Is abnormal myocardial repolarization associated with the occurrence of malignant tachyarrhythmias in Takotsubo cardiomyopathy?

Background: Abnormalities of cardiac repolarization are a hallmark of Takotsubo cardiomyopathy (TC), but their association with the occurrence of syncope and ventricular tachyarrhythmias is unknown. This study sought to assess the relationship between myocardial repolarization and malignant tachyarrhythmias in TC.Methods: Clinical data and electrocardiographic repolarization parameters of 28 patients with TC and ventricular tachyarrhythmias (n = 26) or syncope (n = 2) were compared to data from 20 randomly selected patients with TC but without ventricular tachyarrhythmias or syncope.Results: Study patients had signifi cantly lower ejection fraction (EF) compared with controls (35 ± 14% vs. 46 ± 10%, p = 0.006). On day 1, no signifi cant differences in repolarization parameters were observed. However, in the subgroup with ventricular fi brillation ([VF]; n = 10), Tpeak-Tend in lead V6 was significantly prolonged (97 ± 20 vs. 85 ± 19 ms; p = 0.04). Similarly, in the subgroup with torsade de pointes ([TdP]; n = 5) Tpeak-Tend in lead V4 wasprolonged (127 ± 21 vs. 94 ± 27 ms; p = 0.001). On day 3, Tpeak-Tend in lead V3 (130 ± 51 vs. 105 ± 21 ms, p = 0.049) and Tpeak-Tend dispersion (56 ± 33 vs. 36 ± 21 ms; p = 0.03) were signifi cantly longer in study patients. The difference in Tpeak-Tend in lead V3 was borderline in the VF subgroup, but significant in the subgroup with TdP. The latter grouphad also longer Tpeak-Tend in lead V4 and longer corrected QT interval in leads V3 and V4.Conclusions: Patients with TC who experience malignant tachyarrhythmias have lower EF and a more pronounced alteration of the spatial dispersion of ventricular repolarization

Spiritual Well-Being and Depression in Patients with Heart Failure

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 < .0001), while faith was only modestly associated (r = −.38, P < .01). In a regression analysis accounting for gender, income, and other risk factors for depression (social support, physical symptoms, and health status), greater spiritual well-being continued to be significantly associated with less depression (P = .05). Between the 2 spiritual well-being subscales, only meaning/peace contributed significantly to this effect (P = .02) and accounted for 7% of the variance in depression. CONCLUSIONS: Among outpatients with heart failure, greater spiritual well-being, particularly meaning/peace, was strongly associated with less depression. Enhancement of patients’ sense of spiritual well-being might reduce or prevent depression and thus improve quality of life and other outcomes in this population

Psychiatric symptoms, personality profile and Takotsubo syndrome: clinical considerations

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

Abstract 1753: Transcriptomic based Biomarkers Contain Diagnostic and Prognostic Information about Patients with new onset Heart Failure

INTRODUCTION: One of the clinical dilemmas in cardiology is to accurately diagnose the etiology of patients with new onset heart failure such as to differentiate between potentially reversible myocarditis from idiopathic dilated cardiomyopathy (IDCM). Furthermore, it is difficult to predict the clinical trajectory of patients with IDCM. We hypothesized that the transcriptomic signatures generated from endomyocardial biopsies, obtained from patients at first presentation of heart failure, could serve as novel biomarkers to distinguish between myocarditis and IDCM as well as to predict the prognosis of patients classified as having IDCM. METHODS AND RESULTS: Endomyocardial biopsy samples were collected from 68 patients with new onset heart failure due to IDCM (n=49) and myocarditis (n=19). The average follow-up was 5 years and included information on mortality, need for left ventricular assist device (LVAD), or heart transplant. We used the U133 Plus 2.0 microarray (Affymetrix) and data analysis was performed with Significance Analysis of Microarrays (SAM) and Prediction Analysis of Microarrays (PAM). First, we identified a molecular signature of 39 genes in our training cohort (n=25 IDCM and n=8 myocarditis). When tested in independent patients (myocarditis: n=11; IDCM: n=11), this signature performed with 97% accuracy. Next, we identified a transcriptomic signature of 45 genes in a group of patients with IDCM that delineated between patients classified as having a good prognosis (event free survival > 5 years; n=18) vs a bad prognosis (death or requirement for insertion of LVAD or tx within 2 years of presentation; n=12). We tested this biomarker in independent samples and were able to predict prognosis with 87% accuracy. The transcriptomic biomarker was substantially more accurate in assigning prognosis than the Seattle Heart Failure Score (p=0.011). CONCLUSION: Together these findings illustrate the potential utility of using transcriptomic biomarkers generated from a single endomyocardial biopsy to improve the accuracy of diagnosis and prognosis in patients with new onset heart failure. This creates novel modalities to enhance management and identification of patients at highest risk for complications of heart failure in the short term

Cardiac nitric oxide production due to angiotensin-converting enzyme inhibition decreases beta-adrenergic myocardial contractility in patients with dilated cardiomyopathy

