Class 1C Antiarrhythmics for Premature Ventricular Complex Suppression in Nonischemic Cardiomyopathy With Implantable Cardioverter-Defibrillators.

BACKGROUND: Premature ventricular complexes (PVCs) are common and associated with worse outcomes in patients with heart failure. Class 1C antiarrhythmic drugs (AADs) effectively suppress PVCs, but guidelines currently restrict their use in structural heart disease. OBJECTIVES: This study aimed to assess the safety and efficacy of class 1C AADs in patients with nonischemic cardiomyopathy (NICM) and implantable cardioverter-defibrillators (ICDs). METHODS: All patients with NICM and an ICD treated with flecainide or propafenone at the Hospital of the University of Pennsylvania between 2014 and 2022 were identified. PVC burden, left ventricular ejection fraction (LVEF), and biventricular pacing percentage were compared before and during class 1C AAD treatment. Safety outcomes included sustained atrial and ventricular arrhythmias, heart failure admissions, and death. RESULTS: We identified 34 patients, 23 receiving flecainide and 11 propafenone. Most patients (62%) had failed other AADs or catheter ablation (68%) prior to class 1C AAD initiation. PVC burden decreased from 20 ± 13% to 6 ± 7% (P < 0.001), LVEF increased from 33 ± 9% to 37 ± 10% (P = 0.01), and biventricular pacing percentage increased from 85 ± 9% to 93 ± 7% (P = 0.01). Sustained ventricular tachycardia (2 vs 9 patients) and admissions for decompensated heart failure (2 vs 3 patients) decreased compared with the 12 months prior to class 1C AAD initiation. CONCLUSIONS: Class 1C AADs effectively suppressed PVCs in patients with NICM and ICDs, leading to increases in LVEF and biventricular pacing percentage. In this limited sample, their use was safe. Larger studies are needed to confirm the safety of this approach.

Predictors of nonpulmonary vein triggers for atrial fibrillation: A clinical risk score.

BACKGROUND: Targeting non-pulmonary vein triggers (NPVTs) after pulmonary vein isolation may reduce atrial fibrillation (AF) recurrence. Isoproterenol infusion and cardioversion of spontaneous or induced AF can provoke NPVTs but typically require vasopressor support and increased procedural time. OBJECTIVE: The purpose of this study was to identify risk factors for the presence of NPVTs and create a risk score to identify higher-risk subgroups. METHODS: Using the AF ablation registry at the Hospital of the University of Pennsylvania, we included consecutive patients who underwent AF ablation between January 2021 and December 2022. We excluded patients who did not receive NPVT provocation testing after failing to demonstrate spontaneous NPVTs. NPVTs were defined as non-pulmonary vein ectopic beats triggering AF or focal atrial tachycardia. We used risk factors associated with NPVTs with P <.1 in multivariable logistic regression model to create a risk score in a randomly split derivation set (80%) and tested its predictive accuracy in the validation set (20%). RESULTS: In 1530 AF ablations included, NPVTs were observed in 235 (15.4%). In the derivation set, female sex (odds ratio [OR] 1.40; 95% confidence interval [CI] 0.96-2.03; P = .080), sinus node dysfunction (OR 1.67; 95% CI 0.98-2.87; P = .060), previous AF ablation (OR 2.50; 95% CI 1.70-3.65; P <.001), and left atrial scar (OR 2.90; 95% CI 1.94-4.36; P <.001) were risk factors associated with NPVTs. The risk score created from these risk factors (PRE2SSS2 score; [PRE]vious ablation: 2 points, female [S]ex: 1 point, [S]inus node dysfunction: 1 point, left atrial [S]car: 2 points) had good predictive accuracy in the validation cohort (area under the receiver operating characteristic curve 0.728; 95% CI 0.648-0.807). CONCLUSION: A risk score incorporating predictors for NPVTs may allow provocation of triggers to be performed in patients with greatest expected yield.

Relationship between baseline electrocardiographic measurements and outcomes in patients with high-risk heart failure: Insights from the VerICiguaT Global Study in Subjects with Heart Failure with Reduced Ejection Fraction (VICTORIA) trial.

