Invasive Hemodynamic Assessment Research Articles

Heart failure with preserved ejection fraction; the other half of the heart failure, how it stands in 2013

Last two decade, heart failure with preserved ejection fraction was deprived from being considered as a part of spectrum of heart failure. May be heart failure with preserved ejection fraction was common but not recognized by cardiology fraternity. Heart failure with reduced ejection fraction and heart failure with preserved ejection fraction each make up about half of the overall heart failure burden. But the paradox is: morbidity and mortality in heart failure with preserved ejection fraction despite being similar to patients with heart failure with reduced ejection fraction, today’s cardiology community has not much to offer in terms of mortality reducing treatment. The term diastolic heart failure has been well replaced by heart failure with preserved ejection fraction because multiple non-diastolic abnormalities in cardiovascular function also contribute to heart failure with preserved ejection fraction and diastolic dysfunction always accompanied heart failure with reduced ejection fraction. Diagnosis of heart failure with preserved ejection fraction is an uphill task since it relies upon careful clinical evaluation, doppler (pulse wave and tissue) echocardiography, and invasive hemodynamic assessment after exclusion of potential noncardiac causes of symptoms suggestive of heart failure. Patients with heart failure with preserved ejection fraction are usually older women with a history of hypertension. Obesity, coronary artery disease, diabetes mellitus, and atrial fibrillation are also highly prevalent in heart failure with preserved ejection fraction. Cornerstone of treatment of this entity revolves around treatment of underlying cause and symptom guided therapy. Nepalese Heart Journal | Volume 10 | No.1 | November 2013| Pages 46-56 DOI: http://dx.doi.org/10.3126/njh.v10i1.9747

Ambulatory Hemodynamic Monitoring in the Management of Pulmonary Arterial Hypertension

Background: Pulmonary arterial hypertension (PAH) is characterized by pulmonary vascular remodeling, rise in pulmonary arterial pressures, and if left untreated, right heart failure. Invasive hemodynamic assessment with right heart catheterization (RHC) has been the gold standard for the diagnosis and serial assessment of patients with PAH. However, RHC has important limitations and might be supplemented by newer technologies in the management of PAH patients.Implications for Clinicians: Implantable hemodynamic monitors (IHM) hold the promise of being able to provide accurate pulmonary artery pressure measurements, with frequent or continuous remote monitoring in the home or ambulatory setting. As such, IHMs may provide a more complete understanding of a patient's hemodynamic profile and burden of disease. IHM data may also help to provide ongoing feedback in terms of a PAH patient's response to medical therapy and other interventions and might be valuable in specific subsets of patients with borderline or exercise-induced PAH.Conclusions: Though clinical studies using IHMs in PAH patients have been limited to small series and case reports, these devices hold a great deal of promise to supplement RHC in the management of PAH patients and warrant further investigation and clinical experience.

MRI Catheterization in Cardiopulmonary Disease

Diagnosis and prognostication in patients with complex cardiopulmonary disease can be a clinical challenge. A new procedure, MRI catheterization, involves invasive right-sided heart catheterization performed inside the MRI scanner using MRI instead of traditional radiographic fluoroscopic guidance. MRI catheterization combines simultaneous invasive hemodynamic and MRI functional assessment in a single radiation-free procedure. By combining both modalities, the many individual limitations of invasive catheterization and noninvasive imaging can be overcome, and additional clinical questions can be addressed. Today, MRI catheterization is a clinical reality in specialist centers in the United States and Europe. Advances in medical device design for the MRI environment will enable not only diagnostic but also interventional MRI procedures to be performed within the next few years.

Study design and rationale for investigating phosphodiesterase type 5 inhibition for the treatment of pulmonary hypertension due to chronic obstructive lung disease: the TADA-PHiLD (TADAlafil for Pulmonary Hypertension associated with chronic obstructive Lung Disease) trial.

