Psychological distress and personality factors in takotsubo cardiomyopathy.

BACKGROUND: Takotsubo cardiomyopathy (TCC) is a transient condition characterised by severe left ventricular dysfunction combined with symptoms and signs mimicking myocardial infarction. Emotional triggers are common, but little is known about the psychological background characteristics of TCC. This study examined whether patients with TTC have higher levels of psychological distress (depressive symptoms, perceived stress, general anxiety), illness-related anxiety and distinct personality factors compared with healthy controls and patients with heart failure. METHODS AND RESULTS: Patients with TCC (N = 18; mean age 68.3 ± 11.7 years, 77.8 % women) and two comparison groups (healthy controls: N = 19, age 60.0 ± 7.6, 68.4 % women and patients with chronic heart failure: N = 19, age 68.8 ± 10.1, 68.4 % women) completed standardised questionnaires to measure depression (PHQ­9), perceived stress (PSS-10), general anxiety (GAD-7), illness-related anxiety (WI-7) and personality factors (NEO-FFI and DS-14). Psychological measures were obtained at 23 ± 18 months following the acute TTC event. Results showed that patients with TCC had higher levels of depressive symptoms (5.2 ± 5.2 vs. 2.5 ± 2.4, p = 0.039) and illness-related anxiety (2.1 ± 1.7 vs. 0.7 ± 1.3, p = 0.005) compared with healthy controls. Patients with TCC did not display significantly elevated perceived stress (p = 0.072) or general anxiety (p = 0.170). Regarding personality factors, levels of openness were lower in TCC compared with healthy controls (34.2 ± 4.3 vs. 38.2 ± 5.6, p = 0.021). No differences between TCC and heart failure patients were found regarding the psychological measures. CONCLUSIONS: TCC is associated with higher levels of depressive symptoms, more illness-related anxiety and less openness compared with healthy controls. These data suggest that TCC is associated with adverse psychological factors that may persist well after the acute episode.

Central nervous system involvement in the autonomic responses to psychological distress.

Psychological distress can trigger acute coronary syndromes and sudden cardiac death in vulnerable patients. The primary pathophysiological mechanism that plays a role in stress-induced cardiac events involves the autonomic nervous system, particularly disproportional sympathetic activation and parasympathetic withdrawal. This article describes the relation between psychological distress and autonomic nervous system function, with a focus on subsequent adverse cardiovascular outcomes. The role of the central nervous system in these associations is addressed, and a systematic review is presented of studies examining the association between stress-induced central nervous system responses measured by neuroimaging techniques and autonomic nervous system activation. Results of the systematic review indicate that the primary brain areas involved in the autonomic component of the brain-heart association are the insula, medial prefrontal cortex, and cerebellum (based on 121 participants across three studies that fitted the inclusion criteria). Other areas involved in stress-induced autonomic modulation are the (anterior) cingulate cortex, parietal cortex, somatomotor cortex/precentral gyrus, and temporal cortex. The interaction between central and autonomic nervous system responses may have implications for further investigations of the brain-heart associations and mechanisms by which acute and chronic psychological distress increase the risk of myocardial infarction, cardiac arrhythmias, and sudden cardiac death.

Depression and anxiety as predictors of heart rate variability after myocardial infarction.

