction, namely, atrial functional MR, has been increasingly recognized. Whether mitral annular dilatation causes MR in patients without left ventricular dysfunction has remained controversial; however, recent studies using novel imaging technologies, including 3-dimensional echocardiography, have shown that significant functional MR can sometimes occur in AF patients with significant dilatation of mitral annulus and left atrium. Additional contributors such as atriogenic leaflet tethering, annulus area to leaflet area imbalance resulting from insufficient leaflet remodeling and reduced annular contractility, increased valve stress by flattened saddle shape of the annulus, and left atrial dysfunction may be important triggers of atrial functional MR in the presence of dilated mitral annulus and left atrium. The prevalence of atrial functional MR is reported to be between 3% and 15% in AF patients and those with atrial functional MR are associated with worse clinical outcomes. Because there are few published data regarding therapeutic strategies of atrial functional MR, understanding the principles of therapeutic options and their target mechanisms is important with regards to clinical practice until sufficient evidence is established. In this review, the known mechanisms, clinical implications and, when possible, potential therapeutic options of atrial functional MR are discussed.     

Deep-Learning Models for the Echocardiographic Assessment of Diastolic Dysfunction

ObjectivesThe authors explored a deep neural network (DeepNN) model that integrates multidimensional echocardiographic data to identify distinct patient subgroups with heart failure with preserved ejection fraction (HFpEF).BackgroundThe clinical algorithms for phenotyping the severity of diastolic dysfunction in HFpEF remain imprecise.MethodsThe authors developed a DeepNN model to predict high- and low-risk phenogroups in a derivation cohort (n = 1,242). Model performance was first validated in 2 external cohorts to identify elevated left ventricular filling pressure (n = 84) and assess its prognostic value (n = 219) in patients with varying degrees of systolic and diastolic dysfunction. In 3 National Heart, Lung, and Blood Institute–funded HFpEF trials, the clinical significance of the model was further validated by assessing the relationships of the phenogroups with adverse clinical outcomes (TOPCAT [Aldosterone Antagonist Therapy for Adults With Heart Failure and Preserved Systolic Function] trial, n = 518), cardiac biomarkers, and exercise parameters (NEAT-HFpEF [Nitrate’s Effect on Activity Tolerance in Heart Failure With Preserved Ejection Fraction] and RELAX-HF [Evaluating the Effectiveness of Sildenafil at Improving Health Outcomes and Exercise Ability in People With Diastolic Heart Failure] pooled cohort, n = 346).ResultsThe DeepNN model showed higher area under the receiver-operating characteristic curve than 2016 American Society of Echocardiography guideline grades for predicting elevated left ventricular filling pressure (0.88 vs. 0.67; p = 0.01). The high-risk (vs. low-risk) phenogroup showed higher rates of heart failure hospitalization and/or death, even after adjusting for global left ventricular and atrial longitudinal strain (hazard ratio [HR]: 3.96; 95% confidence interval [CI]: 1.24 to 12.67; p = 0.021). Similarly, in the TOPCAT cohort, the high-risk (vs. low-risk) phenogroup showed higher rates of heart failure hospitalization or cardiac death (HR: 1.92; 95% CI: 1.16 to 3.22; p = 0.01) and higher event-free survival with spironolactone therapy (HR: 0.65; 95% CI: 0.46 to 0.90; p = 0.01). In the pooled RELAX-HF/NEAT-HFpEF cohort, the high-risk (vs. low-risk) phenogroup had a higher burden of chronic myocardial injury (p < 0.001), neurohormonal activation (p < 0.001), and lower exercise capacity (p = 0.001).ConclusionsThis publicly available DeepNN classifier can characterize the severity of diastolic dysfunction and identify a specific subgroup of patients with HFpEF who have elevated left ventricular filling pressures, biomarkers of myocardial injury and stress, and adverse events and those who are more likely to respond to spironolactone.     