AIMS: Whether electrocardiographic (ECG) measurements predict mortality in chronic heart failure with reduced ejection fraction (HFrEF) is unknown. METHODS AND RESULTS: We studied 4880 patients from the Vericiguat Global Study in Subjects with Heart Failure with Reduced Ejection Fraction (VICTORIA) trial with a baseline 12-lead ECG. Associations between ECG measurements and mortality were estimated as hazard ratios (HR) and adjusted for the Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC) risk score, N-terminal pro-B-type natriuretic peptide, and index event. Select interactions between ECG measurements, patient characteristics and mortality were examined. Over a median of 10.8 months, there were 824 cardiovascular (CV) deaths (214 sudden) and 1005 all-cause deaths. Median age was 68 years (interquartile range [IQR] 60-76), 24% were women, median ejection fraction was 30% (IQR 23-35), 41% had New York Heart Association class III/IV, and median MAGGIC score was 24 (IQR 19-28). After multivariable adjustment, significant associations existed between heart rate (per 5 bpm: HR 1.02), QRS duration (per 10 ms: HR 1.02), absence of left ventricular hypertrophy (HR 0.64) and CV death, and similarly so with all-cause death (HR 1.02; HR 1.02; HR 0.61, respectively). Contiguous pathologic Q waves were significantly associated with sudden death (HR 1.46), and right ventricular hypertrophy with all-cause death (HR 1.44). The only sex-based interaction observed was for pathologic Q waves on CV (men: HR 1.05; women: HR 1.64, pinteraction = 0.024) and all-cause death (men: HR 0.99; women: HR 1.57; pinteraction = 0.010). Whereas sudden death doubled in females, it did not differ among males (male: HR 1.25, 95% confidence interval [CI] 0.87-1.79; female: HR 2.50, 95% CI 1.23-5.06; pinteraction = 0.141). CONCLUSION: Routine ECG measurements provide additional prognostication of mortality in high-risk HFrEF patients, particularly in women with contiguous pathologic Q waves.

Review of Hydroxychloroquine Cardiotoxicity: Lessons From the COVID-19 Pandemic.

PURPOSE OF REVIEW: The coronavirus disease 2019 (COVID-19) pandemic has popularized the usage of hydroxychloroquine and chloroquine (HCQ/CQ) as treatments for COVID-19. Previously used as anti-malarial and now commonly used in rheumatologic conditions, preliminary in vitro studies have demonstrated these medications also have anti-viral properties. Retinopathy and neuromyopathy are well recognized complications of using these treatments; however, cardiotoxicity is under-recognized. This review will discuss the implications and cardiotoxicity of HCQ/CQ, their mechanisms of action, and their utility in COVID-19. RECENT FINDINGS: Early clinical trials demonstrated a modest benefit of HCQ in COVID-19, causing a push for the usage of it. However, further large multi-center randomized control centers, demonstrated no benefit, and even a trend towards worse outcomes. The predominant cardiac complication observed with HCQ in COVID-19 was cardiac arrhythmias and prolonging of the QT interval. However, with chronic usage of HCQ/CQ, the development of heart failure (HF) and cardiomyopathy (CM) can occur. Although, most adverse cardiac events related to HCQ/CQ usage in COVID-19 were secondary to conduction disorders given the short duration of treatment, HCQ/CQ can cause CM and HF, with chronic usage. Given the insufficient evidence, HCQ/CQ usage in COVID-19 is not routinely recommended, especially with novel therapies now being developed and used. Additionally, usage of HCQ/CQ should prompt initial cardiac evaluation with ECG, and yearly monitoring, with consideration for advanced imaging if clinically warranted. The diagnosis of HCQ/CQ cardiomyopathy is important, as prompt cessation can allow for recovery when these changes are still reversible.

Nationwide Study of Sex Differences in Incident Heart Failure in Newly Diagnosed Nonvalvular Atrial Fibrillation.

