Management of Hypertension in Patients With Ventricular Assist Devices: A Scientific Statement From the American Heart Association.

Mechanical circulatory support with durable continuous-flow ventricular assist devices has become an important therapeutic management strategy for patients with advanced heart failure. As more patients have received these devices and the duration of support per patient has increased, the postimplantation complications have become more apparent, and the need for approaches to manage these complications has become more compelling. Continuous-flow ventricular assist devices, including axial-flow and centrifugal-flow pumps, are the most commonly used mechanical circulatory support devices. Continuous-flow ventricular assist devices and the native heart have a constant physiological interplay dependent on pump speed that affects pressure-flow relationships and patient hemodynamics. A major postimplantation complication is cerebrovascular vascular accidents. The causes of cerebrovascular vascular accidents in ventricular assist device recipients may be related to hypertension, thromboembolic events, bleeding from anticoagulation, or some combination of these. The most readily identifiable and preventable cause is hypertension. Hypertension management in these patients has been hampered by the fact that it is difficult to accurately measure blood pressure because these ventricular assist devices have continuous flow and are often not pulsatile. Mean arterial pressures have to be identified by Doppler or oscillometric cuff and treated. Although guidelines for hypertension management after ventricular assist device implantation are based largely on expert consensus and conventional wisdom, the mainstay of treatment for hypertension includes guideline-directed medical therapy for heart failure with reduced ejection fraction because this may reduce adverse effects associated with hypertension and increase the likelihood of favorable ventricular remodeling. The use of systemic anticoagulation in ventricular assist device recipients may at a given blood pressure increase the risk of stroke.

Histamine H2 Receptor Antagonists, Left Ventricular Morphology, and Heart Failure Risk: The MESA Study.

BACKGROUND: Myocardial H2 receptor activation may promote cardiac fibrosis and apoptosis in pre-clinical models and histamine H2 receptor antagonist (H2RA) use may improve symptoms in participants with heart failure (HF); however, relationships between H2RA use, incident HF, and longitudinal change in left ventricular (LV) morphology are not known. OBJECTIVES: This study sought to determine whether H2RA use is associated with incident HF and change in LV morphology over time. METHODS: We included 6,378 men and women from MESA (Multi-Ethnic Study of Atherosclerosis), a multicenter prospective observational cohort of participants without cardiovascular disease at baseline. Cox proportional hazards were used to estimate the association between H2RA use and incident HF in adjusted models. In participants with cardiac magnetic resonance imaging, associations between H2RA use, baseline LV morphology (n = 4,691), and longitudinal change in the LV (n = 2,806) were estimated using linear regression. RESULTS: H2RAs were used by 313 participants but not by the other 6,065 individuals. During a median follow-up of 11.2 years, 236 participants developed HF. In adjusted models, baseline H2RA use relative to nonuse was associated with 62% lower risk for incident HF (p = 0.02). H2RA use was associated with preserved stroke volume, LV end-diastolic volume, and mass/volume ratio as measured by cardiac magnetic resonance imaging over approximately 10 years (all p < 0.05). There were no associations between H2RA use and LV mass or ejection fraction. CONCLUSIONS: H2RA use was associated with reduced risk for incident HF. Left heart morphology over time suggests less age-related change in H2RA users. These associations suggest histamine signaling may be important in the pathogenesis of HF. (Multi-Ethnic Study of Atherosclerosis [MESA]; NCT00005487).

Echocardiographic Ramp test for continuous-flow left ventricular assist devices: do loading conditions matter?

OBJECTIVES: This study investigated whether continuous AI and/or elevated mean arterial pressure (MAP) were associated with false positive results for flow obstruction in echocardiographic ramp speed tests in patients with a continuous-flow left ventricular assist device. BACKGROUND: Failure to reduce the left ventricular end-diastolic diameter (LVEDD) with increasing device speeds in a ramp test is predictive of pump obstruction. Aortic insufficiency (AI) or increased MAP can diminish the ability to unload the left ventricle. METHODS: LVEDD was plotted against device speed, and a linear function slope was calculated. A flat LVEDD slope (≥-0.16) was considered abnormal (suggestive of obstruction). Ramp test results were compared in patients with or without either AI or increased MAP at baseline speed, and receiver-operator characteristic (ROC) curves were constructed for predictors of device obstruction. Device thrombosis was confirmed by direct visualization of clot at explantation or on inspection by the manufacturer. RESULTS: Of 78 ramp tests (55 patients), 36 were abnormal (18 true positive, 18 false positive), and 42 were normal (37 true negative, 5 false negative). In patients with AI, LVEDD slope was -0.14 ± 0.17, which was consistent with device obstruction (vs. -0.25 ± 0.11 in patients without AI; p < 0.001), despite no difference in mean lactate dehydrogenase concentration between the 2 groups (1,301 ± 1,651 U/l vs. 1,354 ± 1,365 U/l; p = 0.91). Area under the ROC curve (AUC) for LVEDD slope was 0.76 and improved to 0.88 after removal of patients with AI from the study. LVEDD slope in patients with MAP ≥85 mm Hg was similar to that for device obstruction (-0.18 ± 0.07) and was abnormal in 6 of the 12 ramp tests performed. Combining LVEDD slope with lactate dehydrogenase concentration increased the AUC to 0.96 as an indicator of device obstruction. CONCLUSIONS: Abnormal loading conditions due to AI or elevated MAP may result in false positive ramp tests.