In patients with chronic obstructive pulmonary disease (COPD), moderate or severe pulmonary hypertension (COPD-PH) is associated with increased rates of morbidity and mortality. Despite this, approaches to treatment and the efficacy of phosphodiesterase type 5 inhibition (PDE-5i) in COPD-PH are unresolved. We present the clinical rationale and study design to assess the effect of oral tadalafil on exercise capacity, cardiopulmonary hemodynamics, and clinical outcome measures in COPD-PH patients. Male and female patients 40-85 years old with GOLD stage 2 COPD or higher and pulmonary hypertension diagnosed on the basis of invasive cardiac hemodynamic assessment (mean pulmonary artery pressure [mPAP] >30 mmHg, pulmonary vascular resistance [PVR] >2.5 Wood units, and pulmonary capillary wedge pressure ≤18 mmHg at rest) will be randomized at a 1∶1 ratio to receive placebo or oral PDE-5i with tadalafil (40 mg daily for 12 months). The primary end point is change from baseline in 6-minute walk distance at 12 months. The secondary end points are change from baseline in PVR and mPAP at 6 months and change from baseline in peak volume of oxygen consumption ([Formula: see text]) during exercise at 12 months. Changes in systemic blood pressure and/or oxyhemoglobin saturation (Sao2) at rest and during exercise will function as safety outcome measures. TADA-PHiLD (TADAlafil for Pulmonary Hypertension assocIated with chronic obstructive Lung Disease) is the first sufficiently powered randomized clinical trial testing the effect of PDE-5i on key clinical and drug safety outcome measures in patients with at least moderate PH due to COPD.

Cardiac Magnetic Resonance Postcontrast T1 Time Is Associated With Outcome in Patients With Heart Failure and Preserved Ejection Fraction

The underlying pathophysiology of heart failure with preserved ejection fraction (HFPEF) is incompletely understood, but myocardial extracellular matrix accumulation is thought to play a major role. Our aims were to estimate myocardial extracellular matrix using cardiac magnetic resonance T1 mapping and to assess the relationship between pathobiology/pathophysiology and prognosis. Patients with suspected HFPEF (n=100) were enrolled in this prospective, observational study. Confirmatory diagnostic tests, cardiac magnetic resonance imaging including T1 mapping, and invasive hemodynamic assessments were performed at baseline. Sixty-one patients with confirmed HFPEF entered a longitudinal outcome-monitoring phase (mean, 22.9±5.0 months), during which 16 had a cardiac event. Cardiac magnetic resonance T1 time (hazard ratio, 0.99; 95% confidence interval, 0.98-0.99; P=0.046), left atrial area (hazard ratio, 1.08; 95% confidence interval, 1.03-1.13; P<0.01), and pulmonary vascular resistance (hazard ratio, 1.01; 95% confidence interval, 1.00-1.01; P=0.03) were significantly associated with cardiac events. Patients with T1 times below the median (<388.3 ms) were at greater risk of cardiac events than the rest of the group (P<0.01). Extracellular matrix of left ventricular biopsies (n=9), quantified by TissueFAXS technology correlated with T1 time (R=0.98; P<0.01). T1 time also correlated with right ventricular-pulmonary arterial coupling (pulmonary vascular resistance: R=-0.36; P<0.01; right ventricular ejection fraction: R=0.28; P=0.01). In the present preliminary study, cardiac magnetic resonance postcontrast T1 time is associated with prognosis in HFPEF, suggesting postcontrast T1 as possible biomarker for HFPEF.

Enhancing the accuracy of echocardiography in the diagnosis of pulmonary arterial hypertension

Although routine use of Doppler echocardiography has led to an increased recognition of pulmonary hypertension, the role of Doppler echocardiography has largely remained as a screening tool with the primary emphasis on the presence or absence of an increased Doppler-estimated pulmonary artery systolic pressure (PASP). However, the utility of Doppler echocardiography in the workup of pulmonary hypertension extends far beyond that of a screening tool, with the integration of relevant Doppler echocardiography parameters providing a wealth of hemodynamic insight into not only if a patient has pulmonary hypertension, but why they have pulmonary hypertension. This review summarizes some of the recent advances in the use of Doppler echocardiography in evaluating the pathophysiology of pulmonary hypertension. Distinguishing pulmonary hypertension related to pulmonary vascular disease (i.e. pulmonary arterial hypertension, pulmonary hypertension due to lung disease, or chronic thromboembolic pulmonary hypertension; PHPVD), from those with left heart disease associated pulmonary hypertension (pulmonary venous hypertension; PVH) is crucial as workup and treatment options differ dramatically. Recent studies have identified easily obtainable Doppler echocardiography parameters that can reliably distinguish between PHPVD and PVH, allowing for rapid triage of patients with evidence of PHPVD to invasive right heart catheterization whiles avoiding invasive investigation and the inappropriate use of pulmonary hypertension specific therapy in patients with PVH. This review highlights the importance of integrating two-dimensional and Doppler parameters in order to inform the clinician as to the hemodynamic cause of pulmonary hypertension, thus enhancing the diagnostic accuracy of Doppler echocardiography, rapidly identifying those with PHPVD and right heart dysfunction and assisting in triage of patients to further invasive hemodynamic assessment.