Background: Heart failure (HF) is a leading complication of nonvalvular atrial fibrillation (NVAF), and the presence of both conditions worsens prognosis. Sex-specific associations between NVAF and outcomes focus on stroke; less is known about HF. We evaluated sex differences in incident HF in NVAF. Methods: We identified adults age ≥ 65 years hospitalized for incident NVAF without prior HF from April 2010 to March 2018 in Canada. The primary outcome was incident HF hospitalization, with a secondary composite outcome of incident HF hospitalization or all-cause mortality at 1 year. Cox proportional hazard regression models were constructed for the association between sex and outcomes, adjusting for age, comorbidities, socioeconomic status, cardioversion, and medications. Results: Of 68,909 NVAF patients, 53.8% were women. Women had a higher rate of the primary outcome (30.0% vs 25.6%, P < 0.001) and the composite outcome (39.5% vs 36.6%, P < 0.001) than men. In multivariable analysis without adjusting for medications, there was an 8% increase risk of HF (95% confidence interval [CI] 1.05-1.11, P < 0.001) for women, which was attenuated when accounting for medication (hazard ratio [HR] 1.01, 95% CI 0.98-1.04). After full adjustment, women age ≥ 75 years were at higher risk of the primary outcome (HR 1.10, 95% CI 1.06-1.13, P < 0.001) and the composite outcome (HR 1.04, 95% CI 1.01-1.07, P < 0.001), compared with men, whereas there was a significantly lower risk for those age 65-75 years. Conclusions: In this nationwide study of incident NVAF without HF, women age ≥ 75 years were more likely to develop HF or die than men. Strategies to prevent HF in older women with NVAF are needed.

Contexte: L'insuffisance cardiaque (IC) est une complication majeure de la fibrillation auriculaire non valvulaire (FANV), et la présence des deux affections assombrit le pronostic. Les associations entre la FANV et ses complications en fonction du sexe ont surtout porté sur l'AVC; on en connaît moins sur l'IC. Nous avons évalué les différences entre les sexes pour l'IC fortuite dans la FANV. Méthodologie: Nous avons identifié des adultes de ≥ 65 ans, sans antécédents d'IC, hospitalisés pour une FANV fortuite entre avril 2010 et mars 2018 au Canada. L'hospitalisation à la suite d'une IC fortuite constituait le critère d'évaluation principal, le critère d'évaluation secondaire composé comprenait les hospitalisations pour un épisode d'IC fortuite ou le décès toutes causes confondues à un an. Des modèles de régression à risques proportionnels de Cox ont servi à évaluer l'association entre le sexe et les résultats, après correction en fonction de l'âge, des comorbidités, de la situation socio-économique, de la cardioversion et de la médication. Résultats: Le groupe étudié comptait 68 909 patients atteints de FANV dont 53,8 % étaient des femmes. Les femmes étaient plus nombreuses à répondre au critère d'évaluation principal (30,0 % vs 25,6 %, p < 0,001) et au critère d'évaluation composé (39,5 % vs 36,6 %, p < 0,001). Dans une analyse multivariée ne comportant aucune correction en fonction de la médication, une augmentation de 8 % du risque d'IC (intervalle de confiance [IC] à 95 % : 1,05-1,11, p < 0,001) a été notée chez les femmes. Cette augmentation se trouvait atténuée lorsque la médication était prise en compte (rapport des risques instantanés [RRI] : 1,01, IC à 95 % : 0,98-1,04). Après correction complète, les femmes de ≥ 75 ans ont été associées à un risque plus élevé d'atteindre le critère d'évaluation principal (RRI : 1,10, IC à 95 % : 1,06-1,13, p < 0,001) et le critère d'évaluation composé (RRI : 1,04, IC à 95 % : 1,01-1,07, p < 0,001) comparativement aux hommes; en revanche, le risque était significativement plus faible chez les femmes de 65-75 ans. Conclusions: Dans cette étude nationale sur la FANV fortuite sans IC, les femmes de ≥ 75 ans étaient plus susceptibles de développer une IC ou de décéder que les hommes d'où la nécessité de mettre en place des stratégies de prévention de l'IC chez les femmes plus âgées atteintes de FANV.

Trends in Uptake and Adherence to Oral Anticoagulation for Patients With Incident Atrial Fibrillation at High Stroke Risk Across Health Care Settings.

