Survival, ventricular arrhythmia, and implantable cardioverter-defibrillator usefulness in toxic cardiomyopathy due to substance abuse.

BACKGROUND: Toxic dilated cardiomyopathy (T-DCM) due to substance abuse is now recognized as a potential cause of severe left ventricular dysfunction. The burden of ventricular arrhythmias (VA) and the role of a prophylactic implantable cardioverter-defibrillator (ICD) are not well documented in this population. We aim to assess the usefulness of ICD implantation in a T-DCM cohort. METHODS: Patients younger than 65 years with a left ventricular ejection fraction (LVEF) < 35% followed at a tertiary center heart failure (HF) clinic between January 2003 and August 2019 were screened for inclusion. The diagnosis of T-DCM was confirmed after excluding other etiologies, and substance abuse was established according to the DSM-5 criteria. The composite primary endpoints were arrhythmic syncope, sudden cardiac death (SCD), or death of unknown cause. The secondary endpoints were the occurrence of sustained VA and/or appropriate therapies in ICD carriers. RESULTS: Thirty-eight patients were identified, and an ICD was implanted in 19 (50%) of these patients, only one for secondary prevention. The primary outcome was similar between the two groups (ICD vs. non-ICD; p = 1.00). After a mean follow-up of 33 ± 36 months, only two VA episodes were reported in the ICD group. Three patients received inappropriate ICD therapies. One ICD implantation was complicated with cardiac tamponade. Twenty-three patients (61%) had an LVEF ≥35% at 12 months. CONCLUSION: VA are infrequent in the T-DCM population. The prophylactic ICD benefit was not observed in our cohort. The ideal timing for potential prophylactic ICD implantation in this population needs further studies.

Heavy Burden of Toxic Dilated Cardiomyopathy Among Young Adults: A Retrospective Study and Review of the Literature.

BACKGROUND: Dilated cardiomyopathy (DCM) is a well described entity for heart failure (HF) with reduced left ventricular ejection fraction (LVEF). Recently, drugs and other substance of abuse have been recognised as potential triggers for DCM. The aim of this study was to assess the survival in patients ≤ 65 years of age with toxic cardiomyopathy (TCM). Left ventricular remodelling and the potential usefulness of left ventricular assist devices (LVADs) was also assessed. METHODS: This was a single-centre retrospective study from January 2003 to August 2019 of 553 patients ≤ 65 years old with LVEF < 40% at a tertiary-care cardiology centre. RESULTS: A total of 201 patients (36%) had a diagnosis of idiopathic DCM. Further analysis identified 38 patients (19%) for which a TCM was the most likely etiology (amphetamine [50%], cocaine [37%], anabolic steroids [8%], and energy drinks [5%]). Despite a mean LVEF of 17 ± 8% at presentation, most patients (n = 27; 71%) had event-free survival with guideline-directed medical therapy, and 61% (n = 23) recovered an LVEF ≥ 40% after a median follow-up of 21 ± 23 months. Seven patients (18%) required an LVAD and 1 patient (3%) a transplantation. All LVADs were explanted or decommissioned after partial or complete LVEF recovery after a median support time of 11 ± 4 months. CONCLUSIONS: TCM induced by substance abuse is a frequent cause of HF, accounting for almost 20% of patients ≤ 65 years of age with DCM of unknown etiology. Treatment must be tailored on an individual basis. Mechanical circulatory support demonstrated its usefulness in carefully selected patients.

Effect of Acute Immunosuppression on Left Ventricular Recovery and Mortality in Fulminant Viral Myocarditis: A Case Series and Review of Literature.

