Impact of salt on cardiac differential gene expression and coronary lesion in normotensive mineralocorticoid-treated mice.

We previously reported that excess of deoxycorticosterone-acetate (DOCA)/salt-induced cardiac hypertrophy in the absence of hypertension in one-renin gene mice. This model allows us to study molecular mechanisms of high-salt intake in the development of cardiovascular remodeling, independently of blood pressure in a high mineralocorticoid state. In this study, we compared the effect of 5-wk low- and high-salt intake on cardiovascular remodeling and cardiac differential gene expression in mice receiving the same amount of DOCA. Differential gene and protein expression was measured by high-density cDNA microarray assays, real-time PCR and Western blot analysis in DOCA-high salt (HS) vs. DOCA-low salt (LS) mice. DOCA-HS mice developed cardiac hypertrophy, coronary perivascular fibrosis, and left ventricular dysfunction. Differential gene and protein expression demonstrated that high-salt intake upregulated a subset of genes encoding for proteins involved in inflammation and extracellular matrix remodeling (e.g., Col3a1, Col1a2, Hmox1, and Lcn2). A major subset of downregulated genes encoded for transcription factors, including myeloid differentiation primary response (MyD) genes. Our data provide some evidence that vascular remodeling, fibrosis, and inflammation are important consequences of a high-salt intake in DOCA mice. Our study suggests that among the different pathogenic factors of cardiac and vascular remodeling, such as hypertension and mineralocorticoid excess and sodium intake, the latter is critical for the development of the profibrotic and proinflammatory phenotype observed in the heart of normotensive DOCA-treated mice.

Cardiac function assessed by transesophageal echocardiography during pectus excavatum repair.

BACKGROUND: We assessed end-diastolic right ventricular (RV) dimensions and left ventricular (LV) ejection fraction by use of intraoperative transesophageal echocardiography before and after surgical correction of pectus excavatum in adults. METHODS: A prospective study was conducted including 17 patients undergoing surgical correction of pectus excavatum according to the technique of Ravitch-Shamberger between 1999 and 2004. Intraoperative transesophageal echocardiography was performed under general anesthesia before and after surgery to assess end-diastolic RV dimensions and LV ejection fraction. The end-diastolic RV diameter and area were measured in four-chamber and RV inflow-outflow view, and the RV volume was calculated from these data. The LV was assessed by transgastric short-axis view, and its ejection fraction was calculated by use of the Teichholz formula. RESULTS: The end-diastolic RV diameter, area, and volume all significantly increased after surgery (mean values +/- SD, respectively: 2.4 +/- 0.8 cm versus 3.0 +/- 0.9 cm, p < 0.001; 12.5 +/- 5.2 cm(2) versus 18.4 +/- 7.5 cm(2), p < 0.001; and 21.7 +/- 11.7 mL versus 40.8 +/- 23 mL, p < 0.001). The LV ejection fraction also significantly increased after surgery (58.4% +/- 15% versus 66.2% +/- 6%, p < 0.001). CONCLUSIONS: Surgical correction of pectus excavatum according to Ravitch-Shamberger technique results in a significant increase in end-diastolic RV dimensions and a significantly increased LV ejection fraction.

Cardiomyopathie de tako-tsubo: une entité clinique rare et méconnue [Tako-tsubo cardiomyopathy: a rare and badly known clinical entity]

Tako-tsubo cardiomyopathy or "transient left ventricular (LV) apical ballooning" clinically presents like acute myocardial infarction without angiographic stenosis on coronary angiogram and a transient (reversible) LV apical ballooning. We discuss here about a 56-year-old woman complains of first constrictive chest pain with ST elevation in leads V2-V6 and minimal enzymatic release. Coronary angiogram demonstrates vessels without stenosis and the left ventriculogram an extensive LV apical wall motion abnormalities. LV dysfunction will only be transient since 24 hours after admission echographic images demonstrate quite complete recovery of LV systolic function. The pain disappears 12 hours after admission and the creatine kinase level normalize after 48 hours.

RV contractility and exercise-induced pulmonary hypertension in chronic mountain sickness: a stress echocardiographic and tissue Doppler imaging study.

