18F-FDG/13N-ammonia cardiac PET findings in ATTR cardiac amyloidosis.

18F-flurodeoxyglycose (FDG)/13N-ammonia positron emission tomography/computed tomography (PET/CT) is frequently utilized to evaluate cardiac sarcoidosis (CS) but findings can reflect other forms of myocardial inflammation or altered myocardial metabolic activity. Herein, we present five cases where cardiac PET findings suggested CS, but right ventricular endomyocardial biopsy samples revealed ATTR-type cardiac amyloidosis.

Performance of cardiac PET/CT with and without phase analysis for detection of scar in cardiac sarcoidosis: Comparison to cardiac magnetic resonance imaging.

BACKGROUND: The presence of myocardial scar in CS patients results in poor prognosis and worse outcomes. 18F-fluorodeoxyglucose (18F-FDG) PET/CT excels at visualizing inflammation but is suboptimal at detecting scar. We evaluated PET/CT sensitivity to detect scar and investigated the incremental diagnostic value of automated PET-derived data. METHODS: 176 patients who underwent cardiac magnetic resonance (CMR) and N-13 ammonia/18F-FDG cardiac PET/CT for suspected CS within 3 months were enrolled. Scar was defined as late gadolinium enhancement (LGE) on CMR without concordant 18F-FDG uptake on 18F-FDG PET/CT. Accuracy of cardiac PET/CT at detecting scar (perfusion defect without concordant 18F-FDG uptake) was assessed before and after addition of automated PET-derived data. RESULTS: Sensitivity of PET/CT for scar detection was 45.3% (specificity 88.9%). Addition of PET-derived LV volumes and function in a logistic regression model improved sensitivity to 57.0% (specificity: 80.0%, AUC 0.72). Addition of phase analysis maximum segmental onset of myocardial contraction > 61 improved AUC to 0.75, correctly relabeling 16.3% of patients as scar (net reclassification index 8.2%). CONCLUSION: Sensitivity of gated PET MPI alone for scar detection in CS is suboptimal. Adding PET-derived volumes/function and phase analysis data results in improved detection and characterization of scar.

Electrogram-guided endomyocardial biopsy yield in patients with suspected cardiac sarcoidosis and relation to outcomes.

OBJECTIVE: Endomyocardial biopsy (EMB) is a useful diagnostic tool though the yield may be limited in many myocardial diseases. Data on the diagnostic yield and prognostic significance of EMB guided by abnormal electrograms (EGM-Bx) in suspected cardiac sarcoidosis (CS) are scarce. METHODS: Seventy-nine patients (mean age: 56 ± 12 years; 61% men) with suspected CS based on clinical and imaging features underwent right or left ventricular EGM-Bx guided by electroanatomic mapping. Tissue samples were obtained from sites with abnormal EGMs and/or abnormal cardiac imaging. The diagnostic yield of EGM-Bx was evaluated in reference to histopathologic analysis. Left ventricular assist device (LVAD) and transplantation-free survival were compared between patients with positive and negative EGM-Bx for CS. RESULTS: A total of 254 samples were obtained from abnormal EGM sites, and 126 samples from normal EGM sites guided by pre-procedure imaging findings. Abnormal histopathology was noted in 65 (26%) and 10 (8%) samples from abnormal and normal EGM sites, respectively. Histopathology confirmed CS in 16 (20%) patients, while an alternative tissue diagnosis emerged in 10 (13%) patients. Abnormal EGMs at the biopsy site had sensitivity 89% and specificity 33% for a histopathologic diagnosis of CS. LVAD and transplantation-free survival were not significantly associated with the EGM-Bx result (log-rank p = .91). CONCLUSION: In patients with suspected CS, abnormal EGM-Bx has high sensitivity and low specificity for establishing a definite CS diagnosis. Consideration of substrate abnormalities apparent on preprocedural imaging as an adjunct for selection of biopsy sites may further improve EGM-Bx yield.

