Dirk L. Brutsaert

Personality as independent predictor of long-term mortality in patients with coronary heart disease

BACKGROUND Emotional distress has been related to mortality in patients with coronary heart disease (CHD), but little is known about the role of personality in long-term prognosis. We postulated that type-D personality (the tendency to suppress emotional distress) was a predictor of long-term mortality in CHD, independently of established biomedical risk factors. METHODS We studied 268 men and 35 women with angiographically documented CHD, aged 31-79 years, who were taking part in an outpatient rehabilitation programme. All patients completed personality questionnaire at entry to the programme. We contacted them 6-10 years later (mean 7-9) to find out survival status. The main endpoint was death from all causes. FINDINGS At follow-up, 38 patients had died; there were 24 cardiac deaths. The rate of death was higher for type-D patients than for those without type-D (23 [27%]/85 vs 15 [7%]/218; p < 0.00001). The association between type-D personality and mortality was still evident more than 5 years after the coronary event and was found in both men and women. Mortality was also associated with impaired left ventricular function, three-vessel disease, low exercise tolerance, and the lack of thrombolytic therapy after myocardial infarction. When we controlled for these biomedical predictors in multiple logistic regression analysis, the impact of type-D remained significant (odds ratio 4.1 [95% CI 1.9-8.8]; p = 0.0004). In this group of CHD patients, type-D was an independent predictor of both cardiac and non-cardiac mortality. Social alienation and depression were also related to mortality, but did not add to the predictive power of type-D. INTERPRETATION We found that type-D personality was a significant predictor of long-term mortality in patients with established CHD, independently of biomedical risk factors. Personality traits should be taken into account in the association between emotional distress and mortality in CHD.

Diastolic failure: Pathophysiology and therapeutic implications

Primary diastolic dysfunction or failure is a distinct pathophysiologic entity. It results from increased resistance to ventricular filling, which leads to an inappropriate upward shift of the diastolic pressure-volume relation, particularly during exercise (exercise intolerance). The causes of diastolic failure are inappropriate tachycardia, decreased diastolic compliance and impaired systolic relaxation. Impaired (incomplete or slowed) systolic relaxation must be conceptually distinguished from compensatory prolonged systolic contraction (delayed or retarded relaxation). Optimal therapy will depend on the type of disease, the phase during the course of a given disease and the coexistence and relative contribution of various (de)compensatory processes. Treatment may consist of bradycardic, remodeling and lusitropic drugs.

Myocardial Contractile Response to Nitric Oxide and cGMP

BACKGROUND Cardiac endothelium releases a number of factors that may modulate performance of underlying cardiac muscle. Nitric oxide (NO), which accounts for the biological activity of the vascular endothelium-derived relaxing factor and relaxes vascular smooth muscle by elevating intracellular cGMP, may be involved in this cardiac modulation. METHODS AND RESULTS We examined the myocardial contractile effects of the NO-releasing nitrovasodilators sodium nitroprusside (SNP), 3-morpholino-sydnonimine (SIN-1), and S-nitroso-N-acetyl-penicillamine (SNAP); of a cGMP analogue, 8-bromo-cGMP; and of the cGMP-phosphodiesterase inhibitor zaprinast in isolated cat papillary muscle. Modulation of these effects by endocardial endothelium (EE) and by cholinergic and adrenergic stimulation was also investigated. Concentration-response curves with addition of NO-releasing nitrovasodilators (SNP, SIN-1, SNAP) and 8-bromo-cGMP resulted in a biphasic inotropic response. Although administration of low concentrations induced a positive inotropic effect, higher concentrations induced a negative inotropic effect. Both NO-induced positive and negative inotropic effects were attenuated by methylene blue, suggesting a role for cGMP. The response to high concentrations of 8-bromo-cGMP was shifted to the right in muscles with damaged EE, whereas cholinergic stimulation shifted the curve leftward. Zaprinast caused a monophasic concentration-dependent positive inotropic effect; damaging the EE shifted the terminal portion of the curve upward. Concomitant cholinergic or adrenergic stimulation modified the response to zaprinast into a negative inotropic response. CONCLUSIONS NO and cGMP induced a concentration-dependent biphasic contractile response. The myocardial contractile effects of NO and cGMP were modulated by the status of EE and by concomitant cholinergic or adrenergic stimulation.