The role of invasive hemodynamic assessment during Mitra-Clip™ implantation

Percutaneous mitral valve repair with the implantation of the Mitra-Clip™ device (Abbott Vascular-Evalve, Menlo Park, CA) is a promising technique for the transcatheter management of high-risk surgical patients with symptomatic severe mitral regurgitation (MR). Its safety and efficacy have been demonstrated by the EVEREST I and II trials, registries and case series.

Echocardiographic and Hemodynamic Predictors of Mortality in Idiopathic Pulmonary Fibrosis

Idiopathic pulmonary fibrosis (IPF) can lead to the development of pulmonary hypertension, which is associated with an increased risk of death. In pulmonary arterial hypertension, survival is directly related to the capacity of the right ventricle to adapt to elevated pulmonary vascular load. The relative importance of right ventricular function in IPF is not well understood. Our objective was to evaluate right ventricular echocardiographic and hemodynamic predictors of mortality in a cohort of patients with IPF referred for lung transplant evaluation. We performed a retrospective cohort study of 135 patients who met 2011 American Thoracic Society/European Respiratory Society criteria for IPF and who were evaluated for lung transplantation at the Hospital of the University of Pennsylvania. Right ventricle:left ventricle diameter ratio (hazard ratio [HR], 4.5; 95% CI, 1.7-11.9), moderate to severe right atrial and right ventricular dilation (HR, 2.9; 95% CI, 1.4-5.9; and HR, 2.7; 95% CI, 1.4-5.4, respectively) and right ventricular dysfunction (HR, 5.5; 95% CI, 2.6-11.5) were associated with an increased risk of death. Higher pulmonary vascular resistance was also associated with increased mortality (HR per 1 Wood unit, 1.3; 95% CI, 1.1-1.5). These risk factors were independent of age, sex, race, height, weight, FVC, and lung transplantation status. Other hemodynamic indices, such as mean pulmonary artery pressure and cardiac index, were not associated with outcome. Right-sided heart size and right ventricular dysfunction measured by echocardiography and higher pulmonary vascular resistance by invasive hemodynamic assessment predict mortality in patients with IPF evaluated for lung transplantation.

Pulmonary arterial hypertension

Pulmonary arterial hypertension (PAH) is a chronic and progressive disease leading to right heart failure and ultimately death if untreated. The first classification of PH was proposed in 1973. In 2008, the fourth World Symposium on PH held in Dana Point (California, USA) revised previous classifications. Currently, PH is devided into five subgroups. Group 1 includes patients suffering from idiopathic or familial PAH with or without germline mutations. Patients with a diagnosis of PAH should systematically been screened regarding to underlying mutations of BMPR2 gene (bone morphogenetic protein receptor type 2) or more rarely of ACVRL1 (activine receptor-like kinase type 1), ENG (endogline) or Smad8 genes. Pulmonary veno occusive disease and pulmonary capillary hemagiomatosis are individualized and designated as clinical group 1'. Group 2 'Pulmonary hypertension due to left heart diseases' is divided into three sub-groups: systolic dysfonction, diastolic dysfonction and valvular dysfonction. Group 3 'Pulmonary hypertension due to respiratory diseases' includes a heterogenous subgroup of respiratory diseases like PH due to pulmonary fibrosis, COPD, lung emphysema or interstitial lung disease for exemple. Group 4 includes chronic thromboembolic pulmonary hypertension without any distinction of proximal or distal forms. Group 5 regroup PH patients with unclear multifactorial mechanisms. Invasive hemodynamic assessment with right heart catheterization is requested to confirm the definite diagnosis of PH showing a resting mean pulmonary artery pressure (mPAP) of ≥ 25 mmHg and a normal pulmonary capillary wedge pressure (PCWP) of ≤ 15 mmHg. The assessment of PCWP may allow the distinction between pre-capillary and post-capillary PH (PCWP > 15 mmHg). Echocardiography is an important tool in the management of patients with underlying suspicion of PH. The European Society of Cardiology and the European Respiratory Society (ESC-ERS) guidelines specify its role, essentially in the screening proposing criteria for estimating the presence of PH mainly based on tricuspid regurgitation peak velocity and systolic artery pressure (sPAP). The therapy of PAH consists of non-specific drugs including oral anticoagulation and diuretics as well as PAH specific therapy. Diuretics are one of the most important treatment in the setting of PH because right heart failure leads to fluid retention, hepatic congestion, ascites and peripheral edema. Current recommendations propose oral anticoagulation aiming for targeting an International Normalized Ratio (INR) between 1.5-2.5. Target INR for patients displaying chronic thromboembolic PH is between 2–3. Better understanding in pathophysiological mechanisms of PH over the past quarter of a century has led to the development of medical therapeutics, even though no cure for PAH exists. Several specific therapeutic agents were developed for the medical management of PAH including prostanoids (epoprostenol, trepoprostenil, iloprost), endothelin receptor antagonists (bosentan, ambrisentan) and phosphodiesterase type 5 inhibitors (sildenafil, tadalafil). This review discusses the current state of art regarding to epidemiologic aspects of PH, diagnostic approaches and the current classification of PH. In addition, currently available specific PAH therapy is discussed as well as future treatments.