BACKGROUND: Reduced heart rate variability (HRV) is a prognostic factor for cardiac mortality. Both depression and anxiety have been associated with increased risk for mortality in cardiac patients. Low HRV may act as an intermediary in this association. The present study examined to what extent depression and anxiety differently predict 24-h HRV indices recorded post-myocardial infarction (MI). METHOD: Ninety-three patients were recruited during hospitalization for MI and assessed on self-reported symptoms of depression and anxiety. Two months post-MI, patients were assessed on clinical diagnoses of lifetime depressive and anxiety disorder. Adequate 24-h ambulatory electrocardiography data were obtained from 82 patients on average 78 days post-MI. RESULTS: In unadjusted analyses, lifetime diagnoses of major depressive disorder was predictive of lower SDNN [standard deviation of all normal-to-normal (NN) intervals; beta=-0.26, p=0.022] and SDANN (standard deviation of all 5-min mean NN intervals; beta=0.25, p=0.023), and lifetime anxiety disorder of lower RMSSD (root mean square of successive differences; beta=-0.23, p=0.039). Depression and anxiety symptoms did not significantly predict HRV. After adjustment for age, sex, cardiac history and multi-vessel disease, lifetime depressive disorder was no longer predictive of HRV. Lifetime anxiety disorder predicted reduced high-frequency spectral power (beta=-0.22, p=0.039) and RMSSD (beta=-0.25, p=0.019), even after additional adjustment of anxiety symptoms. CONCLUSIONS: Clinical anxiety, but not depression, negatively influenced parasympathetic modulation of heart rate in post-MI patients. These findings elucidate the physiological mechanisms underlying anxiety as a risk factor for adverse outcomes, but also raise questions about the potential role of HRV as an intermediary between depression and post-MI prognosis.

Autonomic dysfunction in patients with mild heart failure and coronary artery disease and the effects of add-on beta-blockade.

AIM: Autonomic impairment is related to the incidence of sudden death in chronic heart failure (CHF). Our objective was to study autonomic profiles in patients with mild CHF due to coronary artery disease, and to investigate the value of add-on beta-blockade. METHODS AND RESULTS: Measures of autonomic function (plasma norepinephrine, heart rate [HR] variability, autonomic function testing), and exercise capacity, were compared between 24 patients with mild CHF, and 24 healthy controls. In this mechanistic study, we assessed the effect of 26 weeks metoprolol treatment in a double-blind, randomized, placebo-controlled design. All patients received metoprolol sustained release (200 mg; n=12) or placebo (n=12). Assessments were made at baseline and after 10 and 26 weeks' treatment. At baseline, norepinephrine levels were elevated, while HR variability parameters were decreased in patients vs. controls (both P<0.05). Autonomic function testing showed only small differences, although significant alterations were observed with deep breathing and head up tilting (both P<0.05). After 26 weeks', metoprolol did not affect exercise capacity or norepinephrine concentrations. In contrast, HR variability was markedly improved in metoprolol-treated patients vs. placebo-treated patients (P<0.05). In particular, a shift toward normal in the sympathovagal balance was observed (P<0.05). Autonomic function testing showed only small, and generally non-significant trends after metoprolol. CONCLUSIONS: Marked autonomic abnormalities are already present in mild CHF, which may be (partially) reversed by metoprolol. These observations support the reported reduction of sudden death by beta-blockade in patients with CHF.

Comparison between iodine 123 metaiodobenzylguanidine scintigraphy and heart rate variability for the assessment of cardiac sympathetic activity in mild to moderate heart failure.

This study demonstrates that in patients with mild to moderate heart failure, cardiac metaiodobenzylguanidine (MIBG) washout positively correlates with normalized low-frequency power in the heart rate variability spectrum. Alterations of the cardiac sympathetic nervous system could be detected with MIBG scintigraphy in patients with normal plasma norepinephrine levels. Therefore cardiac MIBG washout may be a valuable noninvasive technique to assess early alterations in cardiac sympathetic activity that may have potential clinical implications in patients with mild to moderate heart failure.

Alterations in the prognosis of chronic heart failure: an overview of the major mortality trials.

Treatment of chronic heart failure (CHF) remains a major medical problem. Although in the last decades the benefits of several therapies in different patient populations with left ventricular dysfunction have been established, morbidity and mortality of CHF patients are high. Consequently, in the last decade improvement of survival has become the primary therapeutic endpoint in CHF studies, and the evaluation of the influence of (new) drugs on mortality has become crucial. In the present article an overview of the large mortality trials is given, and the shifts and alterations in the drug treatment strategy of CHF are discussed.

Hemodynamic and autonomic effects of intravenous saterinone in patients with chronic heart failure.