Advanced chronic heart failure: A position statement from the Study Group on Advanced Heart Failure of the Heart Failure Association of the European Society of Cardiology.

Therapy has improved the survival of heart failure (HF) patients. However, many patients progress to advanced chronic HF (ACHF). We propose a practical clinical definition and describe the characteristics of this condition.

Cardiovascular side effects of cancer therapies: a position statement from the Heart Failure Association of the European Society of Cardiology

The reductions in mortality and morbidity being achieved among cancer patients with current therapies represent a major achievement. However, given their mechanisms of action, many anti‐cancer agents may have significant potential for cardiovascular side effects, including the induction of heart failure. The magnitude of this problem remains unclear and is not readily apparent from current clinical trials of emerging targeted agents, which generally under‐represent older patients and those with significant co‐morbidities. The risk of adverse events may also increase when novel agents, which frequently modulate survival pathways, are used in combination with each other or with other conventional cytotoxic chemotherapeutics. The extent to which survival and growth pathways in the tumour cell (which we seek to inhibit) coincide with those in cardiovascular cells (which we seek to preserve) is an open question but one that will become ever more important with the development of new cancer therapies that target intracellular signalling pathways. It remains unclear whether potential cardiovascular problems can be predicted from analyses of such basic signalling mechanisms and what pre‐clinical evaluation should be undertaken. The screening of patients, optimization of therapeutic schemes, monitoring of cardiovascular function during treatment, and the management of cardiovascular side effects are likely to become increasingly important in cancer patients. This paper summarizes the deliberations of a cross‐disciplinary workshop organized by the Heart Failure Association of the European Society of Cardiology (held in Brussels in May 2009), which brought together clinicians working in cardiology and oncology and those involved in basic, translational, and pharmaceutical science.

Personality and mortality after myocardial infarction.

Previous research showed a) emotional distress is a risk factor for mortality after myocardial infarction (MI) and b) emotional distress is linked to stable personality traits. In this study, we examined the role of these personality traits in mortality after MI. Subjects were 105 men, 45 to 60 years of age, who survived a recent MI. Baseline assessment included biomedical and psychosocial risk factors, as well as each patients personality type. After 2 to 5 (mean, 3.8) years of follow-up, 15 patients (14%) had died. Rate of death for patients with a distressed personality type (11/28 = 39%) was significantly greater than that for patients with other personality types (4/77 = 5%) (p <.0001). Patients with this personality type tend simultaneously to experience distress and inhibit expression of emotions. Low exercise tolerance, previous MI (p <.005), anterior MI, smoking, and age (p <.05) were also associated with mortality. A logistic regression model including these biomedical factors had a sensitivity for mortality of only 27%. The addition of distressed personality type in this model more than doubled its sensitivity. Of note, among patients with poor physical health, those with a distressed personality type had a five-fold mortality risk (p <.005). Consistent with the findings of other investigators, depression (p <.005), life stress, use of benzodiazepines (p <.01), and somatization (p <.05) were also related to post-MI mortality. These psychosocial risk factors were more prevalent in the distressed personality type than in the other personality types (p <.001-.05). Multiple logistic regression indicated that these psychosocial factors did not add to the predictive value of the distressed personality type. Hence, an important personality effect was observed despite the low power. This suggests that personality traits may play a role in the detrimental effect of emotional distress in MI patients.

Effects of damaging the endocardial surface on the mechanical performance of isolated cardiac muscle.