OBJECTIVES: The aim of this study was to evaluate right ventricular (RV) and left ventricular function and pulmonary circulation in chronic mountain sickness (CMS) patients with rest and stress echocardiography compared with healthy high-altitude (HA) dwellers. BACKGROUND: CMS or Monge's disease is defined by excessive erythrocytosis (hemoglobin >21 g/dl in males, 19 g/dl in females) and severe hypoxemia. In some cases, a moderate or severe increase in pulmonary pressure is present, suggesting a similar pathogenesis of pulmonary hypertension. METHODS: In La Paz (Bolivia, 3,600 m sea level), 46 CMS patients and 40 HA dwellers of similar age were evaluated at rest and during semisupine bicycle exercise. Pulmonary artery pressure (PAP), pulmonary vascular resistance, and cardiac function were estimated by Doppler echocardiography. RESULTS: Compared with HA dwellers, CMS patients showed RV dilation at rest (RV mid diameter: 36 ± 5 mm vs. 32 ± 4 mm, CMS vs. HA, p = 0.001) and reduced RV fractional area change both at rest (35 ± 9% vs. 43 ± 9%, p = 0.002) and during exercise (36 ± 9% vs. 43 ± 8%, CMS vs. HA, p = 0.005). The RV systolic longitudinal function (RV-S') decreased in CMS patients, whereas it increased in the control patients (p < 0.0001) at peak stress. The RV end-systolic pressure-area relationship, a load independent surrogate of RV contractility, was similar in CMS patients and HA dwellers with a significant increase in systolic PAP and pulmonary vascular resistance in CMS patients (systolic PAP: 50 ± 12 mm Hg vs. 38 ± 8 mm Hg, CMS vs. HA, p < 0.0001; pulmonary vascular resistance: 2.9 ± 1 mm Hg/min/l vs. 2.2 ± 1 mm Hg/min/l, p = 0.03). Both groups showed comparable systolic and diastolic left ventricular function both at rest and during stress. CONCLUSIONS: Comparable RV contractile reserve in CMS and HA suggests that the lower resting values of RV function in CMS may represent a physiological adaptation to chronic hypoxic conditions rather than impaired RV function. (Chronic Mountain Sickness, Systemic Vascular Function [CMS]; NCT01182792).

Suivi cardiologique d'un patient oncologique [Cardiologic follow up of an oncologic patient]

Recent progress in cancer therapy has dramatically modified the course and prognosis of some malignancies. Chemo and radiotherapy, along with newer targeted treatments, are given to control symptoms, postpone relapse, or attempt cure. However, many of these regimens are associated with adverse cardiovascular effects such as impaired left ventricular function, myocardial ischemia, hypertension, and arrhythmia. Awareness of potential cardiotoxicity is important, as it may allow practitioners to recognize early signs of cardiac complications and to adapt therapy in order to limit detrimental effects. Diagnosis of cardiovascular complications may iustify the introduction of cardiologic therapies, and may require the reassessment of risk/benefit ratios related to specific cancer therapy. Screening and follow up strategies are proposed.

Inflammatory markers and incident heart failure risk in older adults: the Health ABC (Health, Aging, and Body Composition) study.

OBJECTIVES: The purpose of this study was to evaluate the association between inflammation and heart failure (HF) risk in older adults. BACKGROUND: Inflammation is associated with HF risk factors and also directly affects myocardial function. METHODS: The association of baseline serum concentrations of interleukin (IL)-6, tumor necrosis factor-alpha, and C-reactive protein (CRP) with incident HF was assessed with Cox models among 2,610 older persons without prevalent HF enrolled in the Health ABC (Health, Aging, and Body Composition) study (age 73.6 +/- 2.9 years; 48.3% men; 59.6% white). RESULTS: During follow-up (median 9.4 years), HF developed in 311 (11.9%) participants. In models controlling for clinical characteristics, ankle-arm index, and incident coronary heart disease, doubling of IL-6, tumor necrosis factor-alpha, and CRP concentrations was associated with 29% (95% confidence interval: 13% to 47%; p < 0.001), 46% (95% confidence interval: 17% to 84%; p = 0.001), and 9% (95% confidence interval: -1% to 24%; p = 0.087) increase in HF risk, respectively. In models including all 3 markers, IL-6, and tumor necrosis factor-alpha, but not CRP, remained significant. These associations were similar across sex and race and persisted in models accounting for death as a competing event. Post-HF ejection fraction was available in 239 (76.8%) cases; inflammatory markers had stronger association with HF with preserved ejection fraction. Repeat IL-6 and CRP determinations at 1-year follow-up did not provide incremental information. Addition of IL-6 to the clinical Health ABC HF model improved model discrimination (C index from 0.717 to 0.734; p = 0.001) and fit (decreased Bayes information criterion by 17.8; p < 0.001). CONCLUSIONS: Inflammatory markers are associated with HF risk among older adults and may improve HF risk stratification.