Prognostic Impact of Extra–Mitral Valve Cardiac Involvement in Patients With Primary Mitral Regurgitation

BackgroundIn patients with severe primary mitral regurgitation (MR), the indication for surgery is currently based on the presence of symptoms, left ventricular dilatation and dysfunction, atrial fibrillation, and pulmonary hypertension.ObjectivesThe aim of this study was to evaluate the prognostic impact of the presence of extra–mitral valve cardiac involvement (including known risk factors but also severe left atrial [LA] dilatation and right ventricular [RV] dysfunction) in a large multicenter study of patients with primary MR.MethodsPatients with severe primary MR undergoing surgery were included and categorized according to the extent (highest) of cardiac involvement: group 0, no cardiac involvement; group 1, left ventricular involvement; group 2, LA involvement; group 3, pulmonary vasculature or tricuspid valve involvement; or group 4, RV involvement. The outcome was all-cause mortality.ResultsA total of 1,106 patients were included (mean age 63 ± 12 years, 68% male). In total, 377 patients (34%) were classified in group 0, 239 (22%) in group 1, 213 (19%) in group 2, 180 (16%) in group 3, and 97 (9%) in group 4. Kaplan-Meier curve analysis revealed significantly worse survival (log-rank chi-square = 43.4; P < 0.001) with higher group. On multivariable analysis, age, male sex, chronic obstructive pulmonary disease, kidney function, and group of cardiac involvement were independently associated with all-cause mortality. For each increase in group, a 17% higher risk for all-cause mortality was observed (95% CI: 1.051-1.313; P = 0.005) during a median follow-up time of 88 months.ConclusionsIn patients with severe primary MR, a novel classification system based on extra–mitral valve cardiac involvement may help refine risk stratification and timing of surgery, particularly including severe LA dilatation and RV dysfunction in the assessment.     

Left Atrial Strain for Assessment of Left Ventricular Diastolic Function: Focus on Populations With Normal LVEF

Left atrial (LA) strain has emerged as a useful parameter for the assessment of left ventricular (LV) diastolic function and the estimation of LV filling pressures. Some have advocated using LA strain by itself, mainly reservoir strain, as a single stand-alone measurement for this objective. Recent data indicate several challenges for this application in patients with normal left ventricular ejection fraction (LVEF) because of the wide range for normal values and the load dependency of LA strain. Both findings can result in reduced left atrial reservoir strain (LARS) values in normal subjects that overlap those seen in patients with diastolic dysfunction. LARS for the estimation of LV filling pressures is most accurate in patients with depressed LVEF. It is less accurate in patients with normal ejection fraction. In this group of patients, LARS <18% has high specificity for increased LV filling pressures. There are promising data showing the association of LARS with outcome events in patients with normal ejection fraction, and additional data are needed to confirm that it provides incremental information over clinical and other echocardiographic measurements.     

Cardiac Phenotypes and Markers of Adverse Outcome in Elite Athletes With Ventricular Arrhythmias

