Mehdi Skhiri

Characteristics and Outcome After Hospitalization for Acute Right Heart Failure in Patients With Pulmonary Arterial Hypertension

Background— Although much is known about the risk factors for poor outcome in patients hospitalized with acute heart failure and left ventricular dysfunction, much less is known about the syndrome of acute heart failure primarily affecting the right ventricle (acute right heart failure). Methods and Results— By using Stanford Hospitals pulmonary hypertension database, we identified consecutive acute right heart failure hospitalizations in patients with PAH. We used longitudinal regression analysis with the generalized estimating equations method to identify factors associated with an increased likelihood of 90-day mortality or urgent transplantation. From June 1999 to September 2009, 119 patients with PAH were hospitalized for acute right heart failure (207 episodes). Death or urgent transplantation occurred in 34 patients by 90 days of admission. Multivariable analysis identified a higher respiratory rate on admission (>20 breaths per minute; OR, 3.4; 95% CI, 1.5–7.8), renal dysfunction on admission (glomerular filtration rate <45 mL/min per 1.73 m2; OR, 2.7; 95% CI, 1.2–6.3), hyponatremia (serum sodium ⩽136 mEq/L; OR, 3.6; 95% CI, 1.7–7.9), and tricuspid regurgitation severity (OR, 2.5 per grade; 95% CI, 1.2–5.5) as independent factors associated with an increased likelihood of death or urgent transplantation. Conclusions— These results highlight the high mortality after hospitalizations for acute right heart failure in patients with PAH. Factors identifiable within hours of hospitalization may help predict the likelihood of death or the need for urgent transplantation in patients with PAH.

Septal Curvature Is Marker of Hemodynamic, Anatomical, and Electromechanical Ventricular Interdependence in Patients with Pulmonary Arterial Hypertension

The objective of this study was to determine the factors independently associated with septal curvature in patients with pulmonary arterial hypertension (PAH).

Clinical and Functional Correlates of Early Microvascular Dysfunction After Heart Transplantation

Background—Microvascular dysfunction is emerging as a strong predictor of outcome in heart transplant recipients. At this time, the determinants and consequences of early microvascular dysfunction are not well established. The objective of the study was to determine the risk factors and functional correlates associated with early microvascular dysfunction in heart transplant recipients. Methods and Results—Sixty-three heart transplant recipients who had coronary physiology assessment, right heart catheterization, and echocardiography performed at the time of their first annual evaluation were included in the study. Microvascular dysfunction was assessed using the recently described index of microcirculatory resistance. The presence of microvascular dysfunction, predefined by an index of microcirculatory resistance >20, was observed in 46% of patients at 1 year. A history of acute rejection and undersized donor hearts were associated with microvascular dysfunction at 1 year, with odds ratio of 4.0 (1.3–12.8) and 3.6 (1.2–11.1), respectively. Patients with microvascular dysfunction had lower cardiac index (3.1±0.7 versus 3.5±0.7 L/min per m2; P=0.02) and mild graft dysfunction measured by echocardiography-derived left and right myocardial performance indices ([0.54±0.09 versus 0.43±0.09; P<0.01] and [0.47±0.14 versus 0.32±0.05; P<0.01], respectively). Microvascular dysfunction was also associated with a higher likelihood of death, graft failure, or allograft vasculopathy at 5 years after transplant (hazard ratio, 2.52 [95% CI, 1.04–5.91]). Conclusions—A history of acute rejection during the first year and smaller donor hearts were identified as risk factors for early microvascular dysfunction. Microvascular dysfunction assessed using index of microcirculatory resistances at 1 year was also associated with worse graft function and possibly worse clinical outcomes.

Incidence, Correlates, and Consequences of Acute Kidney Injury in Patients With Pulmonary Arterial Hypertension Hospitalized With Acute Right-Side Heart Failure

BACKGROUND Though much is known about the prognostic influence of acute kidney injury (AKI) in left-side heart failure, much less is known about AKI in patients with pulmonary arterial hypertension (PAH). METHODS AND RESULTS We identified consecutive patients with PAH who were hospitalized at Stanford Hospital for acute right-side heart failure. AKI was diagnosed according to the criteria of the Acute Kidney Injury Network. From June 1999 to June 2009, 105 patients with PAH were hospitalized for acute right-side heart failure (184 hospitalizations). AKI occurred in 43 hospitalizations (23%) in 34 patients (32%). The odds of developing AKI were higher among patients with chronic kidney disease (odds ratio [OR] 3.9, 95% confidence interval [CI] 1.8-8.5), high central venous pressure (OR 1.8, 95% CI 1.1-2.4, per 5 mm Hg), and tachycardia on admission (OR 4.3, 95% CI 2.1-8.8). AKI was strongly associated with 30-day mortality after acute right-side heart failure hospitalization (OR 5.3, 95% CI 2.2-13.2). CONCLUSIONS AKI is relatively common in patients with PAH and associated with a short-term risk of death.