The mechanical properties of mammalian ventricular cardiac muscle have been studied in the presence and in the absence of an intact endocardial surface. Isotonic and isometric twitch contractions were obtained from papillary muscles of the right ventricle of cat at 29° and 37° C, at different extracellular calcium concentrations ([Ca2+]o), and at different initial muscle lengths. The endocardial surface was damaged by gentle abrasion of the muscle surface with a plastic blade or by brief immersion for 1 second with 1 % Triton X-100. Although there was no evidence of damage to myocardial cells, damaging the endocardial surface resulted in an immediate and irreversible abbreviation of the twitch contractions with, except at the highest [Ca2+]., a decrease in peak isometric twitch tension. These changes induced 1) an asymmetrical shift of the tension-[Ca2+] relation towards increasing [Ca2+] but with no effect at the highest [Ca2+]o, and 2) a rightward and downward shift of the length-tension relation. Both shifts were significantly more pronounced at 37° C than at 29° C; they were not accompanied by significant changes in Vmax. The asymmetrical shift of the tension-[Ca2+]o relation suggests that the endocardium-mediated chain of events may be mediated by changes in the sensitivity of the contractile proteins to Ca2+. This hypothesis is also supported by the similar pattern of changes (i.e., modulation of the onset of early tension decline) induced by decreasing length at each [Ca2+]. and by the removal of a functional endocardium. Accordingly, the endocardium may help to control the performance of the heart by modulating peak contractile performance and relaxation of the underlying myocardium.

Characteristics, outcomes, and predictors of mortality at 3 months and 1 year in patients hospitalized for acute heart failure

Acute heart failure (AHF) has a poor prognosis. We evaluated 3‐ and 12‐month mortality in different clinical classes of AHF patients from 30 European countries who were included in the EuroHeart Failure Survey (EHFS) II.

Analysis of relaxation in the evaluation of ventricular function of the heart

T HE MANAGEMENT of cardiac diseases has evolved from one of expectant observation to current medical and surgical interventions aimed at preserving or restoring myocardial function. This has led to a search for thorough understanding and evaluation of global and regional left ventricular function during systole and diastole. In the past, major research emphasis had been placed on the analysis of the contraction phase of systole. Only recently, our attention has been drawn also to the relaxation phase of systole and to diastole. In this respect, early detection of impaired relaxation has been emphasized for the evaluation of both global and regional ventricular function in patients with heart disease. Although early relaxation abnormalities have been found in various cardiac diseases that eventually lead to cardiac failure, such as hypertrophic and ischemic cardiomyopathy, the underlying mechanisms are as yet not fully understood.’ Given the recent progress in our understanding of the physiology and pathophysiology of the relaxation phase of systole of the heart as a muscle and pump,* these mechanisms can now be more easily appreciated. In this review, we will first summarize our present knowledge of relaxation of cardiac muscle. More specifically, we will describe how relaxation is controlled by three interacting determinants: (1) load, (2) (in)activation, and (3) nonuniform distribution of load and (in)activation in space and in time, and how this triple control constitutes a logical extension of a similar triple control of performance during contraction (Fig 1). Second, we will examine how this triple control applies to the intact in situ heart as a pump. Third, we will discuss how various factors, acting either alone or in concert, underlie relaxation abnormalities that occur early on in heart disease. Finally, we will critically review various measurements and indices of ventricular relaxation in view of these new concepts.

Nonuniformity: a physiologic modulator of contraction and relaxation of the normal heart.

Nonuniformity of mechanical performance is inherent to the multicellular nature and specific geometry and configuration of the ventricle of the heart. Although the concept of nonuniformity of the diseased heart is not new, ventricular function and the performance of the heart as a muscular pump cannot be understood unless nonuniform behavior is taken into account, even under normal conditions. Along with the loading conditions throughout the cardiac cycle and the time courses of activation and inactivation, the nonuniform behavior of load and of activation and inactivation in space and in time constitutes a third important determinant of mechanical performance and efficiency of the ventricle during both contraction and relaxation. Hence, a triad (load, activation-inactivation, nonuniformity) of controls regulates systolic function of the normal ventricle. In the diseased heart, even when loading and activation-inactivation are normal, the modulating role played by this nonuniformity can become imbalanced because of abnormal cavity size or shape or because of regional dysfunction. Such an imbalance would diminish external efficiency (the ratio of work performed to oxygen utilized) of the ventricle and result in incoordinate contraction and relaxation. These abnormalities, in turn, could exacerbate manifest cardiac failure.