A Case-Control Study of Peripartum Cardiomyopathy Using the Rochester Epidemiology Project.

BACKGROUND: The incidence of peripartum cardiomyopathy (PPCM) is known through referral center databases that may be affected by referral, misclassification, and other biases. We sought to determine the community-based incidence and natural history of PPCM using the Rochester Epidemiology Project. METHODS AND RESULTS: Incident cases of PPCM occurring between January 1, 1970, and December 31, 2014, were identified in Olmsted County, Minnesota. A total of 15 PPCM cases were confirmed yielding an incidence of 20.3 cases per 100,000 live births in Olmsted County, Minnesota. Clinical information, disease characteristics, and outcomes were extracted from medical records in a 27-county region of the Rochester Epidemiology Project including Olmsted County and matched in a 1:2 ratio with pregnant women without PPCM. A total of 48 women were identified with PPCM in the expanded 27-county region. There was 1 death and no transplants over a median of 7.3 years of follow-up. Six of the 23 women with subsequent pregnancies developed recurrent PPCM, all of whom recovered. Migraine and anxiety were identified as novel possible risk factors for PPCM. CONCLUSIONS: The population-based incidence of PPCM was 20.3 cases per 100,000 live births in Olmsted County, Minnesota. Cardiovascular outcomes were generally excellent in this community cohort.

Suppressing physiologic 18-fluorodeoxyglucose uptake in patients undergoing positron emission tomography for cardiac sarcoidosis: The effect of a structured patient preparation protocol.

OBJECTIVE: Myocardial positron emission tomography (PET) to detect cardiac sarcoidosis requires adequate patient preparation; however, in many cases physiologic myocardial 18F-fluorodeoxyglucose (18F-FDG) uptake may not be adequately suppressed. We sought to evaluate the efficacy of a structured patient preparation protocol as recommended by the joint SNMMI/ASNC expert consensus document on the role of 18F-FDG PET/CT in cardiac sarcoid detection and therapy monitoring. The SNMMI/ASNC preparation protocol recommends at least two high-fat (> 35 g), low-carbohydrate (< 3 g) (HFLC) meals the day before testing followed by fasting for at least 4-12 hours. METHODS: All unique PET scans performed for cardiac sarcoidosis before (group 1) and after (group 2) application of the new preparation protocol were included in the study. In group 1, patients were given a preparation protocol of HFLC meals with suggested meals examples, while patients in group 2 received detailed diet instructions, together with accepted and non-accepted meal examples along. In group 2, reinforcement of instructions by nursing staff and review of dietary log were performed prior to testing. All PET images were evaluated for suppression of physiologic myocardial 18F-FDG uptake. RESULTS: Group 1 included 124 unique patients, and group 2 included 232 unique patients. There were no significant differences in baseline patient characteristics between the two groups. Suppression of physiologic myocardial 18F-FDG uptake was achieved in 91% of patients in group 2, compared to 78% of patients in group 1 (P < .001). A "diffuse" myocardial uptake pattern, indicating inadequate 18F-FDG suppression, was seen in 2% of studies in group 2 vs 12% in group 1 (P < .001). CONCLUSION: In this single-center study, application of a structured preparation protocol was highly successful in achieving suppression of physiologic myocardial 18F-FDG uptake in patients undergoing myocardial PET for cardiac sarcoidosis.

Diagnostic and predictive value of speckle tracking echocardiography in cardiac sarcoidosis.