Cardiovascular MR imaging in cardio-oncology.

Patients with cancer are subject to short-term and long-term adverse cardiovascular outcomes from cancer therapies. It is important to identify patients at risk for cardiotoxicity so that appropriate therapy can be instituted early. Cardiovascular magnetic resonance (MR) imaging is emerging as a promising imaging modality with unique applications beyond standard left-ventricular systolic function assessment. It can provide comprehensive evaluation of most cardiac structures in one setting. This article provides an overview of cardiac MR imaging in cardio-oncology.

Apoptosis: a potentially reversible, meta-stable state of the heart.

Heart failure (HF) is a major problem worldwide, but its pathogenesis remains unclear. Apoptosis or programmed cell death is thought to play a crucial role in its progression. While primarily thought to be a method for cardiomyocyte loss, provocative newer data suggest that the apoptotic cell is not inevitably committed to death. Apoptosis might be one of the meta-stable transition states, like the hibernating myocardium, that may be reversible with appropriate therapy. The cell with activated apoptotic machinery is likely to contribute to reversible systolic dysfunction while awaiting its ultimate fate. We will briefly review some of the data to support such a concept. If proven correct, this may change our future preventive and therapeutic strategies. Methods to reverse apoptosis, thus might help restore systolic function and reverse remodeling or even prevent progression of heart failure.

The role of vitronectin receptor (alphavbeta3) and tissue factor in the pathogenesis of transplant coronary vasculopathy.

OBJECTIVES: This study was undertaken to test the hypothesis that transplant coronary vasculopathy (CV) is associated with increased myocardial protein expression of both tissue factor (TF) and integrin alphavbeta3. BACKGROUND: The vitronectin receptor (integrin alphavbeta3) and TF have recently been found to play a key role in apoptotic cell death and vascular endothelial cell injury. METHODS: A total of 77 heart transplant recipients underwent simultaneous endomyocardial biopsy and intravascular ultrasound (IVUS) at one year of transplant. Patients with pre-existing donor coronary atherosclerosis (n = 35) or with acute rejection (grade >1A, n = 10) at the time of the IVUS were excluded from the analysis. The remaining 32 patients constitute the cohort of the present study. A computerized biopsy score was derived based on the duration and severity of cellular rejection. Both TF and alphavbeta3 expression in the heart biopsy specimens were evaluated by immunoperoxidase histochemistry and Western blot analysis. RESULTS: Patients with CV (n = 24) had increased expression of alphavbeta3 (2.7-fold, p = 0.003) and TF (7.9-fold, p = 0.04) compared with patients without evidence of vasculopathy (n = 8). In the absence of myocardial fibrosis, alphavbeta3 expression correlated significantly with the cellular rejection score (r = 0.58, p = 0.02). CONCLUSIONS: Transplant vasculopathy is associated with increased expression of both TF and alphavbeta3. The significant correlation of alphavbeta3 with cellular rejection suggests an important role for this integrin in serving as a mechanistic link between cellular rejection and vasculopathy.

Infradesnivel del ST en la angina inestable: Caracterización clínica y pronóstica / ST depression in unstable angina: Clinical and prognostic characterization

La presencia de infradesnivel del segmento ST en el ECG de ingreso de pacientes internados con diagnóstico de angina inestable es marcador, según distintas series, de mala evolución hospitalaria. Con el objeto de caracterizar clínicamente a dicha población y detectar subgrupos de mayor riesgo dentro de la misma se analizaron los ECG de ingreso de 875 pacientes del Estudio ENAI. Los pacientes con infradesnivel del ST fueron más añosos y presentaron mayor prevalencia de hipertrofia ventricular izquierda que aquellos con ST nivelado. Su mortalidad hospitalaria fue mayor. La hipertrofia ventricular, la ausencia de taquicardia y la magnitud del infradesnivel señalaron subgrupos de peor evolución

Infradesnivel del ST en la angina inestable: Caracterización clínica y pronóstica / ST depression in unstable angina: Clinical and prognostic characterization

La presencia de infradesnivel del segmento ST en el ECG de ingreso de pacientes internados con diagnóstico de angina inestable es marcador, según distintas series, de mala evolución hospitalaria. Con el objeto de caracterizar clínicamente a dicha población y detectar subgrupos de mayor riesgo dentro de la misma se analizaron los ECG de ingreso de 875 pacientes del Estudio ENAI. Los pacientes con infradesnivel del ST fueron más añosos y presentaron mayor prevalencia de hipertrofia ventricular izquierda que aquellos con ST nivelado. Su mortalidad hospitalaria fue mayor. La hipertrofia ventricular, la ausencia de taquicardia y la magnitud del infradesnivel señalaron subgrupos de peor evolución (AU)