ObjectivesThis study describes the cardiac phenotypes and markers of adverse outcome in athletes with ventricular arrhythmias with no other discernable etiology than high exercise doses.BackgroundLittle is known about phenotypes and risk markers of life-threatening arrhythmic events in athletes with ventricular arrhythmia.MethodsWe compared high-performance athletes who have ventricular arrhythmia with healthy controls using clinical data and cardiac imaging. None of the patients had family history of arrhythmogenic cardiomyopathy or any other discernable etiology of ventricular arrhythmia. Right (RV) and left ventricular (LV) function was assessed by echocardiographic longitudinal strain (right ventricular free wall strain longitudinal [RVFWSL] and left ventricular global longitudinal strain [LVGLS]). Mechanical dispersion was defined as the standard deviation of time to peak strain in 16 LV segments. RV ejection fraction and presence of late gadolinium enhancement was assessed by cardiac magnetic resonance.ResultsWe included 43 athletes (45 ± 14 years of age, 16% female) with ventricular arrhythmias and 30 healthy athletes (41 ± 9 years of age, 7% female). Athletes with ventricular arrhythmias had worse RV function than healthy athletes by echocardiography (RVFWSL: ?22.9 ± 4.8% vs. ?26.6 ± 3.3%; p < 0.001) and by cardiac magnetic resonance (RV ejection fraction 48 ± 7% vs. 52 ± 6%; p = 0.04), and had more late gadolinium enhancement (24% vs. 3%; p = 0.03). Life-threatening arrhythmic events (aborted cardiac arrest, sustained ventricular tachycardia, or appropriate implantable cardioverter-defibrillator therapy) had occurred in 23 (53%) athletes with ventricular arrhythmias. These had impaired LV function compared to those with less severe ventricular arrhythmias (LVGLS: -17.1 ± 3.0% vs. -18.8 ± 2.0%; p = 0.04). LV mechanical dispersion was an independent marker of life-threatening events (adjusted odds ratio: 2.2 [1.1 to 4.8] by 10 ms increments; p = 0.03).ConclusionsAthletes with ventricular arrhythmias had impaired RV function and more myocardial fibrosis compared to healthy athletes. Athletes with life-threatening arrhythmic events had additional LV contraction abnormalities. These phenotypes mimic arrhythmogenic cardiomyopathy and may potentially be induced by high doses of exercise in susceptible individuals.     

Comprehensive Evaluation of Left Ventricle Dysfunction by a New Computed Tomography Scanner: The E-PLURIBUS Study

BackgroundAlthough cardiac magnetic resonance (CMR) is considered the gold standard for myocardial fibrosis detection, cardiac computed tomography (CCT) is emerging as a promising alternative.ObjectivesThe purpose of this study was to assess feasibility and diagnostic accuracy of a comprehensive functional and anatomical evaluation with CCT as compared with CMR in patients with newly diagnosed left ventricular dysfunction (LVD).MethodsA total of 128 consecutive patients with newly diagnosed LVD were screened. Based on the exclusion criteria, 28 cases were excluded. CCT was performed within 10 days from CMR. Biventricular volumes and ejection fraction, and presence and pattern of delayed enhancement (DE), were determined, along with evaluation of coronary arteries among patients undergoing invasive angiography in the 6 months after CCT.ResultsSix cases were excluded because of claustrophobia at CMR. Among the 94 patients who formed the study population, the concordance between CCT and CMR in suggesting the cause of the LVD was high (94.7%, 89/94 patients) in the overall population and was 100% for identifying ischemic cardiomyopathy. The CCT diagnostic rate for DE assessment was also high (96.7%, 1,544/1,598 territories) and similar to that of CMR (97.4%; P = 0.345, CCT vs CMR). Moreover, CCT showed high diagnostic accuracy in the detection of DE (94.8%, 95% CI: 93.6%-95.8%) in a territory-based analysis. Biventricular volumes and function parameters as measured by CCT and CMR were similar, without significant differences with the exception of a modest difference in RV volume. CCT was confirmed to be accurate for assessing arterial coronary circulation. The mean radiation exposure of the whole CCT was 7.78 ± 2.53 mSv (0.84 ± 0.24 mSv for DE).ConclusionsCCT performed with low-dose whole-heart coverage scanner and high-concentration contrast agent appears an effective noninvasive tool for a comprehensive assessment of patients with newly diagnosed LVD.     

Importancia de los hallazgos de la resonancia magnética cardiaca en el diagnóstico de la miocardiopatía arritmogénica del ventrículo izquierdo

