Search

We report a case of a woman with arrhythmogenic right ventricular cardiomyopathy (ARVC) who presented with severe right-sided heart failure and cardiac cirrhosis that mandated heart-liver transplantation. This case highlights an emerging sex-based difference in ARVC where female sex is associated with a higher risk of heart failure than in male patients with ARVC. (Level of Difficulty: Advanced.), Graphical abstract, We report a case of a woman with arrhythmogenic right ventricular cardiomyopathy (ARVC) who presented with severe right-sided heart failure…

Heart failure is an increasingly recognized later stage manifestation of arrhythmogenic right ventricular cardiomyopathy (ARVC) that can require heart transplantation (HT) to appropriately treat. We aimed to study contemporary ARVC HT outcomes in a national registry.The United Network for Organ Sharing registry was queried for HT recipients from 1/1994 through 2/2020. ARVC patients were compared with non-ARVC dilated, restrictive, and hypertrophic cardiomyopathy HT patients (HT for ischaemic and valvular disease was excluded from analysis). Post-HT survival was assessed using Kaplan-Meier estimates. A total of 189 of 252 (75%) waitlisted ARVC patients (median age 48 years, 65% male) underwent HT, representing 0.3% of the total 65 559 HT during the study time period. Annual frequency of HT for ARVC increased significantly over time. ARVC patients had less diabetes (5% vs. 17%, P 0.001), less cigarette use (15% vs. 23%, P 0.001), lower pulmonary artery and pulmonary capillary wedge pressures, and lower cardiac output than the 33 659 non-ARVC patients (P 0.001). Ventricular assist device use was significantly lower in ARVC patients (8% vs. 32%, P 0.001); 1 and 5 year post-HT survival was 97% and 93% for ARVC vs. 95% and 82% for non-ARVC HT recipients (P 0.001). On adjusted multivariable Cox regression, ARVC had decreased risk of post-HT death compared with non-ARVC aetiologies (hazard ratio 0.48, 95% confidence interval 0.28-0.82, P = 0.008). Patients with ARVC also had lower risk of death or graft failure than non-ARVC patients (hazard ratio 0.51, 95% confidence interval 0.32-0.81, P = 0.004).In the largest series of HT in ARVC, we found that HT is increasingly performed in ARVC, with higher survival compared with other cardiomyopathy aetiologies. The right ventricular predominant pathophysiology may require unique considerations for heart failure management, including HT.

BACKGROUND: The role of checkpoint axes in transplantation has been partially addressed in animal models, but not in humans. Occurrence of fulminant myocarditis with allo-rejection-like immunologic features in patients under anti-PD-1 treatment suggests a key role of the PD1/PD-L1 axis in cardiac immune homeostasis. METHODS: We cross-sectionally studied 23 heart transplant patients undergoing surveillance endomyocardial biopsy. Endomyocardial tissue and peripheral blood mononuclear cells were analyzed by flow cytometry. Multivariate logistic regression analyses including demographic, clinical and hemodynamic parameters were performed. Murine models were used to evaluate the impact of PD-L1 endothelial graft expression in allo-rejection. RESULTS: We found that myeloid cells dominate the composition of the graft leukocyte compartment in most patients, with variable T cell frequencies. The CD4:CD8 T cell ratios were between 0 and 1.5. The proportion of PD-L1 expressing cells in graft endothelial cells, fibroblasts and myeloid leukocytes ranged from negligible up to 60%. We found a significant inverse logarithmic correlation between the proportion of PD-L1(+)HLA-DR(+) endothelial cells and CD8(+) T cells (slope −18.3, 95% CI −35.3/−1.3, P=0.030). PD-L1 expression and leukocyte patterns were independent of demographic, clinical and hemodynamic parameters. We confirmed the importance of endothelial PD-L1 expression in a murine allogeneic heart transplantation model, in which Tie2(Cre)pdl1(fl/fl) grafts lacking PD-L1 in endothelial cells were rejected significantly faster than controls. CONCLUSIONS: Loss of graft endothelial PD-L1 expression may play a role in regulating CD8(+) T cell infiltration in human heart transplantation. Murine model results suggest that loss of graft endothelial PD-L1 may facilitate allo-responses and rejection.