BACKGROUND: Fulminant viral myocarditis (FVM) is a rare cause of cardiogenic shock associated with high morbidity and mortality rates. An inappropriately activated immune system results in severe myocardial inflammation. Acute immunosuppressive therapy for FVM therefore gained in popularity and was described in numerous retrospective studies. METHODS: We conducted an extensive review of the literature and compared it with our single-centre retrospective review of all cases of FVM from 2009-2019 to evaluate the possible effect of acute immunosuppression with intravenous immunoglobulins and/or high dose corticosteroids in patients with FVM. RESULTS: We report on 17 patients with a mean age of 46 ± 15 years with a mean left ventricular ejection fraction (LVEF) of 15 ± 9% at admission. Fourteen (82%) of our patients had acute LVEF recovery to ≥ 45% after a mean time from immunosuppression of 74 ± 49 hours (3.1 days). Extracorporeal membrane oxygenation (ECMO) was required in 35% (6/17) of our patients for an average support of 126 ± 37 hours. Overall mortality was 12% (2/17). No patient needed a long-term left ventricular assist device or heart transplant. All surviving patients achieved complete long-term LVEF recovery. CONCLUSIONS: Our cohort of 17 severely ill patients received acute immunosuppressive therapy and showed a rapid LVEF recovery, short duration of ECMO support, and low mortality rate. Our suggested scheme of investigation and treatment is presented. These results bring more cases of successfully treated FVM with immunosuppression and ECMO to the literature, which might stimulate further prospective trials or a registry.

CONTEXTE: La myocardite virale fulminante (MVF) est une cause rare de choc cardiogénique, un état associé à des taux élevés de morbidité et de mortalité. L'activation inappropriée du système immunitaire entraîne une inflammation grave du myocarde. Le recours à un traitement immunosuppresseur aigu en cas de MVF a donc gagné en popularité et a fait l'objet de nombreuses études rétrospectives. MÉTHODOLOGIE: Nous avons effectué une revue exhaustive de la littérature et comparé nos observations avec les résultats de notre examen rétrospectif de tous les cas de MVF traités dans un même centre entre 2009 et 2019, afin d'évaluer l'effet possible d'une immunosuppression aiguë par des immunoglobulines administrées par voie intraveineuse et/ou par une corticothérapie à forte dose chez les patients présentant une MVF. RÉSULTATS: Nous rapportons les cas de 17 patients dont l'âge moyen était de 46 ± 15 ans et qui avaient une fraction d'éjection ventriculaire gauche (FEVG) moyenne de 15 ± 9 % à l'admission. Chez 14 (82 %) d'entre eux, la FEVG aiguë s'est rétablie à une valeur ≥ 45 % dans les 74 ± 49 heures (3,1 jours) en moyenne après l'administration d'un traitement immunosuppresseur. Un soutien par oxygénation extracorporelle par membrane (ECMO) a dû être administré à 35 % (6/17) des patients, pendant 126 ± 37 heures en moyenne. Le taux global de mortalité s'établissait à 12 % (2/17). Aucun patient n'a eu besoin d'assistance ventriculaire gauche de façon prolongée ni d'une transplantation cardiaque. La FEVG a fini par se rétablir complètement chez tous les patients qui ont survécu. CONCLUSIONS: Les 17 patients gravement malades de notre cohorte qui ont reçu un traitement immunosuppresseur aigu ont vu leur FEVG se rétablir rapidement, n'ont eu besoin d'ECMO que pendant une courte période et ont affiché un faible taux de mortalité. Nous présentons notre algorithme d'investigation et de traitement. Nos résultats s'ajoutent à ceux d'autres études témoignant de l'efficacité du traitement de la MVF par immunosuppression et ECMO, ce qui pourrait stimuler la réalisation de nouveaux essais prospectifs ou l'établissement d'un registre.

Do Energy Drinks Really Give You Wings? Left Ventricular Assist Device Therapy as a Bridge to Recovery for an Energy Drink-Induced Cardiomyopathy.

The deleterious effect of energy drinks is increasingly recognized. We present a 26-year-old woman with inotrope-dependent severe dilated cardiomyopathy, potentially caused by chronic ingestion of energy drinks. The results of extensive investigation-consisting of cardiac magnetic resonance, F-18-fluorodesoxyglucose-positron emission tomography, coronary angiography, and endomyocardial biopsy-were normal. A left ventricular assist device (LVAD) was implanted as a potential bridge to recovery. After 10 months of mechanical support and pharmacological treatment, cardiac function was recovered, and the LVAD was successfully explanted. This is the first case report of energy drink abuse leading to severe heart failure requiring mechanical support for recovery.

Giant Left Atrial Appendage Aneurysm Mimicking Mediastinal Mass and Associated with Incessant Atrial Arrhythmias.