Introduction and objectivesLeft dominant arrhythmogenic cardiomyopathy (LDAC) has recently been recognized as falling on the spectrum of arrhythmogenic cardiomyopathy. It is characterized by fibroadipose replacement of the left ventricle. The aim of this study was to describe the most frequent forms of clinical presentation of LDAC, imaging findings, and events at follow-up, highlighting the importance of cardiac magnetic resonance (CMR).MethodsProspective registry of patients with findings compatible with LDAC. CMR image analysis and clinical follow-up was performed. The primary endpoint was the appearance of major adverse cardiovascular events (MACE) during follow-up, defined as sudden cardiac death, sustained ventricular arrhythmias, and heart transplant.ResultsWe included 74 consecutive patients (mean age, 48.6 years; 50 men [67.6%]). The most frequent CMR indications were chest pain with normal coronary angiography, ventricular arrhythmias, and suspicion of cardiomyopathies. The main CMR findings were midwall and/or subepicardial pattern of late gadolinium enhancement (91.9%), fatty epicardial infiltration (83.8%), and left ventricle segmental contractility abnormalities (47.9%). At a mean follow-up of 3.74 years, 24 patients (32.4%) had a MACE (sudden cardiac death 8.1%, sustained ventricular arrhythmias 21.6%, and heart transplant 4.1%). Independent predictors for the appearance for MACE were a CMR study showing severe late gadolinium enhancement, male sex, and practicing sports.ConclusionsCMR is a key tool for diagnosing LDAC. Characteristic findings are subepicardial fatty infiltration and midwall-subepicardial late gadolinium enhancement. The prognosis of this population is poor with a high incidence of sudden cardiac death and ventricular arrhythmias.     

Basal interventricular septum thinning and long-term left ventricular function in patients with sarcoidosis

BackgroundBasal interventricular septum (IVS) thinning on transthoracic echocardiography (TTE) is highly specific to cardiac sarcoidosis. Although basal IVS thinning is listed as one of the five major diagnostic criteria for cardiac sarcoidosis, its association with long-term cardiac function has not been investigated. This study aimed to evaluate the epidemiology and clinical relevance of basal IVS thinning in a clinic-based cohort of patients with sarcoidosis.MethodsThis retrospective observational study was conducted at a general sarcoidosis clinic. The incidence of basal IVS thinning and associations with variables at baseline and a delayed onset of left ventricular (LV) dysfunction (LV ejection fraction [LVEF] < 50%) were analyzed.ResultsOf the 1009 patients, 23 (2.3%) had basal IVS thinning. Basal IVS thinning was associated with cardiac pacemaker (PM) implantation at baseline (adjusted odds ratio = 20.5; 95% confidence interval [CI] = 7.9–53.2; P < 0.01). Of the 768 patients with an LVEF of ≥50% at baseline who underwent one or more longitudinal TTEs after baseline, 36 (4.7%) developed LV dysfunction over a median observation period of 88.9 months. Basal IVS thinning and PM implantation at baseline were the independent predictors of a delayed onset of LV dysfunction (basal IVS thinning, adjusted hazard ratio [HR] = 3.7; 95% CI = 1.5–9.6; PM implantation, adjusted HR = 15.7; 95% CI = 7.4–33.3).ConclusionsBasal IVS thinning in patients with sarcoidosis can predict a delayed onset of LV dysfunction even when the LV function is preserved at the time of detection.     

Prognostic Value of Global Longitudinal Strain in Hypertrophic Cardiomyopathy: A Systematic Review of Existing Literature

ObjectivesThe association of left ventricular global longitudinal strain (LV-GLS) with clinical outcomes in patients with hypertrophic cardiomyopathy (HCM) has been examined in multiple studies. The authors conducted a systematic review aimed at summarizing and critically appraising the current evidence.BackgroundHCM is a common genetic cardiovascular disease with an estimated prevalence of 1 in 500 patients. LV-GLS derived from speckle tracking echocardiography is a sensitive noninvasive method of assessing regional left ventricular function. Several studies have suggested association of abnormal LV-GLS with outcomes in HCM patients.MethodsA computerized literature search of all English language publications in the PubMed and EMBASE databases was made looking at all randomized and nonrandomized studies conducted on patients with HCM where association of LV-GLS with clinical outcomes was studied. We then manually searched the reference lists of included articles. The Preferred Reporting Items for Systematic reviews and Meta-Analyses statement (PRISMA) of reporting systematic reviews was used.ResultsOur search yielded a total of 14 observational studies published between 2009 and 2017 with a total of 3,154 patients with HCM. Eleven of the 14 studies included a composite cardiac outcome which included mortality as their primary outcome of interest and 3 of the 14 studies looked at association of LV-GLS with ventricular arrhythmias and/or implantable cardiac defibrillator discharge. We noted wide variability in inclusion, methodology, follow-up, and consequently effect estimates, which was not conducive to performing a meta-analysis. However, despite the variation, all studies revealed a degree of association of abnormal LV-GLS with poor cardiac outcomes.ConclusionsOur systematic review of more than 3000 HCM patients suggests an association of abnormal LV-GLS with adverse composite cardiac outcomes and ventricular arrhythmias.     