Cardiac output response to exercise in relation to metabolic demand in heart failure with preserved ejection fraction

Exercise intolerance is a hallmark of heart failure with preserved ejection fraction (HFpEF), yet its mechanisms remain unclear. The current study sought to determine whether increases in cardiac output (CO) during exercise are appropriately matched to metabolic demands in HFpEF. Patients with HFpEF (n = 109) and controls (n = 73) exercised to volitional fatigue with simultaneous invasive (n = 96) or non-invasive (n = 86) haemodynamic assessment and expired gas analysis to determine oxygen consumption (VO2) during upright or supine exercise. At rest, HFpEF patients had higher LV filling pressures but similar heart rate, stroke volume, EF, and CO. During supine and upright exercise, HFpEF patients displayed lower peak VO2 coupled with blunted increases in heart rate, stroke volume, EF, and CO compared with controls. LV filling pressures increased dramatically in HFpEF patients, with secondary elevation in pulmonary artery pressures. Reduced peak VO2 in HFpEF patients was predominantly attributable to CO limitation, as the slope of the increase in CO relative to VO2 was 20% lower in HFpEF patients (5.9 ± 2.5 vs. 7.4 ± 2.6 L blood/L O2, P = 0.0005). While absolute increases in arterial-venous O2 difference with exercise were similar in HFpEF patients and controls, augmentation in arterial-venous O2 difference relative to VO2 was greater in HFpEF patients (8.9 ± 3.4 vs. 5.5 ± 2.0 min/dL, P < 0.0001). These differences were observed in the total cohort and when upright and supine exercise modalities were examined individually. While diastolic dysfunction promotes congestion and pulmonary hypertension with stress in HFpEF, reduction in exercise capacity is predominantly related to inadequate CO relative to metabolic needs.

Integration of exercise evaluation into the algorithm for evaluation of patients with suspected heart failure with preserved ejection fraction

Approximately half of all patients with heart failure (HF) have a preserved left ventricular ejection fraction (HFPEF) and the prevalence of this form of HF is increasing. Although dyspnoea on exertion and diminished functional capacity is the key symptom of patients with HFPEF, current diagnostic criteria focus on resting indices of ventricular function. Specifically, current proposed criteria for the diagnosis of HFPEF, include clinical signs of HF; normal left ventricular systolic function; and evidence of abnormal diastolic performance and/or altered natriuretic peptides. By contrast, recent studies demonstrate that the key pathophysiologic features of HFPEF may not be evident at rest, and can only be detected during exertion. This review addresses the potential role of exercise testing using invasive haemodynamic or echocardiographic assessment in patients with suspected HFPEF in which current diagnostic criteria are not met.

Critical reappraisal of pulmonary artery catheterization and invasive hemodynamic assessment in acute heart failure

Use of the pulmonary artery catheter (PAC) in the management of heart failure has declined precipitously despite guideline-supported indications, especially among patients hospitalized with acute heart failure (HF) syndromes. Here, the authors critically review the current role of the PAC and the management of patients with HF, and discuss the role of the PAC in the development of new therapies for HF. Pulmonary artery catheterization is a safe procedure when performed by experienced operators, and invasive hemodynamic evaluation with the PAC is recommended in select clinical settings. The PAC may have a unique role in identifying high-risk HF patients with persistent hemodynamic abnormalities during hospitalization. Early-phase trials of novel therapies to improve outcomes in patients with acute HF should include an assessment of hemodynamic effects utilizing the PAC. Once therapies that are effective in improving outcomes are available, the PAC might be a useful or necessary tool in the initiation and titration of such treatments and improved outcomes from PAC guided therapy may be demonstrated. Adequate training and experience are required to successfully use the PAC to minimize complications, ensure proper data collection and appropriate decision-making. Improved education and guidelines are required to ensure continued safe and appropriate contemporary use of the PAC.