Interactions between respiration and systemic hemodynamics. Part II: practical implications in critical care.

In Part I of this review, we have covered basic concepts regarding cardiorespiratory interactions. Here, we put this theoretical framework to practical use. We describe mechanisms underlying Kussmaul's sign and pulsus paradoxus. We review the literature on the use of respiratory variations of blood pressure to evaluate volume status. We show the possibilities of attaining the latter aim by investigating with ultrasonography how the geometry of great veins fluctuates with respiration. We provide a Guytonian analysis of the effects of PEEP on cardiac output. We terminate with some remarks on the potential of positive pressure breathing to induce acute cor pulmonale, and on the cardiovascular mechanisms that at times may underly the failure to wean a patient from the ventilator.

Transcatheter aortic valve implantation in a lung transplant recipient.

Transcatheter aortic valve implantation is a feasible therapeutic option for selected patients with severe aortic stenosis and high or prohibitive risk for standard surgery. Lung transplant recipients are often considered high-risk patients for heart surgery because of their specific transplant-associated characteristics and comorbidities. We report a case of successful transfemoral transcatheter aortic valve replacement in a lung transplant recipient with a symptomatic severe aortic stenosis, severe left ventricular dysfunction, and end-stage renal failure 9 years after bilateral lung transplantation.

Nutrition in cardiovascular disease: salt in hypertension and heart failure.

There is much evidence for a causal relationship between salt intake and blood pressure (BP). The current salt intake in many countries is between 9 and 12 g/day. A reduction in salt intake to the recommended level of 5-6 g/day lowers BP in both hypertensive and normotensive individuals. A further reduction to 3-4 g/day has a much greater effect. Prospective studies and outcome trials have demonstrated that a lower salt intake is associated with a decreased risk of cardiovascular disease. Increasing evidence also suggests that a high salt intake is directly related to left ventricular hypertrophy (LVH) independent of BP. Both raised BP and LVH are important risk factors for heart failure. It is therefore possible that a lower salt intake could prevent the development of heart failure. In patients who already have heart failure, a high salt intake aggravates the retention of salt and water, thereby exacerbating heart failure symptoms and progression of the disease. A lower salt intake plays an important role in the management of heart failure. Despite this, currently there is no clear evidence on how far salt intake should be reduced in heart failure. Our personal view is that these patients should reduce their salt intake to <5 g/day, i.e. the maximum intake recommended by the World Health Organisation for all adults. If salt intake is successfully reduced, there may well be a need for a reduction in diuretic dosage.

Pulmonary-artery pressure and exhaled nitric oxide in Bolivian and Caucasian high altitude dwellers.

There is evidence that high altitude populations may be better protected from hypoxic pulmonary hypertension than low altitude natives, but the underlying mechanism is incompletely understood. In Tibetans, increased pulmonary respiratory NO synthesis attenuates hypoxic pulmonary hypertension. It has been speculated that this mechanism may represent a generalized high altitude adaptation pattern, but direct evidence for this speculation is lacking. We therefore measured systolic pulmonary-artery pressure (Doppler chocardiography) and exhaled nitric oxide (NO) in 34 healthy, middle-aged Bolivian high altitude natives and in 34 age- and sex-matched, well-acclimatized Caucasian low altitude natives living at high altitude (3600 m). The mean+/-SD systolic right ventricular to right atrial pressure gradient (24.3+/-5.9 vs. 24.7+/-4.9 mmHg) and exhaled NO (19.2+/-7.2 vs. 22.5+/-9.5 ppb) were similar in Bolivians and Caucasians. There was no relationship between pulmonary-artery pressure and respiratory NO in the two groups. These findings provide no evidence that Bolivian high altitude natives are better protected from hypoxic pulmonary hypertension than Caucasian low altitude natives and suggest that attenuation of pulmonary hypertension by increased respiratory NO synthesis may not represent a universal adaptation pattern in highaltitude populations.

Respiratory nitric oxide and pulmonary artery pressure in children of aymara and European ancestry at high altitude.