The 2017 focused update of the 2013 ACC/AHA guideline on heart failure contains new and important recommendations on prevention, novel biomarker uses, heart failure with preserved ejection fraction (HFpEF), and comorbidities such as hypertension, iron deficiency, and sleep-disordered breathing. Potential implications for management of acute decompensated heart failure will also be explored.

Introduction Left ventricular assist device (LVAD) core pathology may provide definitive cardiomyopathy etiology and guide management. We present a case of progressive cardiomyopathy concerning for myocarditis in a patient with cutaneous T cell lymphoma (CTCL) undergoing LVAD implantation. Case Report A 63-year-old man presented with mildly reduced left ventricular ejection fraction (LVEF) and ventricular tachycardia (VT). He had an extensive history of Gulf War Syndrome, heavy metal exposure, chronic kidney disease, hypercalcemia and cutaneous T cell lymphoma, managed with ultraviolet light therapy and methotrexate. Cardiac magnetic resonance (CMR) imaging demonstrated anteroseptal and inferolateral wall delayed gadolinium enhancement (DGE). Coronary angiography showed no coronary artery disease. Fluorodeoxyglucose-positron emission tomography (FDG-PET) showed reduced lateral and inferior wall perfusion but no myocardial FDG uptake or evidence of systemic CTCL. Endomyocardial biopsy demonstrated mild hypertrophy and marked interstitial fibrosis, however no evidence of sarcoidosis or myocarditis. Over the next 2 years, his cardiomyopathy progressed (LVEF 15-20%, LVDd 7.2cm). Upon readmission for VT and heart failure (HF), repeat FDG-PET showed myocardial FDG uptake - perfusion mismatch pattern prompting oral prednisone initiation. Durable LVAD was implanted 5 days later given clinical progression. LVAD core pathology showed myocardial T cell infiltration with a clonal T cell gene rearrangement (Figure 1). Peripheral blood and PET markers remained otherwise negative for CTCL. After LVAD, his HF and VT stabilized, and he is undergoing treatment plan for systemic T cell lymphoproliferative disorder. Summary We present a case of myocardial T cell lymphoproliferative disorder presenting as progressive cardiomyopathy and highlight the role of LVAD core pathology in diagnosis.

The pulse amplitude ratio, the ratio of pulse pressure at the end of a Valsalva maneuver to before the onset of Valsalva, correlates with filling pressure. This study aimed to noninvasively estimate cardiac filling pressure in patients with heart failure. We developed a noninvasive handheld device to measure pulse amplitude ratio using finger photoplethysmography. In 69 patients who underwent right heart catheterization, photoplethysmography waveforms were recorded during a standardized Valsalva maneuver, and in 60 of these patients, pulse amplitude ratio was able to be calculated. Pulse amplitude ratio correlated with pulmonary capillary wedge pressure (PCWP) (r = 0.58, p 15 mm Hg was statistically significant (p 15 mm Hg with 73% sensitivity and 77% specificity. Pulse amplitude ratio also increased by an average of 0.03 with a leg raise maneuver (p = 0.05, n = 36). In conclusion, we demonstrate that noninvasively measured response to the Valsalva maneuver in patients with HF can estimate PCWP and also detect changes within a single patient.

Background Among various cardiac autoantibodies (AAbs), those recognizing the β 1 -adrenergic receptor (β 1 AR) demonstrate agonist-like effects and induce myocardial damage that can be reversed by β-blockers and immunoglobulin G3 (IgG3) immunoadsorption. Objectives The goal of this study was to investigate the role of β 1 AR-AAbs belonging to the IgG3 subclass in patients with recent-onset cardiomyopathy. Methods Peripheral blood samples were drawn at enrollment in patients with recent-onset cardiomyopathy (left ventricular ejection fraction [LVEF] ≤0.40; 1 AR-AAb was determined, and echocardiograms were assessed, at baseline and 6 months. Patients were followed up for ≤48 months. Results Among the 353 patients who had blood samples adequate for the analysis, 62 (18%) were positive for IgG3-β 1 AR-AAbs (IgG3 group), 58 (16%) were positive for IgG but not IgG3 (non-IgG3 group), and the remaining were negative. There were no significant differences in baseline systolic blood pressure, heart rate, or LVEF among the groups at baseline. Left ventricular end-diastolic and end-systolic diameters were significantly larger in the non-IgG3 group compared with the other groups (left ventricular end-diastolic diameter, p 1 AR-AAb was an independent predictor of LVEF at 6 months and change in LVEF over 6 months, even after multivariable adjustment (LVEF at 6 months, β = 0.20, p = 0.01; change in LVEF, β = 0.20, p = 0.008). In patients with high New York Heart Association functional class (III or IV) at baseline, the IgG3 group had a lower incidence of the composite endpoint of all-cause death, cardiac transplantation, and hospitalization due to heart failure, whereas the non-IgG3 group had the highest incidence of the composite endpoint. Conclusions IgG3-β 1 AR-AAbs were associated with more favorable myocardial recovery in patients with recent-onset cardiomyopathy.