Clinical Characteristics and Outcomes in Patients with Mismatched Filling Pressures in Advanced Heart Failure: Looking beyond the JVP

Purpose Right atrial (RA) and pulmonary capillary wedge pressure (PCWP) are concordant in the majority of heart failure (HF) patients, allowing estimation of volume status by jugular venous pressure (JVP). Pts with discordant filling pressures have been identified while undergoing transplant evaluation. However, the incidence and outcomes of discordant filling pressures have not been evaluated in pts with chronic advanced HF. Methods and Materials The MEDAMACS screening pilot was a multicenter, prospective, observational study of pts with advanced systolic HF, including 116 pts who underwent right heart catheterization (RHC) within 6 months of enrollment. Three strata were defined: 1. Matched high (MH, RA≥11mmHg +PCWP≥20mmHg) 2. Matched low (ML, RA≤10 mmHg+PCWP≤19mmHg) or 3. Mismatched (MM i.e. RA≤10 mmHg+PCWP≥20mmHg). Pts were assessed for outcomes of death, initiation of inotropes, mechanical circulatory support, or transplant. Results Of the 116 pts in this analysis, 25%, 47%, and 28% pts were in the ML, MH and MM groups respectively. 49 events were recorded by 6 months. The majority of pts with in the MM group had low RA pressure and high PCWP. There were no differences between the 3 groups in baseline demographics, HF etiology, EF, or NYHA class. The MH and MM groups included fewer pts tolerating ACE-inhibitors (ML 76%, MH 50%, MM 58%, p=0.07), and mean Cr was higher in the MM group (ML 1.3 mmol/L, MH 1.6mmol/L, MM 1.8mmol/L, p= 0.02). Six-month event free survival was 75%, 67% and 55% for the ML, MH and MM groups respectively (p=0.249). Conclusions Discordant filling pressures were found in 28% of advanced HF patients on medical therapy and were associated with impaired renal function and lower tolerance of neurohormonal antagonists. Despite limited evidence of congestion by JVP assessment, event rates are high for pts with discordant filling pressures, affirming a role for selective use of invasive hemodynamic assessment in this population.

The 2013 International Society for Heart and Lung Transplantation Guidelines for mechanical circulatory support: Executive summary

Institutional Affiliations Co-chairs Feldman D: Minneapolis Heart Institute, Minneapolis, Minnesota, Georgia Institute of Technology and Morehouse School of Medicine; Pamboukian SV: University of Alabama at Birmingham, Birmingham, Alabama; Teuteberg JJ: University of Pittsburgh, Pittsburgh, Pennsylvania Task force chairs Birks E: University of Louisville, Louisville, Kentucky; Lietz K: Loyola University, Chicago, Maywood, Illinois; Moore SA: Massachusetts General Hospital, Boston, Massachusetts; Morgan JA: Henry Ford Hospital, Detroit, Michigan Contributing writers Arabia F: Mayo Clinic Arizona, Phoenix, Arizona; Bauman ME: University of Alberta, Alberta, Canada; Buchholz HW: University of Alberta, Stollery Children’s Hospital and Mazankowski Alberta Heart Institute, Edmonton, Alberta, Canada; Deng M: University of California at Los Angeles, Los Angeles, California; Dickstein ML: Columbia University, New York, New York; El-Banayosy A: Penn State Milton S. Hershey Medical Center, Hershey, Pennsylvania; Elliot T: Inova Fairfax, Falls Church, Virginia; Goldstein DJ: Montefiore Medical Center, New York, New York; Grady KL: Northwestern University, Chicago, Illinois; Jones K: Alfred Hospital, Melbourne, Australia; Hryniewicz K: Minneapolis Heart Institute, Minneapolis, Minnesota; John R: University of Minnesota, Minneapolis, Minnesota; Kaan A: St. Paul’s Hospital, Vancouver, British Columbia, Canada; Kusne S: Mayo Clinic Arizona, Phoenix, Arizona; Loebe M: Methodist Hospital, Houston, Texas; Massicotte P: University of Alberta, Stollery Children’s Hospital, Edmonton, Alberta, Canada; Moazami N: Minneapolis Heart Institute, Minneapolis, Minnesota; Mohacsi P: University Hospital, Bern, Switzerland; Mooney M: Sentara Norfolk, Virginia Beach, Virginia; Nelson T: Mayo Clinic Arizona, Phoenix, Arizona; Pagani F: University of Michigan, Ann Arbor, Michigan; Perry W: Integris Baptist Health Care, Oklahoma City, Oklahoma; Potapov EV: Deutsches Herzzentrum Berlin, Berlin, Germany; Rame JE: University of Pennsylvania, Philadelphia, Pennsylvania; Russell SD: Johns Hopkins, Baltimore, Maryland; Sorensen EN: University of Maryland, Baltimore, Maryland; Sun B: Minneapolis Heart Institute, Minneapolis, Minnesota; Strueber M: Hannover Medical School, Hanover, Germany Independent reviewers Mangi AA: Yale University School of Medicine, New Haven, Connecticut; Petty MG: University of Minnesota Medical Center, Fairview, Minneapolis, Minnesota; Rogers J: Duke University Medical Center, Durham, North Carolina