BACKGROUND: Sarcoidosis is a systemic granulomatous disease that may affect the myocardium. This study evaluated the diagnostic and prognostic value of 2-dimensional speckle tracking echocardiography in cardiac sarcoidosis (CS). METHODS: Eighty-three patients with extracardiac, biopsy-proven sarcoidosis and definite/probable diagnosis of cardiac involvement diagnosed from January 2005 through December 2016 were included. Strain parameters in early stages of CS, in a subgroup of 23 CS patients with left ventricular ejection fraction (LVEF) within normal limits (LVEF> 52% for men: > 54% for women, mean value: 57.3% ± 3.8%) and no wall motion abnormalities was compared with 97 controls (1:4) without cardiac disease. LV and right ventricular (RV) global longitudinal (GLS), circumferential (GCS), and radial (GRS) strain and strain rate (SR) analyses were performed with TomTec software and correlated with cardiac outcomes (including heart failure and arrhythmias). This study was approved by the Mayo Clinic Institutional Review Board, and all patients gave informed written consent to participate. RESULTS: Mean age of CS patients was 53.6 ± 10.8 years, and 34.9% were women. Mean LVEF was 43.2% ± 12.4%; LV GLS, - 12.4% ± 3.7%; LV GCS, - 17.1% ± 6.5%; LV GRS, 29.3% ± 12.8%; and RV wall GLS, 14.6% ± 6.3%. In the 23 patients with early stage CS with normal LVEF and RV systolic function, strain parameters were significantly reduced when compared with controls (respectively: LV GLS, - 15.9% ± 2.5% vs - 18.2% ± 2.7% [P = .001]; RV GLS, - 16.9% ± 4.5% vs - 24.1% ± 4.0% [P < .001]). A LV GLS value of - 16.3% provided 82.2% sensitivity and 81.2% specificity for the diagnosis of CS (AUC 0.91), while a RV value of - 19.9% provided 88.1% sensitivity and 86.7% specificity (AUC 0.93). Hospital admission and heart failure significantly correlated to impaired LV GLS (> - 14%). CONCLUSION: Reduced strain values in the LV GLS and RV GLS can be used in the diagnostic algorithm in patients with suspicion of cardiac sarcoidosis. These values also correlate with adverse cardiovascular events.

Restrictive Cardiomyopathy: Genetics, Pathogenesis, Clinical Manifestations, Diagnosis, and Therapy.

Restrictive cardiomyopathy (RCM) is characterized by nondilated left or right ventricle with diastolic dysfunction. The restrictive cardiomyopathies are a heterogenous group of myocardial diseases that vary according to pathogenesis, clinical presentation, diagnostic evaluation and criteria, treatment, and prognosis. In this review, an overview of RCMs will be presented followed by a detailed discussion on 3 major causes of RCM, for which tailored interventions are available: cardiac amyloidosis, cardiac sarcoidosis, and cardiac hemochromatosis. Each of these 3 RCMs is challenging to diagnose, and recognition of each disease entity is frequently delayed. Clinical clues to promote recognition of cardiac amyloidosis, cardiac sarcoidosis, and cardiac hemochromatosis and imaging techniques used to facilitate diagnosis are discussed. Disease-specific therapies are reviewed. Early recognition remains a key barrier to improving survival in all RCMs.

Peripartum Cardiomyopathy: Progress in Understanding the Etiology, Management, and Prognosis.

Occurring in approximately 1 in 1000 live births in the United States, peripartum cardiomyopathy (PPCM) is characterized by left ventricular ejection fraction reduced to less than 45% near the end of pregnancy or within the first 5 months after delivery. Although the cause of PPCM remains unclear, increasing evidence supports a complex interaction of genetic and environmental factors contributing to angiogenic imbalance, which may lead to myocardial dysfunction in a susceptible woman. This article reviews the progress that has been made regarding understanding of the cause, management, and natural history of PPCM.

Peripartum Cardiomyopathy and Preeclampsia: Overlapping Diseases of Pregnancy.

PURPOSE OF REVIEW: Hypertensive disorders of pregnancy (HDP) often result in cardiac dysfunction and have been variably included as a risk factor for peripartum cardiomyopathy (PPCM). However, there is debate regarding the relationship between the two entities. RECENT FINDINGS: Diastolic dysfunction appears to be more predominant among gravidas with HDP, while systolic dysfunction predominates in PPCM. However, this finding is not consistent in all studies. Recent examinations of mortality and morbidity associated with PPCM in the setting of HDP do not demonstrate a predominant pattern with a mixture of results. Further, right ventricular dysfunction is identified to be a common theme in both populations. From a basic science perspective, there is evidence to demonstrate a predominantly anti-angiogenic milieu in both PPCM and HDP. PPCM and HDP associated cardiomyopathy overlap significantly. As such, unifying theories for their pathophysiology should be investigated.