Background/objectivesThere is limited information on the prognosis of stress cardiomyopathy (SCM) after hospital discharge. The aim of this retrospective cohort study was to determine the post-discharge prognosis of women with SCM compared to female controls with ST-segment elevation myocardial infarction (STEMI).MethodsSCM cases were identified through chart reviews of women hospitalized at a single tertiary care medical center between 2002 and 2012. Controls were randomly selected (2:1 ratio) among women admitted with a validated diagnosis of STEMI during the same period. The primary outcome was a composite of cardiovascular readmissions and death from any cause. Risk of the composite outcome was estimated from multivariate Cox proportional hazard regression models.ResultsOver an average follow-up of 24months, incidence rates of the composite outcome were 140/1000person-years among cases (n=50) and 347/1000person-years among controls (n=100; P

Background— Acute hospitalized heart failure (AHHF) is associated with 40% to 50% risk of death or rehospitalization within 6 months after discharge. Timely (before hospital discharge) risk stratification of patients with AHHF is crucial. We hypothesized that mechanical alternans (MA) and T-wave alternans (TWA) are associated with postdischarge outcomes in patients with AHHF. Methods and Results— A prospective cohort study was conducted in the intensive cardiac care unit and enrolled 133 patients (59.6±15.7 years; 65% men) admitted with AHHF. Surface ECG and peripheral arterial blood pressure waveform via arterial line were recorded continuously during the intensive cardiac care unit stay. MA and TWA were measured by enhanced modified moving average method. All-cause death or heart transplant served as a combined primary end point. MA was observed in 28 patients (25%), whereas TWA was detected in 33 patients (33%). If present, MA was tightly coupled with TWA. Mean TWA amplitude was larger in patients with both TWA and MA when compared with patients with lone TWA (median, 37 [interquartile range, 26–61] versus 22 [21–23] μV; P =0.045). After a median of 10-month postdischarge, 42 (38%) patients died and 2 had heart transplants. MA was associated with the primary end point in univariable Cox model (hazard ratio, 1.84; 95% confidence interval, 1.00–3.40; P =0.05) and after adjustment for left ventricular ejection fraction, New York Heart Association HF class, and implanted implantable cardioverter defibrillator/cardiac resynchronization therapy defibrillator (hazard ratio, 2.12 95% confidence interval, 1.13–3.98; P =0.020). TWA without consideration of simultaneous MA was not significantly associated with primary end point (hazard ratio, 1.42; 95% confidence interval, 0.77–2.64; P =0.260). Conclusions— MA is independently associated with outcomes in AHHF. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT01557465.

Takotsubo syndrome is a unique clinical condition of acute heart failure and reversible left ventricular dysfunction frequently precipitated by sudden emotional or physical stress. There is growing evidence that exaggerated sympathetic stimulation is central to the pathogenesis of this syndrome. Precisely how catecholamines mediate myocardial stunning in takotsubo syndrome remains incompletely understood; but possible mechanisms include epicardial spasm, microvascular dysfunction, direct adrenergic-receptor-mediated myocyte injury, and systemic vascular effects that alter ventricular-arterial coupling. Risk factors that increase sympathetic tone and/or catecholamine sensitivity may render individuals particularly susceptible to takotsubo syndrome during episodes of acute stress.