A novel porcine model of early left ventricular dysfunction for translational research

A novel porcine model of early left ventricular dysfunction for translational research Nadim Malik, Kelly A Farrell, Sarah B Withers, Elizabeth J Wright, Cathy M HoltInstitute for Cardiovascular Science, University of Manchester, Manchester, United KingdomBackground: The early stages of left ventricular (LV) dysfunction account for a much larger proportion of the population with heart disease than that with clinical heart failure. However, LV dysfunction is more difficult to diagnose than established heart failure, and because of this it is not usually treated. Research on LV dysfunction is commonly conducted in small animal models in which the cardiac pathophysiology is dissimilar to that in humans, thereby restricting translation. This study aimed to use a novel pig model of mild to moderate early ischemic LV dysfunction to assess the effects of such dysfunction in the myocardium.Methods: Multiple areas of controlled microinfarcts were created via microembolization using embolization beads, with invasive hemodynamic and transthoracic echocardiographic assessment of LV function. Four weeks after intervention, the hearts were explanted for determination of the infarcted surface area and analysis of calcium regulatory proteins.Results: In vivo hemodynamic measurements confirmed a &gt;25% decrease in LV dP/dt (maximum and minimum) with creation of microinfarcts compared with baseline, whilst echocardiography showed mild to moderate LV dysfunction. Perioperative mortality was 10%&ndash;15%. In surviving pigs, morphometry at 4 weeks confirmed that up to 20% of the total LV surface area contained microinfarcts. Western blot analysis showed alterations in levels of the calcium regulatory proteins, sarcoplasmic reticulum Ca2+ ATPase and sodium-calcium exchange, in infarcted areas, compared with normal LV tissue from the same animals.Conclusion: These results demonstrate the usefulness of this model for investigation of the precise molecular and cellular changes associated with early mild to moderate LV dysfunction from ischemic injury, and its potential use for modulating these changes with the aim of achieving functional reversibility or regeneration of the myocardium.Keywords: left ventricular dysfunction, heart failure, porcine model

Abstract 9927: Helix B Surface Peptide, a Small Non-erythropoietic Molecule Based on the Erythropoietin Structure, Effectively Ameliorates the Progression of Chronic Heart Failure in the Rat Post Myocardial Infarction Model