Imaging Interstitial Fibrosis,Left Ventricular Remodeling,and Function in Stage A and B Heart Failure

Myocardial interstitial fibrosis is part of the advanced disease stage of most cardiovascular pathologies. It has been characterized histologically in various disease settings from hypertensive heart disease and diabetic cardiomyopathy to severe aortic stenosis. It is also involved in the process of aging. In cardiovascular medicine, myocardial interstitial fibrosis is associated with several adverse outcomes, especially heart failure (HF) and sudden cardiac death. Until recently, clinical measures of interstitial fibrosis could only be made by invasive myocardial biopsy. The availability of cardiac magnetic resonance (CMR) T1 mapping techniques allows for the indirect measurement of interstitial space characteristics and extracellular volume size, which is closely correlated with collagen content and interstitial infiltration by amyloid and other molecules. There has been significant improvement in the accuracy and reproducibility of T1 acquisition sequences in the last decade; however, the correct use of this technique requires a solid CMR expertise in daily imaging practice. CMR has become the gold standard to assess left ventricular (LV) remodeling and functional features associated with interstitial fibrosis. These features can be detected in the early stages of HF. The main objective of this paper is to review the relevant results of preclinical and clinical observational studies that demonstrate the prognostic impact of interstitial fibrosis assessed by T1 mapping, as well as adverse left ventricular remodeling, as determinants of HF. Therefore, this review focuses on the pathological mechanisms underlying LV remodeling and interstitial fibrosis, in addition to the technical considerations involved in the assessment of interstitial LV fibrosis by CMR. It provides a thorough review of clinical evidence that demonstrates the association of interstitial fibrosis and other-CMR derived LV phenotypes with Stages A and B HF.     

Using Deep-Learning Algorithms to Simultaneously Identify Right and Left Ventricular Dysfunction From the Electrocardiogram

ObjectivesThis study sought to develop DL models capable of comprehensively quantifying left and right ventricular dysfunction from ECG data in a large, diverse population.BackgroundRapid evaluation of left and right ventricular function using deep learning (DL) on electrocardiograms (ECGs) can assist diagnostic workflow. However, DL tools to estimate right ventricular (RV) function do not exist, whereas those to estimate left ventricular (LV) function are restricted to quantification of very low LV function only.MethodsA multicenter study was conducted with data from 5 New York City hospitals: 4 for internal testing and 1 serving as external validation. We created novel DL models to classify left ventricular ejection fraction (LVEF) into categories derived from the latest universal definition of heart failure, estimate LVEF through regression, and predict a composite outcome of either RV systolic dysfunction or RV dilation.ResultsWe obtained echocardiogram LVEF estimates for 147,636 patients paired to 715,890 ECGs. We used natural language processing (NLP) to extract RV size and systolic function information from 404,502 echocardiogram reports paired to 761,510 ECGs for 148,227 patients. For LVEF classification in internal testing, area under curve (AUC) at detection of LVEF ≤40%, 40% < LVEF ≤50%, and LVEF >50% was 0.94 (95% CI: 0.94-0.94), 0.82 (95% CI: 0.81-0.83), and 0.89 (95% CI: 0.89-0.89), respectively. For external validation, these results were 0.94 (95% CI: 0.94-0.95), 0.73 (95% CI: 0.72-0.74), and 0.87 (95% CI: 0.87-0.88). For regression, the mean absolute error was 5.84% (95% CI: 5.82%-5.85%) for internal testing and 6.14% (95% CI: 6.13%-6.16%) in external validation. For prediction of the composite RV outcome, AUC was 0.84 (95% CI: 0.84-0.84) in both internal testing and external validation.ConclusionsDL on ECG data can be used to create inexpensive screening, diagnostic, and predictive tools for both LV and RV dysfunction. Such tools may bridge the applicability of ECGs and echocardiography and enable prioritization of patients for further interventions for either sided failure progressing to biventricular disease.     