Background Recent studies have suggested a high prevalence of cardiac amyloidosis (CAm) in heart failure (HF) patients. CAm might be underdiagnosed owing to low clinical suspicion. Methods and Results We performed retrospective analysis of 259 patients with HF and ejection fraction (EF) ≥50% referred for endomyocardial biopsy. Seventy-three (28%) had CAm. Multivariable independent predictors of CAm were identified. Over a mean follow-up of 2.6 ± 3.3 years, CAm patients had worse survival than those without (1.5 y vs 6.3 y; log rank P Conclusions Clinicians should be suspicious of CAm in patients with EF 50%–75%, >50 years of age, BMI

During the past few years, a novel syndrome of heart failure and transient left ventricular systolic dysfunction precipitated by acute emotional or physical stress has been described. While patients with "stress cardiomyopathy"(SCM) typically present with signs and symptoms that resemble an acute coronary syndrome, it has become clear that this syndrome has unique clinical features that can readily be distinguished from acute infarction.In particular, in contrast to the irreversible myocardial injury seen with infarction, the myocardial dysfunction of SCM is completely reversible and occurs in the absence of plaque rupture and coronary thrombosis. There is increasing evidence that exaggerated sympathetic stimulation may play a pathogenic role in the development of SCM. Plasma catecholamine levels have been found to be markedly elevated in some patients with SCM, and the syndrome has been observed in other clinical states of catecholamine excess such as central neurologic injury and pheochromocytoma.Further, intravenous catecholamines can precipitate SCM in humans and can reproduce the syndrome in animal models. The precise mechanism in which excessive sympathetic stimulation may result in transient left ventricular dysfunction remains controversial. Abnormal myocardial blood flow due to sympathetically mediated microvascular dysfunction has been suggested and is supported by decreased coronary flow reserve during the acute phase of this syndrome. An alternative explanation is the direct effect of catecholamines on cardiac myocytes, possibly through cyclic AMP-mediated calcium overload. This manuscript will review the clinical and diagnostic features of SCM and will summarize the evidence supporting a sympathetically mediated pathogenesis. Clinical risk factors that appear to increase susceptibility to SCM, possibly by modulating myocyte and microvascular sensitivity to catecholamines, will also be highlighted.

Background Heart transplantation is the only definitive therapeutic intervention for end-stage heart failure. The complex mechanisms regulating the alloresponse are not entirely understood. PD-L1 is a co-inhibitory molecule able to induce T cell anergy. We hypothesize that endothelial PD-L1 modulates alloresponses in heart transplantation. Methods Using multiparameter flow cytometry we characterized stromal cells and leukocytes in endomyocardial biopsies (EMB) and peripheral blood of patients post orthotopic heart transplantation (n=21) ISHLT grade 0-1R. Controls were autopsy specimens without cardiac pathologies. Results Most of the patients (n=17) had decreased endothelial PD-L1 expression as compared to controls, 2 patients had preserved endothelial PD-L1, and 2 had over-expression. PD-L1 expression was independent of the time from transplant, immunosuppressive regimen and concentration of calcineurin inhibitor. The percentage of infiltrating CD8 + lymphocytes had an inverse exponential correlation with endothelial PD-L1 expression (r 2 =0.64, Fig 1A). We categorized patients in 2 groups: those with previous ISHLT grade 2R cellular rejection (n=10) and those with stable 0-1R scores since transplantation. A Receiver Operating Characteristic (ROC) analysis showed that the proportion of PD-L1 + endothelial cells could significantly detect history of 2R rejection, as ≤16.25% PD-L1 + endothelial cells retrospectively discriminated patients with history of 2R rejection episodes with 90% sensitivity, 78% specificity and 3.3 likelihood ratio (Fig 1B). Furthermore, the proportion of exhausted CD8 T cells in peripheral blood (CD45RA neg PD1 + ) was proportional to heart endothelial PD-L1 expression (p 2 =0.45) and inverse exponentially correlated with graft infiltrating CD8 T cells (r 2 =0.52). Conclusions Critical loss of graft endothelial PD-L1 is strongly associated with history of moderate-severe acute rejection episodes. These findings suggest that endothelial PD-L1 and its peripheral correlate, exhausted CD8 T cells, might become a useful biomarker in heart transplantation that could allow profiling of patients and personalize therapeutic and follow-up strategies.