Background Oral anticoagulation (OAC) therapy prevents morbidity and mortality in nonvalvular atrial fibrillation; whether location of diagnosis influences OAC uptake or adherence is unknown. Methods and Results Retrospective cohort study (2008-2019), identifying adults with incident nonvalvular atrial fibrillation across health care settings (emergency department, hospital, outpatient) at high risk of stroke. OAC uptake and adherence via proportion of days covered for direct OACs and time in therapeutic range for warfarin were measured. Proportion of days covered was categorized as low (0-39%), intermediate (40-79%), and high (80-100%). Warfarin control was defined as time in therapeutic range ≥65%. All-cause mortality was examined at a 3-year landmark. Among 75 389 patients with nonvalvular atrial fibrillation (47.0% women, mean 77.4 years), 19.7% were diagnosed in the emergency department, 59.1% in the hospital, and 21.2% in the outpatient setting. Ninety-day OAC uptake was 51.6% in the emergency department, 50.9% in the hospital, and 67.9% in the outpatient setting (P<0.0001). High direct OAC adherence increased from 64.9% to 80.3% in the emergency department, 64.3% to 81.7% in the hospital, and 70.9% to 88.6% in the outpatient setting over time (P values for trend <0.0001). Warfarin control was 40.3% overall and remained unchanged. In multivariable analysis, outpatient diagnosis compared with the hospital was associated with greater OAC uptake (odds ratio [OR], 1.79; [95% CI, 1.72-1.87]) and direct OAC (OR, 1.42; [95% CI, 1.27-1.59]) and warfarin (OR, 1.49; [95% CI, 1.36-1.63]) adherence. Varying or persistently low adherence was associated with a poor prognosis, especially for warfarin. Conclusions Locale of nonvalvular atrial fibrillation diagnosis is associated with varying OAC uptake and adherence. Interventions specific to health care settings are needed to improve stroke prevention.

Outcomes of pregnancy in women with hypertrophic cardiomyopathy: A systematic review.

INTRODUCTION: Hypertrophic cardiomyopathy (HCM) is a genetic disorder that can be complicated by heart failure and sudden cardiac death. Pregnancy causes hemodynamic changes, which may be deleterious in patients with HCM. Existing cohort studies, analyzing maternal and fetal outcomes of pregnant HCM patients, are limited by small sample sizes. We performed a systematic review of maternal and fetal outcomes of pregnancy in patients with HCM. METHODS: We performed a literature search for studies reporting maternal or fetal outcomes in pregnant women with HCM. Primary outcomes included maternal death, stillbirth, and fetal death. Secondary maternal outcomes included both sustained and non-sustained ventricular tachycardia (VT), atrial fibrillation, heart failure (HF), syncope, cesarean delivery, and preeclampsia/eclampsia. The secondary fetal outcome was preterm birth. We used a random-effects model to determine pooled incidences of outcomes. RESULTS: We identified a total of 18 studies with 1624 pregnancies. The incidence of maternal death was 0.2%. The rates of sustained VT, any VT (including non-sustained), AF, HF, and syncope were 1% (0-1%), 6% (4-8%), 4% (2-6%), 5% (3-8%), and 9% (3-14%), respectively. Postpartum hemorrhage, preeclampsia/eclampsia, and cesarean section complicated 2% (1-4%), 4% (2-6%), and 43% (32-54%) of pregnancies, respectively. Neonatal death occurred in 0.2% of pregnancies. Stillbirth complicated 1% (95% CI, 0-3%) of pregnancies, whereas the incidence of preterm birth was 22% (95% CI, 18-25%). CONCLUSIONS: Women with HCM considering pregnancy can be reassured that the risk of maternal, fetal, or neonatal death is low. However, they are at risk of several non-fatal cardiac and pregnancy-related complications.

Clinical utility of 12-lead electrocardiogram in evaluating heart disease in patients with muscular dystrophy: Assessment of left ventricular hypertrophy, conduction disease, and cardiomyopathy.