Progression of Myocardial Fibrosis in Hypertrophic Cardiomyopathy: A Cardiac Magnetic Resonance Study

ObjectivesThis study examined fibrosis progression in hypertrophic cardiomyopathy (HCM) patients, as well as its relationship to patient characteristics, clinical outcomes, and its effect on clinical decision making.BackgroundMyocardial fibrosis, as quantified by late gadolinium enhancement (LGE) in cardiac magnetic resonance (CMR), provides valuable prognostic information in patients with HCM.MethodsA total of 157 patients with HCM were enrolled in this study, with 2 sequential CMR scans separated by an interval of 4.7 ± 1.9 years.ResultsAt the first CMR session (CMR-1), 70% of patients had LGE compared with 85% at CMR-2 (p = 0.001). The extent of LGE extent increased between the 2 CMR procedures, from 4.0 ± 5.6% to 6.3 ± 7.4% (p < 0.0001), with an average LGE progression rate of 0.5 ± 1.0%/year. LGE mass progression was correlated with higher LGE mass and extent on CMR-1 (p = 0.0017 and p = 0.007, respectively), greater indexed left ventricular (LV) mass (p < 0.0001), greater LV maximal wall thickness (p < 0.0001), apical aneurysm at CMR-1 (p < 0.0001), and lower LV ejection fraction (EF) (p = 0.029). Patients who were more likely to have a higher rate of LGE progression presented with more severe disease at baseline, characterized by LGE extent >8% of LV mass, indexed LV mass >100 g/m², maximal wall thickness ≥20 mm, LVEF ≤60%, and apical aneurysm. There was a significant correlation between the magnitude of LGE progression and future implantation of insertable cardioverter-defibrillators (p = 0.004), EF deterioration to ≤50% (p < 0.0001), and admission for heart failure (p = 0.0006).ConclusionsMyocardial fibrosis in patients with HCM is a slowly progressive process. Progression of LGE is significantly correlated with a number of clinical outcomes such as progression to EF ≤50% and heart failure admission. Judicious use of serial CMR with LGE can provide valuable information to help patient management.     

Mechanical Effects on Right Ventricular Function From Left Bundle Branch Block and Cardiac Resynchronization Therapy

ObjectivesThe purpose of this study was to investigate how LBBB and CRT modify RV free wall function by direct ventricular interaction.BackgroundRight ventricular (RV) function influences prognosis in patients with left bundle branch block (LBBB) and cardiac resynchronization therapy (CRT). There is, however, limited insight into how LBBB and CRT affect RV function.MethodsIn 24 patients with LBBB with nonischemic cardiomyopathy, RV and left ventricular (LV) strain by speckle-tracking echocardiography was measured before and after CRT. Underlying mechanisms were studied in 16 anesthetized dogs with ultrasonic dimension crystals and micromanometers.ResultsPatients with LBBB demonstrated distinct early systolic shortening in the RV free wall, which coincided with the typical abnormal early systolic septal shortening. In animals, this RV free wall contraction pattern resulted in reduced myocardial work as a large portion of the shortening occurred against low pressure during early systole, coinciding with abnormal leftward septal motion. RV systolic function was maintained by vigorous contraction in the late-activated LV lateral wall, which pushed the septum toward the RV. CRT reduced abnormal septal motion and increased RV free wall work because there was less inefficient shortening against low pressure.ConclusionsLBBB reduces workload on the RV free wall because of abnormal septal motion and delayed activation of the LV lateral wall. Restoring septal and LV function by CRT increases workload in RV free wall and may explain why patients with RV failure respond poorly to CRT. (Contractile Reserve in Dyssynchrony: A Novel Principle to Identify Candidates for Cardiac Resynchronization Therapy [CRID-CRT]; NCT02525185)     