Background B-type natriuretic peptide (BNP) correlates with cardiac filling pressures and outcomes in patients with heart failure. In heart transplant recipients, we hypothesize that a within-individual change in BNP over time would be more helpful than absolute BNP in detecting International Society of Heart and Lung Transplantation (ISHLT) grade 2R or greater rejection. Methods N-terminal pro-BNP (NT-proBNP) levels were measured in 146 consecutive transplant recipients undergoing routine endomyocardial biopsies. In the cross-sectional analysis, multiple observations per individual were accounted for using generalized estimation equations. Results A cross-sectional analysis demonstrated a weak association between NT-proBNP levels and rejection, with an odds ratio (OR) of 1.01 for every 100-pg/mL increase in NT-proBNP ( p = 0.02). However, with a doubling of an individual's NT-proBNP level, the OR for significant rejection was 2.9 (95% confidence interval [CI] 1.2–7.0), the OR with a 5-fold increase was 9.1 (95% CI, 2.7–31.5), and the OR with a 10-fold increase was 27.7 (95% CI, 5.9–129). A 10-fold increase in NT-proBNP offered a negative predictive value of 95% for the diagnosis of rejection. The relationship between within-individual increases in NT-proBNP and rejection persisted after adjusting for a fall in ejection fraction and a rise pulmonary capillary wedge pressure, and was a stronger predictor than changes in these parameters. Conclusions There is a strong, graded relationship between the within-individual increase in NT-proBNP and the odds of significant rejection independent of hemodynamic parameters. These results suggest that the change in NT-proBNP rather than absolute BNP levels may offer a non-invasive approach to detect rejection.

Background— Pulmonary hypertension (PH) secondary to left heart failure portends a poor prognosis and is a relative contraindication to heart transplantation at many centers. We tested the hypothesis that when PH persists after adequate left ventricle unloading via recent left ventricular assist device (LVAD) therapy, phosphodiesterase type 5A inhibition would decrease PH in this population. Methods and Results— We performed an open-label clinical trial using control patients not receiving therapy. Between 1999 and 2007, 138 consecutive patients undergoing cardiac transplantation evaluation with advanced left ventricular dysfunction, an elevated pulmonary capillary wedge pressure, and PH (defined by a pulmonary vascular resistance (PVR) >3 Woods Units), were treated with LVAD therapy. Fifty-eight of these patients reduced their pulmonary capillary wedge pressure to a value P P Conclusions— In patients with persistent PH after recent LVAD placement, phosphodiesterase type 5A inhibition in this open-label trial resulted in a significant decrease in PVR when compared with control patients.

Little is known about symptoms and their burden in outpatients with chronic heart failure. Diverse symptoms may be associated with poor heart failure-related quality of life, and depression may be related to increased symptoms.The number of symptoms and symptom distress (physical symptoms on the Memorial Symptom Assessment Scale-Short Form), depression (Geriatric Depression Scale-Short Form), and heart failure-related quality of life (Kansas City Cardiomyopathy Questionnaire) were measured cross-sectionally in 60 patients with heart failure from two outpatient cardiology clinics. Patients experienced a mean of nine symptoms in the previous week. More than half reported shortness of breath, lack of energy, pain, feeling drowsy, or dry mouth. In unadjusted analyses, more severe depression was associated with a greater number of symptoms (r = 0.51, P.0001) and greater overall symptom distress (r = 0.58, P.0001). For each additional depression symptom, the number of symptoms reported increased by 0.6 after adjustment for age, race, and N-terminal pro-brain natriuretic peptide (P = .01). The number of symptoms accounted for 32% of the variance in quality of life (P.0001).Patients with heart failure report a large number of distressing symptoms. Depression in patients with heart failure is associated with a greater number of symptoms, which in turn is associated with a decrease in heart failure-related quality of life. Treatment of depression and the diverse symptoms reported by patients with heart failure might significantly improve quality of life.