AbstractOBJECTIVESThis study tested the hypothesis that angiotensin-converting enzyme (ACE) inhibitors attenuate beta-adrenergic contractility in patients with idiopathic dilated cardiomyopathy (DCM) through nitric oxide (NO) myocardial signaling.BACKGROUNDThe ACE inhibitors increase bradykinin, an agonist of NO synthase (NOS). Nitric oxide inhibits beta-adrenergic myocardial contractility in patients with heart failure.METHODSThe study patients were given the angiotensin-1 (AT-1) receptor antagonist losartan for one week. The hemodynamic responses to intravenous dobutamine were determined before and during intracoronary infusion of enalaprilat (0.2 mg/min) with and without the NOS inhibitor NG-monomethyl-L-arginine (L-NMMA, 5 mg/min).RESULTSIn patients with DCM (n = 8), dobutamine increased the peak rate of rise of left ventricular pressure (+dP/dt) by 49 ± 8% (p < 0.001) and ventricular elastance (Ees) by 53 ± 16% (p < 0.03). Co-infusion with enalaprilat decreased +dP/dt to 26 ± 12% and Eesto −2 ± 17% above baseline (p < 0.05), and this anti-adrenergic effect was reversed by L-NMMA co-infusion (p < 0.05 vs. enalaprilat). In addition, intracoronary enalaprilat reduced left ventricular end-diastolic pressure (LVEDP), but not left ventricular end-diastolic volume, consistent with increased left ventricular distensibility. Infusion with L-NMMA before enalaprilat in patients with DCM (n = 5) prevented the reduction in +dP/dt, Eesand LVEDP. In patients with normal left ventricular function (n = 5), enalaprilat did not inhibit contractility or reduce LVEDP during dobutamine infusion.CONCLUSIONSEnalaprilat attenuates beta-adrenergic contractility and enhances left ventricular distensibility in patients with DCM, but not in subjects with normal left ventricular function. This response is NO modulated and occurs in the presence of angiotensin receptor blockade. These findings may have important clinical and pharmacologic implications for the use of ACE inhibitors, AT-1 receptor antagonists and their combination in the treatment of heart failure

Psychiatric history, post-discharge distress, and personality characteristics among incident female cases of takotsubo cardiomyopathy: A case-control study

BACKGROUND: The role of psychological factors in the onset of takotsubo cardiomyopathy (TC) is still controversial. Associations with previous psychiatric conditions are registry-based; associations with personality characteristics and psychological sequelae of TC have been largely unexplored. This case-control study sought to study pre-admission psychiatric morbidity, personality traits, and post-discharge distress in incident cases of TC. METHODS: TC cases (Mayo clinic criteria) and acute myocardial infarction (MI) controls were recruited among women admitted to two Emergency Departments in New England. Healthy controls (HC) were recruited from a volunteers\u27 registry. Preadmission psychiatric history (DSM-IV-TR) was abstracted from the medical record. PTSD symptoms (Impact of Events Scale); distress (Hospital Anxiety and Depression Scale); perceived stress (PS scale) and personality traits (optimism; hostility, type D personality) were collected via phone interview one month after discharge. RESULTS: From March 2013 through October 2015, 107 participants (45 TC, 32 MI and 30 HC) were enrolled. The prevalence of preadmission anxiety disorders was 24.4% in TC, 9.4% in MI, and 0 in HC (p = 0.007) while that of mood disorders was similar across groups. TC had higher psychological distress, perceived stress, and PTSD symptoms post-discharge vs. MI and HC. In adjusted models, PTSD symptoms remained higher in TC vs. MI (b = 0.55, p \u3c 0.05) and vs. HC (b = 0.92, p \u3c 0.01). Optimism and hostility scores were similar across groups, while type D (social inhibition) scores were higher in TC and MI vs. HC. CONCLUSIONS: Preadmission anxiety, but not depression, was associated with the occurrence of TC. High distress and PTSD symptoms post-discharge indicate that TC women may be at risk for poor psychological adjustment

Transcriptomic Analysis Identifies the Effect of Beta-Blocking Agents on a Molecular Pathway of Contraction in the Heart and Predicts Response to Therapy

Over the last decades, beta-blockers have been a key component of heart failure therapy. However, currently there is no method to identify patients who will benefit from beta-blocking therapy versus those who will be unresponsive or worsen. Furthermore, there is an unmet need to better understand molecular mechanisms through which heart failure therapies, such as beta-blockers, improve cardiac function, in order to design novel targeted therapies. Solving these issues is an important step towards personalized medicine. Here, we present a comprehensive transcriptomic analysis of molecular pathways that are affected by beta-blocking agents and a transcriptomic biomarker to predict therapy response. • Endomyocardial biopsy obtained from patients with new onset heart failure. • Patients are followed long-term to determine clinical outcome and prognosis. • Total RNA is purified from the endomyocardial biopsy specimen and subjected to microarray analysis. • Pathway discovery and development of transcriptomic biomarkers are determined that predict clinical response to beta-adrenergic antagonists