Tratamiento basado en la evidencia de la insuficiencia cardiaca derecha: una revisión sistemática de un campo empírico

En los ultimos anos, varios estudios han indicado que la funcion ventricular derecha es un factor predictivo importante de la supervivencia en los pacientes con cardiopatias congenitas, hipertension pulmonar o insuficiencia cardiaca izquierda. Nuestro conocimiento de la insuficiencia cardiaca derecha ha mejorado considerablemente a lo largo de las ultimas dos decadas. En este articulo de revision, nuestro objetivo es presentar de forma critica la evidencia que subyace en el tratamiento de la insuficiencia cardiaca derecha. Se llevo a cabo una revision sistematica de la literatura medica, con el empleo de PubMed y el informe mas reciente del Registro Central Cochrane de Ensayos Controlados, para identificar estudios realizados entre enero de 1975 y enero de 2010. La busqueda se centro en ensayos observacionales y en ensayos controlados y aleatorizados, asi como en los metaanalisis. Se revisa sistematicamente la evidencia que subyace en el empleo de bloqueadores beta, inhibidores de la enzima de conversion de angiotensina, oxido nitrico inhalado, warfarina o terapia de resincronizacion en la insuficiencia cardiaca derecha. Se comentan tambien los nuevos tratamientos que estan surgiendo, como los moduladores metabolicos, asi como algunos aciertos y errores en el tratamiento de la insuficiencia cardiaca derecha.

Evidence-Based Management of Right Heart Failure: a Systematic Review of an Empiric Field

In recent years, several studies have shown that right ventricular function is an important predictor of survival in patients with congenital heart disease, pulmonary hypertension or left heart failure. Our understanding of right heart failure has improved considerably over the last two decades. In this review article, our objective was to provide a critical summary of the evidence underlying the management of right heart failure. A systematic review of the literature was performed using PubMed and the latest issue of the Cochrane Central Register of Controlled Trials to identify studies conducted between January 1975 and January 2010. The literature search encompassed observational studies, randomized controlled trials and meta-analyses. The evidence underlying the use of beta-blockade, angiotensin-converting enzyme inhibitors, inhaled nitric oxide, hydralazine, warfarin, and resynchronization therapy in right heart failure was systematically reviewed. Emerging new therapies, such as metabolic modulators, and the pearls and pitfalls of managing right heart failure are also discussed in the article.

Right Ventricular Dysfunction in Pulmonary Hypertension

We now know that there are many key differences between the right ventricle (RV) and the left ventricle (LV), ranging from embryological origin, structure, function (metabolism and perfusion), neurohormonal activation and response to increased afterload. Although the role of the RV in the low-pressure normal pulmonary circulation may not be critical, its critical role may become apparent in the diseased pulmonary circulation (e.g. pulmonary hypertension, PHT) or in high-altitude environments. Similarly, although in utero the RV is hypertrophied, within a few weeks after birth, its metabolism and structure is switching to the adult phenotype. Thus, the RV may be designed to be more “plastic.” However, its dynamic responses to physiologic or nonphysiologic triggers increase the risk of maladaptation. We now know that a maladaptive, failed RV is the most important factor in the morbidity and mortality in PHT, regardless of its specific cause. Right ventricular dysfunction is also a very strong predictor of outcome in patients with heart failure due to left ventricular dysfunction. Yet, at this time, few studies have focused on the RV, without extrapolating concepts form the LV. Thus, the concept of RV-specific therapies remains embryonic. In 2006, the NIH formed a task force focusing on increasing awareness and promoting RV studies specifically. Here we review the basic principles of right ventricular dysfunction, clinical diagnosis, as well as therapy, introducing the concept of RV-specific therapies. However, the biggest question in this field, i.e. what is the difference between the adapted RV (for example, the RV in a patient with severe PHT due to congenital heart disease that offers the patient decades-long survival) and the maladaptive RV [for example, the RV in a patient with idiopathic pulmonary arterial hypertension (PAH) of similar magnitude, which fails relatively quickly and allows only a few years of survival], remains unknown. It is hoped that the next edition of this textbook will provide some answers to this critical question.

Value of Circulating Cytokine Profiling During Submaximal Exercise Testing in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Myalgic Encephalomyelitis or Chronic Fatigue Syndrome (ME/CFS) is a heterogeneous syndrome in which patients often experience severe fatigue and malaise following exertion. Immune and cardiovascular dysfunction have been postulated to play a role in the pathophysiology. We therefore, examined whether cytokine profiling or cardiovascular testing following exercise would differentiate patients with ME/CFS. Twenty-four ME/CFS patients were matched to 24 sedentary controls and underwent cardiovascular and circulating immune profiling. Cardiovascular analysis included echocardiography, cardiopulmonary exercise and endothelial function testing. Cytokine and growth factor profiles were analyzed using a 51-plex Luminex bead kit at baseline and 18 hours following exercise. Cardiac structure and exercise capacity were similar between groups. Sparse partial least square discriminant analyses of cytokine profiles 18 hours post exercise offered the most reliable discrimination between ME/CFS and controls (κ = 0.62(0.34,0.84)). The most discriminatory cytokines post exercise were CD40L, platelet activator inhibitor, interleukin 1-β, interferon-α and CXCL1. In conclusion, cytokine profiling following exercise may help differentiate patients with ME/CFS from sedentary controls.