Background In patients with chronic heart failure, depression is common and associated with poor quality of life, more frequent hospitalizations, and higher mortality. Spiritual well-being is an important, modifiable coping resource in patients with terminal cancer and is associated with less depression, but little is known about the role of spiritual well-being in patients with heart failure. Objective To identify the relationship between spiritual well-being and depression in patients with heart failure. Design Cross-sectional study. Participants Sixty patients aged 60 years or older with New York Heart Association class II–IV heart failure. Measurements Spiritual well-being was measured using the total scale and 2 subscales (meaning/peace, faith) of the Functional Assessment of Chronic Illness Therapy—Spiritual Well-being scale, depression using the Geriatric Depression Scale—Short Form (GDS-SF). Results The median age of participants was 75 years. Nineteen participants (32%) had clinically significant depression (GDS-SF > 4). Greater spiritual well-being was strongly inversely correlated with depression (Spearman’s correlation −0.55, 95% confidence interval −0.70 to −0.35). In particular, greater meaning/peace was strongly associated with less depression (r = −.60, P

Introduction: Pulse amplitude ratio (PAR) (ratio of pulse pressure at end of Valsalva maneuver (VM) to before onset) correlates with filling pressure. We developed a noninvasive device to measure PAR using finger photoplethysmography (PPG). Hypothesis: PAR reflects PCWP in heart failure (HF) patients and can detect a change in volume status. Methods: Patients referred for right heart catheterization (RHC) or admitted for HF performed three 10-second trials of a standardized VM (at 20 mmH measured via a pressure transducer) while PPG waveforms were recorded. Results: Amongst 60 patients undergoing RHC (Table 1), PAR correlated with PCWP (Pearson correlation coefficient = 0.53, p Conclusions: We demonstrate that the response of a finger PPG waveform to a standardized VM in HF patients can estimate PCWP and also detect changes after diuresis. The ability to detect elevated filling pressures noninvasively prior to development of symptomatic congestion could reduce HF hospitalizations.

Takotsubo cardiomyopathy (TTC) is a recently described syndrome of heart failure and transient left ventricular dysfunction that is frequently precipitated by acute emotional or physical stress. Because patients with TTC typically present with chest pain, electrocardiographic abnormalities, elevated cardiac enzymes, and focal ventricular wall motion abnormalities, it is not surprising that they are often mistakenly diagnosed with acute myocardial infarction. As familiarity with TTC has increased, however, it has become clear that this syndrome not only has unique clinical features that can readily be distinguished from those of acute infarction, it also appears to have a distinct pathophysiology. In contrast to the irreversible myocardial injury seen with acute infarction, TTC is characterized by myocardial dysfunction that is transient and completely reversible and occurs in the absence of plaque rupture and coronary thrombosis. There is evidence that the myocardial stunning of TTC may be sympathetically mediated, but the precise pathogenesis of this disorder remains incompletely understood.

Background: Left ventricular assist device (LVAD) support as bridge to recovery (BTR) is uncommon for subjects with chronic heart failure. Myocardial recovery is more evident in recent onset nonischemic cardiomyopathy (ROCM); however, the prevalence of BTR in this subset has not been addressed. Methods and Results: We examined the use of LVAD support for subjects with ROCM in the Intervention in Myocarditis and Acute Cardiomyopathy 2 (IMAC2) study. The overall cohort (n 5 373) was 38% female, 21% black, with a mean age of 45 6 14 years. LVAD support was used in 3.8% (n 5 14, 43% female, age 32 6 10). Of LVAD subjects, 57% (8/14) were BTR, including 73% (8/11) of subjects with symptoms #4 months at the time of support. Left ventricular end-diastolic diameter (LVEDD) was smaller in BTR than nonrecovered (NR) subjects (P 5 .04). Myocardial inflammation was more common in BTR (75% versus 0%, P 5 .005), whereas fibrosis was less evident (25% versus 100%, P 5 .005). Of BTR subjects, 7/8 (87.5%) were alive and free of transplant with median follow-up of 19 months. Conclusion: In a multicenter registry of ROCM, BTR was common and occurred in the majority of subjects requiring LVAD support. Histology and LVEDD may assist in predicting potential for BTR in ROCM. (J Cardiac Fail 2012;18:755e761)