INTRODUCTION: Heart disease remains a leading cause of mortality in patients with muscular dystrophy (MD), and cardiac assessment by standard imaging modalities is challenging due to the prominence of physical limitations. METHODS: In this prospective cohort study of 169 MD patients and 34 negative control patients, we demonstrate the clinical utility of a 12-lead electrocardiogram (ECG) as an effective modality for the assessment of cardiac status in patients with MD. We assessed the utility of conventional criteria for electrocardiogram-indicated left ventricular hypertrophy (ECG-LVH) as well as ECG morphologies. RESULTS: Cornell voltage, Cornell voltage-duration, Sokolow-Lyon voltage, and Romhilt-Estes point score criteria demonstrated low sensitivity and minimal positive predictive value for ECG-LVH when compared with cardiac imaging. Patients with LBBB had a high probability of a cardiomyopathy (relative risk [RR], 2.75; 95% confidence interval [CI], 2.14-3.53; p < .001), and patients with QRS fragmentation (fQRS) had a high probability of a cardiomyopathy (RR, 1.76; 95% CI, 1.20-2.59; p = .004), requiring cardiac medication and device intervention. We found that an R/S ratio >1 in V1 and V2 is highly specific (specificity, 0.89; negative predictive value [NPV], 0.89 and specificity, 0.82; NPV, 0.89, respectively) for patients with dystrophinopathies compared with other types of MD. CONCLUSION: The identification of LBBB and fQRS was linked to cardiomyopathy in patients with MD, while ECG-LVH was of limited utility. Importantly, these findings can be applied to effectively screen a broad cohort of MD patients for structural heart disease and prompt further evaluation and therapeutic intervention.

Plasma Exchange for Immune Checkpoint Inhibitor-Induced Myocarditis.

Immune checkpoint inhibitor therapy has been shown to improve outcomes across many types of malignancies. However, immune checkpoint inhibitor has been associated with several immune-related adverse events including myocarditis. We describe the case of a 69-year-old man with fulminant myocarditis likely due to pembrolizumab therapy, complicated by biventricular failure with cardiogenic shock. Because of deterioration in hemodynamic status refractory to conventional immunosuppression, therapeutic plasma exchange was performed, resulting in a rapid reduction of serum pembrolizumab levels, and marked clinical, radiological, and biochemical improvement. To our knowledge, this is the first reported case on the successful use of plasma exchange for pembrolizumab-associated fulminant myocarditis.

Il a été montré que le traitement par un inhibiteur du point de contrôle immunitaire améliore les résultats dans de nombreux types de cancer. Un inhibiteur du point de contrôle immunitaire a toutefois été associé à plusieurs effets indésirables d'origine immunologique, y compris la myocardite. Nous vous présentons le cas d'un homme de 69 ans ayant présenté une myocardite fulminante, probablement causée par un traitement par le pembrolizumab, compliquée par une insuffisance biventriculaire accompagnée d'un choc cardiogénique. En raison de la détérioration de l'état hémodynamique réfractaire à une immunosuppression classique, un échange plasmatique thérapeutique a été effectué, lequel a entraîné une réduction rapide des taux sériques de pembrolizumab, et une amélioration marquée sur les plans clinique, radiologique et biochimique. À notre connaissance, il s'agit du premier cas signalé dans lequel un échange plasmatique a été utilisé avec succès pour traiter une myocardite fulminante associée au pembrolizumab.

Cardiomyopathies and Genetic Testing in Heart Failure: Role in Defining Phenotype-Targeted Approaches and Management.

Cardiomyopathies represent an important cause of heart failure, often affecting young individuals, and have important implications for relatives. Genetic testing for cardiomyopathies is an established care pathway in contemporary cardiology practice. The primary cardiomyopathies where genetic testing is indicated are hypertrophic, dilated, arrhythmogenic, and restrictive cardiomyopathies, with left ventricular noncompaction as a variant phenotype. Early identification and initiation of therapies in patients with inherited cardiomyopathies allow for targeting asymptomatic and presymptomatic patients in stages A and B of the American College of Cardiology/American Heart Association classification of heart failure. The current approach for genetic testing uses gene panel-based testing with the ability to extend to whole-exome and whole-genome sequencing in rare instances. The central components of genetic testing include defining the genetic basis of the diagnosis, providing prognostic information, and the ability to screen and risk-stratify relatives. Genetic testing for cardiomyopathies should be coordinated by a multidisciplinary team including adult and pediatric cardiologists, genetic counsellors, and geneticists, with access to expertise in cardiac imaging and electrophysiology. A pragmatic approach for addressing genetic variants of uncertain significance is important. In this review, we highlight the indications for genetic testing in the various cardiomyopathies, the value of early diagnosis and treatment, family screening, and the care process involved in genetic counselling and testing.