Melatonin as a preventive and curative therapy against pulmonary hypertension.

Pulmonary hypertension (PH) is characterized by elevated pulmonary arterial pressure, which leads to right ventricular (RV) hypertrophy and failure. The pathophysiological mechanisms of PH remain unclear but oxidative stress is believed to contribute to RV dysfunction. Melatonin is a powerful antioxidant and is cardioprotective against ischemia-reperfusion injury and hypertension. Therefore, we hypothesized that a chronic treatment with melatonin, given as a curative or preventive therapy, may confer cardiovascular benefits in PH. PH was induced in Long Evans rats (n ≥ 6 per group), with a single subcutaneous injection of monocrotaline (MCT, 80 mg/kg). Melatonin was given daily in the drinking water, with the treatment starting either on the day of the injection of MCT (dose testing: melatonin 75 ng/L and 6 mg/kg), 14 days after the injection of MCT (curative treatment: 6 mg/kg), or 5 days before the injection (preventive treatment: 6 mg/kg). The development of PH was assessed by measuring RV hypertrophy, RV function, cardiac interstitial fibrosis, and plasma oxidative stress. Compared with controls, MCT-treated rats displayed RV hypertrophy and dysfunction, increased interstitial fibrosis, and elevated plasma oxidative stress. A chronic melatonin treatment (75 ng/L or 6 mg/kg) reduced RV hypertrophy, improved RV function and reduced plasma oxidative stress. Curative and preventive treatment improved RV functional and plasma oxidative stress parameters and reduced cardiac interstitial fibrosis. Our data demonstrate that melatonin confers cardioprotection in this model of PH. As melatonin is an inexpensive and safe drug, we propose that clinical investigation of the effects of melatonin on RV function in patients with PH should be considered.

Idiopathic giant cell myocarditis and cardiac sarcoidosis.

Idiopathic giant cell myocarditis (GCM) and cardiac sarcoidosis (CS) are rare disorders that cause cardiomyopathy, often with ventricular arrhythmias or heart block. Infection, autoimmune processes, and genetics have all been implicated in the pathogenesis of these diseases, but the etiology for both diseases is likely a complex multifactorial process. Both GCM and CS are generally progressive despite treatment with standard heart failure and arrhythmia therapies. Making the diagnosis of GCM or CS on initial clinical presentation is possible in only a small percentage of patients, so myocardial tissue diagnosis is required. The use of multiple noninvasive imaging modalities may aid in diagnosis and assessment of response to treatment. Establishing the diagnosis of GCM or CS early is crucial, as tailored immunosuppressive treatment may significantly alter the clinical course of these patients. The prognosis of patients with GCM is poor, while the prognosis for patients with CS varies according to degree of left ventricular dysfunction.

Sex and age differences in sST2 in cardiovascular disease.