Invasive studies suggest that healthy children living at high altitude display pulmonary hypertension, but the data to support this assumption are sparse. Nitric oxide (NO) synthesized by the respiratory epithelium regulates pulmonary artery pressure, and its synthesis was reported to be increased in Aymara high-altitude dwellers. We hypothesized that pulmonary artery pressure will be lower in Aymara children than in children of European ancestry at high altitude, and that this will be related to increased respiratory NO. We therefore compared pulmonary artery pressure and exhaled NO (a marker of respiratory epithelial NO synthesis) between large groups of healthy children of Aymara (n = 200; mean +/- SD age, 9.5 +/- 3.6 years) and European ancestry (n = 77) living at high altitude (3,600 to 4,000 m). We also studied a group of European children (n = 29) living at low altitude. The systolic right ventricular to right atrial pressure gradient in the Aymara children was normal, even though significantly higher than the gradient measured in European children at low altitude (22.5 +/- 6.1 mm Hg vs 17.7 +/- 3.1 mm Hg, p < 0.001). In children of European ancestry studied at high altitude, the pressure gradient was 33% higher than in the Aymara children (30.0 +/- 5.3 mm Hg vs 22.5 +/- 6.1 mm Hg, p < 0.0001). In contrast to what was expected, exhaled NO tended to be lower in Aymara children than in European children living at the same altitude (12.4 +/- 8.8 parts per billion [ppb] vs 16.1 +/- 11.1 ppb, p = 0.06) and was not related to pulmonary artery pressure in either group. Aymara children are protected from hypoxic pulmonary hypertension at high altitude. This protection does not appear to be related to increased respiratory NO synthesis.

Pulmonary-artery pressure and exhaled nitric oxide in bolivian and caucasian high altitude dwellers

Rapport de synthèse : Plusieurs études suggèrent que les populations vivant en haute altitude sont mieux protégées contre l'hypertension pulmonaire hypoxique que celles originaires de la plaine. Cependant, les mécanismes sous jacents ne sont pas bien compris. Chez les Tibétains, la synthèse augmentée par le système respiratoire de monoxyde d'azote (NO) atténue l'hypertension pulmonaire hypoxique. Il a été spéculé que ce mécanisme pourrait représenter un mode généralisé d'adaptation à la haute altitude, mais il n'existe pas de preuve directe qui consume cette hypothèse. Nous avons donc mesuré la pression artérielle pulmonaire (par échocardiographie Doppler) ainsi que la concentration du NO dans l'air exhalé chez 34 Boliviens en bonne santé, nés et ayant toujours vécus en haute altitude (3600 m) et chez 34 Caucasiens apparentés pour l'âge et le sexe, nés en basse altitude mais vivant depuis de nombreuses années à cette même haute altitude (3600 mètres). La pression artérielle pulmonaire (24.3±5.9 vs. 24.7±4.9 mm Hg) et le NO exhalé (19.2±7.2 vs. 22.5±9.5 ppb) étaient similaires chez les Boliviens et les Caucasiens. Il n'y avait aucune corrélation entre la pression artérielle pulmonaire et le NO respiratoire dans les deux groupes. Ces résultats ne fournissent donc aucune évidence que les Boliviens nés en haute altitude sont mieux protégés contre l'hypertension pulmonaire hypoxique que les Caucasiens nés à basse altitude. Cela suggère que l'atténuation de l'hypertension pulmonaire par une synthèse accrue de NO respiratoire ne représente pas un mode universel d'adaptation des populations à la haute altitude. Abstract : There is evidence that high altitude populations may be better protected from hypoxic pulmonary hypertension than low altitude natives, but the underlying mechanism is incompletely understood. In Tibetans, increased pulmonary respiratory NO synthesis attenuates hypoxic pulmonary hypertension. It has been speculated that this mechanism may represent a generalized high altitude adaptation pattern, but direct evidence for this speculation is lacking. We therefore measured systolic pulmonary-artery pressure (Doppler echocardiography) and exhaled nitric oxide (NO) in 34 healthy, middle-aged Bolivian high altitude natives and in 34 age- and sex-matched, well-acclimatized Caucasian low altitude natives living at high altitude (3600 m). The mean ± SD systolic right ventricular to right arterial pressure gradient (24.3 ± 5.9 vs. 24.7 ± 4.9 mmHg) and exhaled NO (19.2 ± 7.2 vs. 22.5 ± 9.5 ppb) were similar in Bolivians and Caucasians. There was no relationship between ,pulmonary-artery pressure and respiratory NO in the two groups. These findings provide no evidence that Bolivian high altitude natives are better protected from hypoxic pulmonary hypertension than Caucasian low altitude natives and suggest that attenuation of pulmonary hypertension by increased respiratory NO synthesis may not represent a universal adaptation pattern in highaltitude populations.