Sex and Medium-term Outcomes of ST-Segment Elevation Myocardial Infarction in Kerala, India: A Propensity Score-Matched Analysis.

BACKGROUND: Sex-based differences have been found in outcomes following ST-segment myocardial infarction (STEMI). Studies assessing sex-based differences in STEMI among Indian patients have reported conflicting results. METHODS: A prospective multicenter registry of consecutive patients with STEMI who presented to percutaneous coronary intervention (PCI)-capable hospitals in the Indian state of Kerala between June 2013 and March 2017 was used to assess 1-year outcomes. The primary endpoint was a composite of major adverse cardiac events (MACE), including death, stroke, nonfatal myocardial infarction, and rehospitalization for heart failure. Outcomes of 2 sex-based propensity score-matched groups were compared. RESULTS: We included 3194 patients (19.4% women). Women presenting with STEMI were older, had more traditional cardiovascular risk factors, and were more likely to be classified as living in poverty. After propensity-score matching, women experienced greater incidence of MACE (20.9% vs 14.3%, P < 0.01), primarily driven by increased 1-year mortality (14.3% vs 8.6%, P < 0.01). Women were more likely to experience prehospital delays, compared with men. Although reperfusion rates were similar between the groups, men were more likely than women to undergo reperfusion within the first 12 hours of chest pain onset. Among patients undergoing primary PCI, women were more likely to have delayed PCI than were men (80.2% vs 72.9%, P = 0.03). Procedural characteristics were similar between groups. CONCLUSIONS: Women in this cohort experienced higher incidence of MACE at 1 year, compared to men, primarily owing to increased mortality. Timeliness of reperfusion appears to be the primary factor impacting differences in outcomes between the 2 groups and may represent an attractive target for quality-improvement initiatives.

CONTEXTE: Des différences entre les sexes ont été constatées dans les résultats obtenus à la suite d'un infarctus du myocarde avec élévation du segment ST (STEMI). Des études évaluant les différences entre les sexes parmi des patients indiens ayant subi un STEMI ont produit des résultats contradictoires. MÉTHODOLOGIE: Un registre multicentrique et prospectif de patients consécutifs qui ont subi un STEMI et se sont présentés dans des hôpitaux où pouvait être pratiquée une intervention coronarienne percutanée (ICP) dans l'État indien du Kerala entre juin 2013 et mars 2017 a été utilisé pour évaluer les résultats à 1 an. Le paramètre d'évaluation principal regroupait des événements cardiaques indésirables majeurs (ECIM) comprenant le décès, l'accident vasculaire cérébral, l'infarctus du myocarde non fatal et la réhospitalisation pour cause d'insuffisance cardiaque. Les résultats de deux groupes appariés selon les scores de propension en fonction du sexe ont été comparés. RÉSULTATS: Nous avons inclus 3 194 patients (19,4 % de femmes). Les femmes qui avaient subi un STEMI étaient plus âgées, présentaient des facteurs de risque cardiovasculaire plus classiques et étaient plus susceptibles d'appartenir à la catégorie des personnes vivant dans la pauvreté. Après l'appariement selon les scores de propension, l'incidence des ECIM était plus élevée chez les femmes (20,9 % vs 14,3 %, p < 0,01), surtout en raison d'une mortalité accrue à 1 an (14,3 % vs 8,6 %, p < 0,01). Les femmes étaient plus susceptibles de subir des retards avant l'hospitalisation que les hommes. Bien que les taux de reperfusion étaient semblables dans les groupes étudiés, les hommes étaient plus susceptibles que les femmes de subir une reperfusion dans les 12 premières heures suivant l'apparition de la douleur thoracique. Parmi les patients ayant subi une ICP primaire, les femmes étaient plus susceptibles d'être touchées par un retard d'intervention que les hommes (80,2 % vs 72,9 %, p = 0,03). Les caractéristiques de l'intervention étaient similaires dans les groupes étudiés. CONCLUSIONS: L'incidence des ECIM à 1 an au sein de cette cohorte était plus élevée chez les femmes que chez les hommes, surtout en raison d'une mortalité accrue. La rapidité de la reperfusion semble être le principal facteur ayant des répercussions sur les différences de résultats entre les deux groupes et pourrait représenter une cible intéressante dans le cadre d'initiatives d'amélioration de la qualité.