Aims: The goal of this study was to determine whether sex and age differences exist for soluble ST2 (sST2) for several cardiovascular diseases (CVDs). Methods: We examined sST2 levels using an ELISA kit for myocarditis (n = 303), cardiomyopathy (n = 293), coronary artery disease (CAD) (n = 239), myocardial infarct (MI) (n = 159), and congestive heart failure (CHF) (n = 286) and compared them to controls that did not have CVDs (n = 234). Results: Myocarditis occurred in this study in relatively young patients around age 40 while the other CVDs occurred more often in older individuals around age 60. We observed a sex difference in sST2 by age only in myocarditis patients (men aged 38, women 46, p = 0.0002), but not for other CVDs. Sera sST2 levels were significantly elevated compared to age-matched controls for all CVDs: myocarditis (p ≤ 0.0001), cardiomyopathy (p = 0.0009), CAD (p = 0.03), MI (p = 0.034), and CHF (p < 0.0001) driven by elevated sST2 levels in females for all CVDs except myocarditis, which was elevated in both females (p = 0.002) and males (p ≤ 0.0001). Sex differences in sST2 levels were found for myocarditis and cardiomyopathy but no other CVDs and were higher in males (myocarditis p = 0.0035; cardiomyopathy p = 0.0047). sST2 levels were higher in women with myocarditis over 50 years of age compared to men (p = 0.0004) or women under 50 years of age (p = 0.015). In cardiomyopathy and MI patients, men over 50 had significantly higher levels of sST2 than women (p = 0.012 and p = 0.043, respectively) but sex and age differences were not detected in other CVDs. However, women with cardiomyopathy that experienced early menopause had higher sST2 levels than those who underwent menopause at a natural age range (p = 0.02). Conclusion: We found that sex and age differences in sera sST2 exist for myocarditis, cardiomyopathy, and MI, but were not observed in other CVDs including CAD and CHF. These initial findings in patients with self-reported CVDs indicate that more research is needed into sex and age differences in sST2 levels in individual CVDs.

Evaluation of bromocriptine in the treatment of acute severe peripartum cardiomyopathy: a proof-of-concept pilot study.

BACKGROUND: Peripartum cardiomyopathy (PPCM) is a potentially life-threatening heart disease that occurs in previously healthy women. We identified prolactin, mainly its 16-kDa angiostatic and proapoptotic form, as a key factor in PPCM pathophysiology. Previous reports suggest that bromocriptine may have beneficial effects in women with acute onset of PPCM. METHODS AND RESULTS: A prospective, single-center, randomized, open-label, proof-of-concept pilot study of women with newly diagnosed PPCM receiving standard care (PPCM-Std; n=10) versus standard care plus bromocriptine for 8 weeks (PPCM-Br, n=10) was conducted. Because mothers receiving bromocriptine could not breast-feed, the 6-month outcome of their children (n=21) was studied as a secondary end point. Blinded clinical, hemodynamic, and echocardiographic assessments were performed at baseline and 6 months after diagnosis. Cardiac magnetic resonance imaging was performed 4 to 6 weeks after diagnosis in PPCM-Br patients. There were no significant differences in baseline characteristics, including serum 16-kDa prolactin levels and cathepsin D activity, between the 2 study groups. PPCM-Br patients displayed greater recovery of left ventricular ejection fraction (27% to 58%; P=0.012) compared with PPCM-Std patients (27% to 36%) at 6 months. One patient in the PPCM-Br group died compared with 4 patients in the PPCM-Std group. Significantly fewer PPCM-Br patients (n=1, 10%) experienced the composite end point of poor outcome defined as death, New York Heart Association functional class III/IV, or left ventricular ejection fraction <35% at 6 months compared with the PPCM-Std patients (n=8, 80%; P=0.006). Cardiac magnetic resonance imaging revealed no intracavitary thrombi. Infants of mothers in both groups showed normal growth and survival. CONCLUSIONS: In this trial, the addition of bromocriptine to standard heart failure therapy appeared to improve left ventricular ejection fraction and a composite clinical outcome in women with acute severe PPCM, although the number of patients studied was small and the results cannot be considered definitive. Larger-scale multicenter and blinded studies are in progress to test this strategy more robustly.

Peripartum Cardiomyopathy.

Peripartum cardiomyopathy (PPCM) is a form of heart failure that occurs toward the end of pregnancy or in the months following pregnancy and is marked by left ventricular systolic dysfunction. The cause of PPCM remains unknown and there is no diagnostic test specific to PPCM. Outcomes vary and include complete left ventricular recovery, persistent cardiac dysfunction, transplant, and death. Numerous advances have been made in understanding this disease, but many knowledge gaps remain. This article reviews recent data and recommendations for clinical practice in addition to highlighting the multiple knowledge gaps related to PPCM that warrant further investigation.