Exaggerated pulmonary hypertension during mild exercise in chronic mountain sickness.

BACKGROUND: Chronic mountain sickness (CMS) is an important public health problem and is characterized by exaggerated hypoxemia, erythrocytosis, and pulmonary hypertension. While pulmonary hypertension is a leading cause of morbidity and mortality in patients with CMS, it is relatively mild and its underlying mechanisms are not known. We speculated that during mild exercise associated with daily activities, pulmonary hypertension in CMS is much more pronounced. METHODS: We estimated pulmonary artery pressure by using echocardiography at rest and during mild bicycle exercise at 50 W in 30 male patients with CMS and 32 age-matched, healthy control subjects who were born and living at an altitude of 3,600 m. RESULTS: The modest, albeit significant difference of the systolic right-ventricular-to-right-atrial pressure gradient between patients with CMS and controls at rest (30.3 +/- 8.0 vs 25.4 +/- 4.5 mm Hg, P 5 .002) became more than three times larger during mild bicycle exercise (56.4 +/- 19.0 vs 39.8 +/- 8.0 mm Hg, P < .001). CONCLUSIONS: Measurements of pulmonary artery pressure at rest greatly underestimate pulmonary artery pressure during daily activity in patients with CMS. The marked pulmonary hypertension during mild exercise associated with daily activity may explain why this problem is a leading cause of morbidity and mortality in patients with CMS.

Assessment of systolic and diastolic LV function by MR myocardial tagging.

Heart failure has been divided into several different forms depending on etiology, clinical course and pathophysiology of left ventricular (LV) dysfunction. Systolic and diastolic dysfunction are characterized by a reduced cardiac output with normal (= diastolic dysfunction) or depressed (= systolic dysfunction) LV pump function. New diagnostic techniques such as magnetic resonance imaging (MRI) allow to determine noninvasively LV 3D motion by labelling specific myocardial regions (= myocardial "tagging") with a rectangular or radial grid. From the deformation of this grid rotational and translational motion of the heart can be derived. A "wringing" motion of the left ventricle has been described during systole which includes a clockwise rotation at the base and a counterclockwise rotation at the apex. During diastole, an "untwisting" motion has been demonstrated. In the normal heart, diastolic "untwisting" occurs primarily during isovolumic relaxation, analogous to the systolic "wringing" which takes place mainly during isovolumic contraction. A prolongation of the "untwisting" motion was found in the hypertrophied (aortic stenosis) and hibernating myocardium. Thus, heart failure is associated with profound alterations in the mechanical function of the heart which are manifested by changes in systolic "wringing" and diastolic "untwisting" motion.

Serum resistin concentrations and risk of new onset heart failure in older persons: the health, aging, and body composition (Health ABC) study.

OBJECTIVE: Resistin is associated with inflammation and insulin resistance and exerts direct effects on myocardial cells including hypertrophy and altered contraction. We investigated the association of serum resistin concentrations with risk for incident heart failure (HF) in humans. METHODS AND RESULTS: We studied 2902 older persons without prevalent HF (age, 73.6+/-2.9 years; 48.1% men; 58.8% white) enrolled in the Health, Aging, and Body Composition (Health ABC) Study. Correlation between baseline serum resistin concentrations (20.3+/-10.0 ng/mL) and clinical variables, biochemistry panel, markers of inflammation and insulin resistance, adipocytokines, and measures of adiposity was weak (all rho <0.25). During a median follow-up of 9.4 years, 341 participants (11.8%) developed HF. Resistin was strongly associated with risk for incident HF in Cox proportional hazards models controlling for clinical variables, biomarkers, and measures of adiposity (HR, 1.15 per 10.0 ng/mL in adjusted model; 95% CI, 1.05 to 1.27; P=0.003). Results were comparable across sex, race, diabetes mellitus, and prevalent and incident coronary heart disease subgroups. In participants with available left ventricular ejection fraction at HF diagnosis (265 of 341; 77.7%), association of resistin with HF risk was comparable for cases with reduced versus preserved ejection fraction. CONCLUSIONS: Serum resistin concentrations are independently associated with risk for incident HF in older persons.