Cardiac Imaging for Coronary Heart Disease Risk Stratification in Chronic Kidney Disease

Chronic kidney disease (CKD), defined as dysfunction of the glomerular filtration apparatus, is an independent risk factor for the development of coronary artery disease (CAD). Patients with CKD are at a substantially higher risk of cardiovascular mortality compared with the age- and sex-adjusted general population with normal kidney function. The risk of CAD and mortality in patients with CKD is correlated with the degree of renal dysfunction including presence of microalbuminuria. A greater cardiovascular risk, albeit lower than for patients receiving dialysis, persists even after kidney transplantation. Congestive heart failure, commonly caused by CAD, also accounts for a significant portion of the cardiovascular-related events observed in CKD. The optimal strategy for the evaluation of CAD in patients with CKD, particularly before renal transplantation, remains a topic of contention spanning over several decades. Although the evaluation of coexisting cardiac disease in patients with CKD is desirable, severe renal dysfunction limits the use of radiographic and magnetic resonance contrast agents due to concerns regarding contrast-induced nephropathy and nephrogenic systemic sclerosis, respectively. In addition, many patients with CKD have extensive and premature (often medial) calcification disproportionate to the severity of obstructive CAD, thereby limiting the diagnostic value of computed tomography angiography. As such, echocardiography, non–contrast-enhanced magnetic resonance, nuclear myocardial perfusion, and metabolic imaging offer a variety of approaches to assess obstructive CAD and cardiomyopathy of advanced CKD without the need for nephrotoxic contrast agents.     

Screening of Potential Cardiac Involvement in Competitive Athletes Recovering From COVID-19: An Expert Consensus Statement

As our understanding of the complications of coronavirus disease-2019 (COVID-19) evolve, subclinical cardiac pathology such as myocarditis, pericarditis, and right ventricular dysfunction in the absence of significant clinical symptoms represents a concern. The potential implications of these findings in athletes are significant given the concern that exercise, during the acute phase of viral myocarditis, may exacerbate myocardial injury and precipitate malignant ventricular arrhythmias. Such concerns have led to the development and publication of expert consensus documents aimed at providing guidance for the evaluation of athletes after contracting COVID-19 in order to permit safe return to play. Cardiac imaging is at the center of these evaluations. This review seeks to evaluate the current evidence regarding COVID-19–associated cardiovascular disease and how multimodality imaging may be useful in the screening and clinical evaluation of athletes with suspected cardiovascular complications of infection. Guidance is provided with diagnostic “red flags” that raise the suspicion of pathology. Specific emphasis is placed on the unique challenges posed in distinguishing athletic cardiac remodeling from subclinical cardiac disease. The strengths and limitations of different imaging modalities are discussed and an approach to return to play decision making for athletes post–COVID-19, as informed by multimodality imaging, is provided.     

Structural and Physiological Imaging to Predict the Risk of Lethal Ventricular Arrhythmias and Sudden Death

Identifying patients at risk of sudden cardiac death remains a major challenge in cardiovascular medicine. Advances in cardiovascular imaging have identified several anatomic and functional variables that can be quantified as continuous variables to predict the risk of developing lethal ventricular tachyarrhythmias in patients with depressed left ventricular (LV) systolic function. Some, such as LV mass, volume, and the dyssynchrony of contraction, can be derived from currently available echocardiographic and nuclear imaging modalities. Others require advanced cardiac imaging modalities with quantification of myocardial scar with gadolinium-enhanced cardiac magnetic resonance and myocardial sympathetic denervation using norepinephrine analogs and positron emission tomography or single-photon emission computed tomography offering the most promise. There is an immediate need to develop a sequential cost-effective approach that capitalizes on readily available clinical information complemented with advanced imaging modalities in selected patients to improve risk stratification for arrhythmic death beyond LV ejection fraction.