Effect of Corticosteroid Therapy in Patients With Cardiac Sarcoidosis on Frequency of Venous Thromboembolism.

Sarcoidosis is a multisystem inflammatory condition with occasional cardiac involvement (CS), which may be associated with risk of venous thromboembolism (VTE). As data on VTE in CS are sparse and corticosteroid therapy has not been previously examined, we aim to determine the association between CS, corticosteroid treatment for CS, and VTE. Patients referred to our institution with concern for sarcoidosis and underwent a positron emission tomography (PET) scan were retrospectively assessed. Chi-squared and multivariate regression analyses were conducted to determine the association between a diagnosis of sarcoidosis, CS, corticosteroid use, and VTE events. Six hundred and forty nine patients were split into 3 categories: 235 with no sarcoidosis (NS), 91 with extra-cardiac sarcoidosis only (ECS), and 323 with CS (isolated CS and/or CS with extra cardiac sarcoid). Thirty nine CS, 7 ECS, and 9 NS patients developed PE while 44 CS, 3 ECS, and 18 NS patients developed DVT. On multivariate regression, neither CS nor ECS was an independent risk factor for VTE (p >0.05) but corticosteroid use was independently associated with VTE (HR 3.06, p = 0.007 for PE, HR 6.21, p <0.0001 for DVT). On logistic regression analysis, corticosteroid dose was found to be independently associated with both PE (p = 0.001) and DVT (p = 0.007). Optimal threshold for defining VTE risk with corticosteroid therapy was a prednisone-equivalent dose of 17.5 mg. In conclusion, contrary to previous studies, this current study found that neither sarcoidosis nor CS is an independent risk factor for VTE. Rather, corticosteroid therapy was associated with an increased risk of VTE.

Natural History of Patients Diagnosed with Cardiac Sarcoidosis at Left Ventricular Assist Device Implantation or Cardiac Transplantation.

To our knowledge, natural history has not been reported for cardiac sarcoidosis (CS) diagnosed by pathologic evaluation of the apical core at left ventricular assist device (LVAD) implantation or cardiac transplantation. We retrospectively identified 232 consecutive patients meeting CS criteria. Of these patients, 54 were diagnosed by pathologic confirmation of CS, 10 after evaluation of the apical core (LVAD implant) or explanted heart (transplant). We compared clinical characteristics at initial evaluation and outcomes for these 10 patients with those of 10 patients with known CS before LVAD implant/transplant. In the study group, five patients (50%) had confirmed extracardiac sarcoidosis before LVAD implant/transplant; five had not been diagnosed with sarcoidosis. Mean (standard deviation) left ventricular ejection fraction at initial evaluation was 23% (16%), and left ventricular end-diastolic dimension was 61 (10) mm. Four patients died during follow-up; however, no survival difference was found for the 10 patients diagnosed incidentally and the group with a previous diagnosis or institutional LVAD/transplant cohorts. Patients diagnosed with CS on pathological examination of the apical core/explanted heart may have severe dilated cardiomyopathy as the initial presentation. Outcomes for patients with CS after advanced heart failure therapies may be comparable with those of non-CS patients.

Detecting cardiomyopathies in pregnancy and the postpartum period with an electrocardiogram-based deep learning model.