Left atrial appendage aneurysm (LAAA) is a rare entity. Clinical manifestations include arrhythmias and systemic embolization. We show here an example of a large and ectopic LAAA mimicking a mediastinal mass on chest X-ray and presenting with incessant atrial arrhythmias. Subsequent investigations leading to the correct diagnosis are described.

Effects of chronic sildenafil use on pulmonary hemodynamics and clinical outcomes in heart transplantation.

BACKGROUND: Elevated pulmonary vascular resistance (PVR) in heart transplant (HT) candidates is associated with poor survival after HT. This study assessed the effect of peri-operative sildenafil administration on pulmonary hemodynamics and clinical outcomes in patients with advanced heart failure who were considered high-risk for HT because of elevated PVR and transpulmonary gradient (TPG). METHODS: The study included 119 consecutive patients who underwent HT between 2004 and 2011. Fifteen patients (Group A) had severe pulmonary hypertension (PH), defined as mean pulmonary pressure (MPAP)>25 mm Hg and PVR>2.5 Wood units (WU), and/or TPG>12 mm Hg after vasodilator test or the continuous administration of inotropics drugs, and 104 patients (Group B) were without severe PH. Group A received sildenafil therapy. Pulmonary hemodynamics were evaluated before HT with and without sildenafil therapy. Right catheterization was performed early after HT with sildenafil therapy and late after HT without sildenafil. Survival after HT was compared between the groups. RESULTS: The sildenafil dosage was 109±42 mg/day during 163±116 days before HT. After sildenafil therapy MPAP, PVR, and TPG decreased from 43.9±12.5 to 33.4±5.8 mm Hg, 5.0±1.1 to 3.0±1.6 WU, and 17.3±3.2 to 10.2±4.1 mm Hg, respectively (p<.01). All patients underwent successful HT. Sildenafil dosage was 140±70 mg/day for 43±45 days after HT. There were no differences in PVR and TPG with sildenafil therapy early after HT and without sildenafil 6 months after HT. Survival after HT was similar between the groups. CONCLUSION: Sildenafil therapy before and after HT in patients with severe PH is associated with improved pulmonary hemodynamics and successful HT, without an increase in post-HT mortality.

Usefulness and limitations of rituximab in managing patients with lymphoproliferative disorder after heart transplantation.

Posttransplant lymphoproliferative disorders remain an uncommon complication of heart transplant with a high mortality rate reported after conventional therapies. Four patients with posttransplant lymphoproliferative disorders, of whom 3 were CD20 positive, received intravenous dosages of rituximab, 375 mg/m(2), weekly, for 6 ± 2 weeks. The overall response rate was 75% with 3 complete responses (CD20 positive) and 1 case of progressive disease (CD20 negative). Rituximab should be considered as a first-line therapy for patients with CD20 positive posttransplant lymphoproliferative disorders.

Abrogation of ICOS/ICOS ligand costimulation in NOD mice results in autoimmune deviation toward the neuromuscular system.

NOD mice spontaneously develop insulin-dependent diabetes around 10-40 wk of age. Numerous immune gene variants contribute to the autoimmune process. However, genes that direct the autoimmune response toward ß cells remain ill defined. In this study, we provide evidence that the Icos and Icosl genes contribute to the diabetes process. Protection from diabetes in ICOS(-/-) and ICOSL(-/-) NOD mice was unexpectedly associated with the development of an autoimmune disorder of the neuro-muscular system, characterized by myositis, sensory ganglionitis and, to a reduced extent, inflammatory infiltrates in the CNS. This syndrome was reproduced upon adoptive transfer of CD4(+) and CD8(+) T cells from diseased donors to naïve NOD.scid recipients. Our data further show that protection from diabetes results from defective activation of autoimmune diabetogenic effector T cells in ICOS(-/-) NOD mice, whereas acceleration of diabetes in BDC2.5 ICOS(-/-) NOD mice is induced by a dominant defect in Treg. Taken together, our findings indicate that costimulation signals play a key role in regulating immune tolerance in peripheral tissues and that the ICOS/ICOSL costimulatory pathway influences the balance between Treg and diabetogenic effector T cells.