In this study, the hemodynamic and neurohumoral/autonomic effects of intravenous saterinone (a selective phosphodiesterase type III inhibitor, with additional alpha 1-blocking properties) were evaluated. In a double-blind, placebo-controlled design, 36 patients with moderate to severe heart failure were studied (saterinone, n = 24; placebo, n = 12). Invasive hemodynamic measurements, by using right-heart catheterization, were performed, as well as measurement of plasma neurohormones and analysis of heart rate variability (HRV), to study drug influences on neurohumoral activation and autonomic tone. Systemic vascular resistance significantly decreased during saterinone infusion, accompanied by a decrease in systemic blood pressure (both p values < 0.05) and an increase in heart rate (p = 0.05). Filling pressures also decreased during saterinone, but this was statistically significant only for pulmonary capillary wedge pressure, whereas the cardiac index remained unaffected. Plasma neurohormones (norepinephrine, epinephrine, and renin activity) were not significantly influenced by saterinone. HRV analysis revealed no significant effect of saterinone on autonomic tone. These results suggest that intravenous saterinone has a significant vasodilating effect in patients with moderate to severe chronic heart failure (CHF), without exerting an adverse effect on the autonomic nervous system, as demonstrated by assessment of plasma neurohormones and HRV analysis.

Prognostic value of heart rate variability in chronic congestive heart failure secondary to idiopathic or ischemic dilated cardiomyopathy.

To study the prognostic value of heart rate (HR) variability in heart failure, risk assessment of clinical and HR variability parameters was performed in 159 patients with stable chronic heart failure. Besides low left ventricular ejection fraction, HR variability parameters reflecting impaired vagal tone (SDNN, pNN50) were found to predict an increased risk of cardiac death and death due to progressive pump failure.

Clinical and autonomic effects of ibopamine as adjunct to angiotensin-converting enzyme inhibitors in chronic heart failure.

BACKGROUND: The purpose of this study was to determine the additive value of ibopamine in heart failure patients who are treated with angiotensin-converting enzyme inhibitors. Ibopamine exerts hemodynamic and neurohumoral effects, and is beneficial in mild heart failure; however, its additive value in more advanced disease in unclear. METHODS AND RESULTS: The study was a stand-alone, double-blind, randomized parallel group comparison of ibopamine (100 mg 3 times daily) and placebo in 59 patients with New York Heart Association functional class III-IV heart failure. Patients were clinically stable on drug treatment, including an angiotensin-converting enzyme inhibitor, and they were randomized to ibopamine (n = 29) or placebo (n = 30). Assessments were performed at baseline and after 3 months of treatment, and included measurement of peak oxygen consumption, plasma neurohormones, ambulatory arrhythmias, and heart rate variability. At baseline, the two groups were well matched, including age (mean, 63 years), left ventricular ejection fraction (0.23), and peak oxygen consumption (15.4 mL/min/kg). After 3 months, four patients had dropped out of the study because of progressive heart failure (ibopamine, n = 1; placebo, n = 3; not significant) and two because of side effects (n = 1/1). Exercise time and peak oxygen consumption were not significantly affected (exercise time: ibopamine, +54 [95% confidence interval, -12, 120] seconds; placebo, +19 [-42, 81] seconds; peak oxygen consumption: ibopamine, +0.3 [-0.5, 1,2] mL/min/kg; placebo, +0.2 [-0.7, 1.0] mL/min/kg). Plasma neurohormones and ventricular arrhythmias during ambulatory monitoring were also unaffected. In contrast, heart rate variability parameters, in particular those associated with vagal tone (rMMSD, high-frequency power), significantly increased after 3 months on ibopamine (P = .01 vs placebo). CONCLUSIONS: In this group of patients with clinically stable moderate to severe chronic heart failure, only a marginal and statistically nonsignificant effect on clinical parameters was observed after 3 months of treatment with ibopamine. Heart rate variability parameters, however, were significantly affected by ibopamine, despite the absence of an effect on plasma neurohormones.