AIMS: Cardiovascular disease is a major threat to maternal health, with cardiomyopathy being among the most common acquired cardiovascular diseases during pregnancy and the postpartum period. The aim of our study was to evaluate the effectiveness of an electrocardiogram (ECG)-based deep learning model in identifying cardiomyopathy during pregnancy and the postpartum period. METHODS AND RESULTS: We used an ECG-based deep learning model to detect cardiomyopathy in a cohort of women who were pregnant or in the postpartum period seen at Mayo Clinic. Model performance was evaluated using the area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, and specificity. We compared the diagnostic probabilities of the deep learning model with natriuretic peptides and a multivariable model consisting of demographic and clinical parameters. The study cohort included 1807 women; 7%, 10%, and 13% had left ventricular ejection fraction (LVEF) of 35% or less, <45%, and <50%, respectively. The ECG-based deep learning model identified cardiomyopathy with AUCs of 0.92 (LVEF ≤ 35%), 0.89 (LVEF < 45%), and 0.87 (LVEF < 50%). For LVEF of 35% or less, AUC was higher in Black (0.95) and Hispanic (0.98) women compared to White (0.91). Natriuretic peptides and the multivariable model had AUCs of 0.85 to 0.86 and 0.72, respectively. CONCLUSIONS: An ECG-based deep learning model effectively identifies cardiomyopathy during pregnancy and the postpartum period and outperforms natriuretic peptides and traditional clinical parameters with the potential to become a powerful initial screening tool for cardiomyopathy in the obstetric care setting.

Brief Communication: Immune Checkpoint Inhibitor-induced Diaphragmatic Dysfunction: A Case Series.

Diaphragmatic dysfunction is a rare cause of dyspnea that can lead to hypercapnic respiratory failure. A variety of causes of diaphragmatic dysfunction have been identified, including myopathies and neuropathies, the latter of which can be further subdivided into infectious, idiopathic, demyelinating, malignant, and iatrogenic etiologies. Now, in the era of immune checkpoint inhibitors (ICIs), case reports of immune-mediated phrenic nerve palsies have been described. This diagnosis can be challenging to make, as dyspnea is a common presenting complaint and immune-mediated palsy of the phrenic nerve is a rarely described complication of ICI therapy. At Mayo Clinic, 3 patients with diaphragmatic dysfunction in the setting of ICI therapy were successfully treated without mortality. This case series describes the presentation, diagnoses, and management of these patients and their clinical outcomes.

Global Left Ventricular Strain at Presentation Is Associated with Subsequent Recovery in Patients with Peripartum Cardiomyopathy.

BACKGROUND: Peripartum cardiomyopathy (PPCM) is a serious complication of pregnancy associated with variable degrees of left ventricular (LV) recovery. The aim of this study was to test the hypothesis that global LV strain at presentation has prognostic value in patients with PPCM. METHODS: One hundred patients with PPCM aged 30 ± 6 years were enrolled in the multicenter Investigation in Pregnancy Associated Cardiomyopathy study along with 21 normal female control subjects. Speckle-tracking global longitudinal strain (GLS) and global circumferential strain (GCS) analysis was performed. The predefined primary combined outcome variable was death, transplantation, LV assist device implantation, or evidence of persistent LV dysfunction (LV ejection fraction [LVEF] < 50%) at 1 year. RESULTS: GLS measurement was feasible in 110 subjects: 89 of 90 patients with PPCM (99%) with echocardiographic data and all 21 control subjects. Of 84 patients (94%) with 1-year follow-up, 21 (25%) had unfavorable primary outcomes: four LV assist device placements, two deaths, and 15 patients with persistent LV dysfunction. GLS at presentation with a cutoff of 10.6% (absolute value) was specifically associated with the subsequent primary outcome with 75% sensitivity and 95% specificity. GCS at presentation with a cutoff of 10.1% was associated with the primary outcome with 78% sensitivity and 84% specificity. GLS and GCS remained significantly associated with outcomes after adjusting for LVEF (GLS odds ratio, 2.07; P < .001; GCS odds ratio, 1.37; P = .005). GLS was significantly additive to LVEF (C statistic = 0.76-0.91, net reclassification improvement = 1.32, P < .001). CONCLUSIONS: GLS and GCS in patients with PPCM at presentation were associated with subsequent clinical outcomes, including death, LV assist device implantation, and evidence of persistent LV dysfunction. Strain measures may add prognostic information over LVEF for risk stratification.