Cardiac Intervention Improves Heart Disease and Clinical Outcomes in Patients With Muscular Dystrophy in a Multidisciplinary Care Setting.

Background Patients with muscular dystrophy (MD) represent a vulnerable patient population with no clearly defined care model in modern-day clinical practice to manage a high burden of heart disease and comorbidities. We demonstrate the effectiveness of cardiac interventions, namely the initiation and optimization of medical and device therapies, as part of a multidisciplinary care approach to improve clinical outcomes in patients with MD. Methods and Results We conducted a prospective cohort study at the Neuromuscular Multidisciplinary clinic following patients with dystrophinopathies, limb-girdle MD, type 1 myotonic dystrophy, and facioscapulohumeral MD. A negative control group classified as non-MD myopathies without heart disease, was also tracked. Our cohort of 185 patients (median age: 42 years; 79 [42.7%] women), included 145 patients with MD. Cardiomyopathy was present in 65.6% of the patients with dystrophinopathies (21 of 32) and 27.3% of the patients with limb-girdle MD (9 of 33). Conduction abnormalities were common in type 1 myotonic dystrophy (33.3% [20/60] patients). Cardiac intervention reversed systolic dysfunction, with left ventricular ejection fraction improving from 43% to 50.0% over a 3-year period. A sustained reduction in healthcare utilization was also observed. The number of outpatient clinic visits decreased from 3.0 to 1.5 visits per year, the duration of hospitalizations was reduced from 14.2 to 0.9 days per year, and the number of cardiac-related hospitalizations decreased from 0.4 to 0.1 hospitalizations per year associated with low mortality. Conclusions Our study demonstrates that cardiac intervention as part of a comprehensive multidisciplinary care approach to treating patients with MD leads to a sustained improvement in clinical outcomes.

Comparison of Usefulness of Cardiac Resynchronization Therapy in Patients With Type 1 Myotonic Dystrophy With Versus Without Left Bundle Branch Block.

Patients with type 1 myotonic dystrophy show reduced left ventricular systolic function in the presence of left bundle branch block due to electromechanical dys-synchrony. Our prospective study tracked a cohort of 64 type 1 myotonic dystrophy patients that demonstrated a high burden of atrial and ventricular arrhythmias and conduction delays. Of these patients, 12 (19%) patients had left bundle branch block, which was associated with reduced left ventricular systolic function. Eight of these patients received cardiac resynchronization therapy devices resulting in reduction of median QRS complex duration from 173 to 166 ms (p = 0.04), and improvement in median left ventricular ejection fraction from 37% to 46% (p = 0.007). In conclusion, cardiac resynchronization therapy device therapy is both feasible and effective in treating advanced cardiac disease in this vulnerable group of patients by improving left ventricular function.

Cardiorenal Syndrome and Heart Failure-Challenges and Opportunities.