Background Whether myocardial recovery occurs more frequently in peripartum cardiomyopathy (PPCM) than in recent onset cardiomyopathies in men and nonperipartum women has not been prospectively evaluated. This was examined through an analysis of outcomes in the Intervention in Myocarditis and Acute Cardiomyopathy 2 (IMAC2) registry. Methods and Results IMAC2 enrolled 373 subjects with recent onset nonischemic dilated cardiomyopathy. Left ventricular ejection fraction (LVEF) was assessed at entry and 6 months, and subjects followed for up to 4 years. Myocardial recovery was compared between men (group 1), nonperipartum women (group 2) and subjects with PPCM (group 3). The cohort included 230 subjects in group 1, 104 in group 2, and 39 in group 3. The mean LVEF at baseline in groups 1, 2, and 3 was 0.23 ± 0.08, 0.24 ± 0.08, and 0.27 ± 0.07 ( P = .04), and at 6 months was 0.39 ± 0.12, 0.42 ± 0.11, and 0.45 ± 0.14 ( P = .007). Subjects in group 3 had a much greater likelihood of achieving an LVEF >0.50 at 6 months than groups 1 or 2 (19 %, 34%, and 48% respectively, P = .002). Conclusions Prospective evaluation confirms myocardial recovery is greatest in women with PPCM, poorest in men, and intermediate in nonperipartum women. On contemporary therapy, nearly half of women with PPCM normalize cardiac function by 6 months.

Aims We sought to test the hypothesis that inherent biological factors contribute to gender differences in disease pathophysiology of new-onset heart failure (HF), which can be detected from the transcriptome of a single endomyocardial biopsy (EMB). Methods and results We analysed samples from male ( n = 29) and female patients ( n = 14) with idiopathic dilated cardiomyopathy (IDCM) and new-onset HF with U133 Plus 2.0 microarrays (Affymetrix) and significance analysis of microarrays (SAM). There were 35 overexpressed and 16 downregulated transcripts in men vs. women [ q 1.2]. In addition to overexpression of Y-chromosome-related transcripts ( n = 18), such as USP9Y (FC > 13.1), DDX3Y (FC > 11.3), RPS4Y1 (FC > 9.9), and EIF1AY (FC > 11.8) in males, there was overexpression of CD24 (FC > 5.6) and KCNK1 (FC > 1.5). In females, XIST was highly overexpressed (FC > 28.9), together with X-linked zinc finger proteins (FC > 1.9) and autosomal genes GATAD1 (FC > 1.6), SLC2A12 (FC > 2.9), and PDE6B (FC > 1.5). Analysis of a public data set of end-stage IDCM ( n = 15) resulted in ∼85% overlap with our findings. Conclusion This is the first study that identified gender-specific transcriptomic differences in new-onset HF. Our findings may offer novel insights into fundamental biological differences in the pathophysiology of HF between sexes and provide a platform for personalized medicine.

A unique syndrome of heart failure and transient left ventricular systolic dysfunction precipitated by acute emotional or physical stress has recently emerged in the medical literature. The syndrome is referred to by several names, including stress cardiomyopathy, takotsubo cardiomyopathy, left ventricular apical ballooning syndrome, and broken heart syndrome. Because most patients with stress cardiomyopathy present with chest pain, electrocardiographic abnormalities, elevated cardiac enzymes, and focal left ventricular wall motion abnormalities, it is not surprising that for years this syndrome went relatively unrecognized because physicians mistook it for acute myocardial infarction. As reports of this condition have increased worldwide during the past 5 years, it has become clear that stress cardiomyopathy has unique clinical features that can be readily distinguished from those of an acute myocardial infarction. This article reviews the clinical features of stress cardiomyopathy and discusses potential pathophysiologic mechanisms of this disorder.