Relation between severity of disease and impairment of heart rate variability parameters in patients with chronic congestive heart failure secondary to coronary artery disease.

The present data show that HR variability has a statistically significant, but moderate, correlation with clinical variables of severity of CHF. Therefore, HR variability analysis may be a new, important tool in the clinical assessment of CHF patients.

Predictors of mortality in patients with sustained ventricular tachycardias or ventricular fibrillation and depressed left ventricular function: importance of beta-blockade.

To study prognostic factors in patients with sustained ventricular tachycardias (VT) or ventricular fibrillation (VF) complicated by left ventricular dysfunction, we evaluated the predictive value of demographic, clinical, and hemodynamic parameters for cardiac mortality and sudden cardiac death in 85 patients with VT or VF and left ventricular ejection fraction < 0.45 (mean 0.27 +/- 0.10). Patients underwent serial drug testing and received appropriate antiarrhythmic treatment, with amiodarone given as last-resort therapy. During a follow-up of 24 +/- 13 months, 23 patients died of cardiac causes, and 18 of them died suddenly. Left ventricular ejection fraction < or = 0.27 and amiodarone treatment were related to greater cardiac mortality and increased risk of sudden cardiac death, whereas beta-blockade was associated with improved survival. In the multivariate model cardiac mortality was best predicted by a left ventricular ejection fraction < or = 0.27, and absence of beta-blockade and severe left ventricular dysfunction were the strongest predictors of sudden cardiac death. We conclude that severe left ventricular dysfunction predicts increased cardiac mortality and high risk of sudden cardiac death. Moreover, beta-blocking treatment is associated with lower cardiac mortality and a reduced risk of sudden cardiac death in patients with sustained VT or VF and depressed left ventricular function. beta-Blocking agents may therefore be an important addition to conventional antiarrhythmic treatment in patients with VT or VF and left ventricular dysfunction.

Effect of exercise on cycle length in atrial flutter.

OBJECTIVE: To examine the effect of exercise on cycle length in atrial flutter. PATIENTS: 15 patients with chronic atrial flutter. Seven patients were taking digoxin and six verapamil; two were not taking medication. METHODS: All patients underwent bicycle ergometry. Flutter cycle length was measured at rest and at peak exercise. RESULTS: Mean flutter cycle length increased from 245 ms to 256 ms (P = 0.002). Six patients developed 1:1 atrioventricular conduction. Significant increases in flutter cycle length were observed irrespective of development of 1:1 atrioventricular conduction and use of digoxin and verapamil. CONCLUSION: Exercise prolongs flutter cycle length. This effect would promote development of 1:1 atrioventricular conduction during exercise, causing inordinately high ventricular rates.

Value of ambulatory electrocardiographic monitoring to identify increased risk of sudden death in patients with left ventricular dysfunction and heart failure.

To examine the predictive value of ventricular arrhythmias on ambulatory electrocardiographic (ECG) monitoring, 211 patients with left ventricular dysfunction and congestive heart failure (76% men, age 63 +/- 4 years, left ventricular ejection fraction 0.26 +/- 0.10) were studied. During a follow-up of 21 +/- 11 months, there were 45 cardiac deaths: 22 were due to progressive pump failure and 23 were sudden. Patients with a low left ventricular ejection fraction (< or = 0.27) and ventricular tachycardia on 24 h ECG were at higher risk of dying suddenly and from progressive pump failure (both P < 0.0001). Patients who died suddenly were found to have significantly longer (P = 0.003) and faster (P = 0.029) ventricular tachycardias on their baseline ambulatory ECG, than survivors. This association was not observed in patients who died of progressive pump failure. Therefore, low left ventricular ejection fraction and ventricular tachycardia on 24 h ECG recording predict an increased risk of cardiac mortality. Our results also suggest that longer and faster ventricular tachycardia recorded by 24 h ECG may identify patients at risk of sudden death, a finding which has not been described before.