Cardiorenal syndromes (CRS) describe concomitant bidirectional dysfunction of the heart and kidneys in which 1 organ initiates, perpetuates, and/or accelerates decline of the other. CRS are common in heart failure and universally portend worsened prognosis. Despite this heavy disease burden, the appropriate diagnosis and classification of CRS remains problematic. In addition to the hemodynamic drivers of decreased renal perfusion and increased renal vein pressure, induction of the renin-angiotensin-aldosterone system, stimulation of the sympathetic nervous system, disruption of balance between nitric oxide and reactive oxygen species, and inflammation are implicated in the pathogenesis of CRS. Medical therapy of heart failure including renin-angiotensin-aldosterone system inhibition and ß-adrenergic blockade can blunt these deleterious processes. Renovascular disease can accelerate the progression of CRS. Volume overload and diuretic resistance are common and complicate the management of CRS. In heart failure and CRS being treated with diuretics, worsening creatinine is not associated with worsened outcome if clinical decongestion is achieved. Adjunctive therapy is often required in the management of volume overload in CRS, but evidence for these therapies is limited. Anemia and iron deficiency are importantly associated with CRS and might amplify decline of cardiac and renal function. End-stage cardiac and/or renal disease represents an especially poor prognosis with limited therapeutic options. Overall, worsening renal function is associated with significantly increased mortality. Despite progress in the area of CRS, there are still multiple pathophysiological and clinical aspects of CRS that need further research to eventually develop effective therapeutic options.

Elevated Inflammatory Plasma Biomarkers in Patients With Fabry Disease: A Critical Link to Heart Failure With Preserved Ejection Fraction.

Background Because systemic inflammation and endothelial dysfunction lead to heart failure with preserved ejection fraction, we characterized plasma levels of inflammatory and cardiac remodeling biomarkers in patients with Fabry disease ( FD ). Methods and Results Plasma biomarkers were studied in multicenter cohorts of patients with FD (n=68) and healthy controls (n=40). Plasma levels of the following markers of inflammation and cardiac remodeling were determined: tumor necrosis factor ( TNF ), TNF receptor 1 ( TNFR 1) and 2 ( TNFR 2), interleukin-6, matrix metalloprotease-2 ( MMP -2), MMP -8, MMP -9, galectin-1, galectin-3, B-type natriuretic peptide ( BNP ), midregional pro-atrial natriuretic peptide ( MR -pro ANP ), and globotriaosylsphingosine. Clinical profile, cardiac magnetic resonance imaging, and echocardiogram were reviewed and correlated with biomarkers. Patients with FD had elevated plasma levels of BNP , MR -pro ANP , MMP -2, MMP -9, TNF , TNFR 1, TNFR 2, interleukin-6, galectin-1, globotriaosylsphingosine, and analogues. Plasma TNFR 2, TNF , interleukin-6, MMP -2, and globotriaosylsphingosine were elevated in FD patients with left ventricular hypertrophy, whereas diastolic dysfunction correlated with higher BNP , MR -pro ANP , and MMP -2 levels. Patients with late gadolinium enhancement on cardiac magnetic resonance imaging had greater levels of BNP , MR -pro ANP , TNFR 1, TNFR 2, and MMP -2. Plasma BNP , MR -pro ANP , MMP -2, MMP -8, TNF , TNFR 1, TNFR 2, galectin-1, and galectin-3 were elevated in patients with renal dysfunction. Patients undergoing enzyme replacement therapy who have more severe disease had higher MMP -2, TNF , TNFR 1, TNFR 2, and globotriaosylsphingosine analogue levels. Conclusions Inflammatory and cardiac remodeling biomarkers are elevated in FD patients and correlate with disease progression. These features are consistent with a phenotype dominated by heart failure with preserved ejection fraction and suggest a key pathogenic role of systemic inflammation in FD .

Chloroquine-induced cardiomyopathy: a reversible cause of heart failure.

Chloroquine (CQ) and hydroxychloroquine (HCQ) are anti-rheumatic medications frequently used in the treatment of connective tissue disorders. We present the case of a 45-year-old woman with CQ-induced cardiomyopathy leading to severe heart failure. Electrocardiographic abnormalities included bifascicular block, while structural disease consisted of severe biventricular and biatrial hypertrophy. Appropriate diagnosis via endomyocardial biopsy led to cessation of CQ and subsequent dramatic improvement in symptoms and structural heart disease. Cardiac toxicity is an under-recognized adverse effect of CQ/HCQ leading to cardiomyopathy with concentric hypertrophy and conduction abnormalities, with the potential for significant morbidity and mortality. Predisposing factors for CQ/HCQ-induced cardiomyopathy have been proposed. CQ/HCQ cardiomyopathy is a phenocopy of Fabry disease, and α-galactosidase A polymorphism may account for some heterogeneity of disease presentation.