Background— Prediction of prognosis remains a major unmet need in new-onset heart failure (HF). Although several clinical tests are in use, none accurately distinguish between patients with poor versus excellent survival. We hypothesized that a transcriptomic signature, generated from a single endomyocardial biopsy, could serve as a novel prognostic biomarker in HF. Methods and Results— Endomyocardial biopsy samples and clinical data were collected from all patients presenting with new-onset HF from 1997 to 2006. Among a total of 350 endomyocardial biopsy samples, 180 were identified as idiopathic dilated cardiomyopathy. Patients with phenotypic extremes in survival were selected: good prognosis (event-free survival for at least 5 years; n=25) and poor prognosis (events [death, requirement for left ventricular assist device, or cardiac transplant] within the first 2 years of presentation with HF symptoms; n=18). We used human U133 Plus 2.0 microarrays (Affymetrix) and analyzed the data with significance analysis of microarrays and prediction analysis of microarrays. We identified 46 overexpressed genes in patients with good versus poor prognosis, of which 45 genes were selected by prediction analysis of microarrays for prediction of prognosis in a train set (n=29) with subsequent validation in test sets (n=14 each). The biomarker performed with 74% sensitivity (95% CI 69% to 79%) and 90% specificity (95% CI 87% to 93%) after 50 random partitions. Conclusions— These findings suggest the potential of transcriptomic biomarkers to predict prognosis in patients with new-onset HF from a single endomyocardial biopsy sample. In addition, our findings offer potential novel therapeutic targets for HF and cardiomyopathy.

Heart failure is a leading cause of mortality in the USA and Europe, and the ability to predict prognosis is essential for optimal allocation of treatments. Biomarkers offering prognostic information in patients with heart failure have recently entered practice. Although B-type natriuretic peptide (BNP) is an established biomarker,1 uric acid may also have prognostic value.2,3 Increases in BNP results primarily from increasing cardiac filling pressures, whereas increases in uric acid are associated with increased vascular tone4 and depressed myocardial contractility via increased xanthine oxidase activity.5 Thus, uric acid, like BNP, could be associated with haemodynamic compromise in heart failure. We tested the hypothesis that increased uric acid levels are associated with worsening haemodynamic compromise in patients with heart failure independent of BNP. Study patients were referred for right heart catheterisation between 1 January 2003 and 1 July 2004. Right atrial, pulmonary arterial and pulmonary capillary wedge (PCW) pressures were measured using a balloon-tipped, flow-directed catheter. Cardiac output was determined by thermodilution. Heart transplant recipients or patients currently receiving synthetic human BNP were excluded. Uric acid and N-terminal proBNP (NT-proBNP) levels were drawn during the right heart catheterisation. The study was approved by the Johns Hopkins Institutional Review Board. Patients were divided into groups on the basis of the median serum uric acid and NT-proBNP levels: low uric acid and low NT-proBNP (n = 27), high uric acid and low NT-proBNP (n = 24), low uric acid and high NT-proBNP (n = 22), and high uric acid and high NT-proBNP (n = 33). We compared haemodynamic parameters between groups using linear …

Background T-wave alternans (TWA) and mechanical alternans (MA) can be coupled. The goal of this study was to compare outcomes in patents with MA and TWA. Methods A prospective cohort study was conducted in the intensive cardiac care unit and enrolled 133 patients (59.6 ± 15.7 years; 65% men) admitted with acute heart failure (HF). Surface ECG and peripheral arterial blood pressure waveform via arterial line were recorded continuously. MA and TWA were measured by enhanced modified moving average method. All-cause death or heart transplant served as a combined primary endpoint. Results MA was observed in 28 patients (25%), whereas TWA was detected in 33 patients (33%). If present, MA was tightly coupled with TWA. Mitral flow deceleration time was shorter (127 ± 61 ms vs 172 ± 80 ms, P = .030), and left atrial systolic diameter was larger (5.1 ± 1.3 mm vs 4.4 ± 0.9 mm, P = .020) in patients with MA compared to those without. Mean TWA amplitude was larger in patients with both TWA and MA compared to patients with lone TWA (median 37 [interquartile range 26–61] µV vs 22 [21–23] µV, P = .045). After adjustment for New York Heart Association HF class, MA was associated with the primary endpoint (HR 2.3, 95% confidence interval 1.15–4.59, P = .018), whereas all lone TWA patients remained alive. Univariate Kaplan-Meier survival analysis showed the worst survival in patients with both MA and TWA at baseline, whereas patients without alternans had an intermediate probability of survival (Figure 1). All patients with lone TWA remained free from the primary endpoint. Conclusions HF patients with MA are characterized by restrictive diastolic dysfunction. The predictive value of TWA without simultaneous assessment of MA is inconclusive.