The cardioprotective properties of Erythropoietin (EPO) are well documented in pre-clinical studies. However, due to its erythropoietic and prothrombotic properties, the EPO treatment cannot be used in chronic heart failure (CHF), unless indicated by accompanied anemia. Helix B surface peptide (HBSP), a small peptide synthetized on the basis of EPO molecule (ARA290, Araim Pharmaceutical), does not stimulate erythropoiesis. We have reported similarly strong cardioprotective effects of HBSP and EPO in the rat model of myocardial infarction (MI). In this study, we tested the effect of long-term treatment with HBSP on mortality and cardiac remodeling in post-MI CHF in rats. For the 10 months, starting two weeks after left coronary artery ligation, rats received the i.p. injections of HBSP (60µg/kg; n=33) or saline (n=33) 2 times per week. Compared to saline-treated rats, HBSP treatment significantly reduced mortality (35% vs. 65%; p&lt;0.05). Repeated Echocardiography demonstrated remarkable attenuation of left ventricular (LV) chamber dilatation (EDV: 41% vs. 86%; ESV: 44% vs. 135%; p&lt;0.05), LV functional deterioration (EF: -4% vs. -63%; p&lt;0.05) and MI expansion (3% vs. 38%; p&lt;0.05) in HPSP-treated rats compared to saline-treated rats. Blood hematocrit level measured monthly was not affected by HBSP treatment. An invasive hemodynamic assessment at the end of 10-mo treatment showed better LV systolic function (PRSW: 63±5 vs. 40±4; p&lt;0.05) and Arterio-ventricular coupling (Ea/Ees: 1.2±0.2 vs. 2.7±0.7; p&lt;0.05) in HBSP-treated rats compared to saline-treated rats. Histological analysis revealed less apoptosis (0.6±0.1% vs. 0.9±0.1%; p&lt;0.05), myocardial fibrosis (2.6±0.2% vs. 4.1±0.5%; p&lt;0.05), and myocyte hypertrophy (cell diameter: 31±1µm vs. 37±1µm; p&lt;0.05) in non-infarcted myocardium among HBSP-treated rats compared to saline-treated rats. Results suggest that HBSP could be considered as a safe alternative to EPO for a further clinical testing in the patients with chronic heart failure.

Comparison between adenosine and isoflurane for assessing the coronary flow reserve in mouse models of left ventricular pressure and volume overload

Adenosine and high-concentration isoflurane are commonly used to induce hyperemia for assessment of coronary flow reserve (CFR) in mice, but high-concentration isoflurane may exacerbate cardiac dysfunction, leading to impaired CFR. However, there is no study be found comparing the effects of adenosine and isoflurane on CFR and corresponding cardiac function. High-resolution echocardiography and invasive hemodynamic assessment were performed in 20 mice 2 wk after transverse aortic constriction (TAC), aortic regurgitation (AR), and corresponding sham operation. CFR was calculated as the ratio of hyperemic to basal peak diastolic velocity (CFRpdv) or diastolic velocity-time integral (CFRdvti). In the sham-operated mice, no differences were observed between the effects of adenosine and isoflurane on CFR, left ventricular systolic function (left ventricular ejection fraction and fractional shortening), left ventricular end-systolic pressure, maximal contraction and relaxation velocity (+dp/dt and -dp/dt), alteration of left ventricular pressure (ΔLVP), or ±dp/dt (Δdp/dt). But adenosine-derived results were significantly higher than isoflurane-derived ones in both the TAC and the AR groups. Moreover, CFRpdv or CFRdvti was positively correlated with both LVEF and LVFS. Compared with adenosine-derived CFR, isoflurane-derived CFR may be underestimated in the TAC and the AR mice, which is probably associated with suppressed cardiac function.

Blood Urea Nitrogen to Creatinine Ratio Does not Predict Intravasular Volume Status in Patients With Heart Failure

In patients who are treated with diuretics, blood urea nitrogen (BUN) to serum creatinine (Scr) ratio is frequently used to evaluate intravascular volume status. We aimed to investigate the correlation between BUN to Scr ratio and invasive hemodynamic assessment of intravascular volume status. Data from patients who underwent right heart catheterization (RHC) at our center from 2008 to 2011 were reviewed. We obtained BUN, Scr and BUN to Scr ratio from Lab collected within 24 hour from the RHC. We obtained right atria (RA) pressure and pulmonary capillary wedge pressure from the RHC. A total of 501 patients were included in the analysis. 213 patients had BUN/Cr ratio more than 20. There was no correlation between high BUN to Scr ratio with RA pressure. Linear regression analysis was used, adjusted R-squared = 0.0157. High BUN to Scr ratio did not predict intravascular volume status in our population, and this could be due to rapid diuresis, and diuretics therapy in patients with symptomatic heart failure should not be based on this ratio.

Hemodynamics in the Cardiac Catheterization Laboratory of the 21st Century

There has been a striking evolution in the role of the cardiac catheterization laboratory over the past decades.1 In the 1950s and 1960s, hemodynamic assessment in the cardiac catheterization laboratory was essential for understanding the physiology and pathophysiology of patients with cardiovascular diseases. With the development of surgical interventions to treat patients with valvular and congenital heart disease, it became necessary for the cardiac catheterization laboratory to provide an accurate hemodynamic assessment, laying out a therapeutic road map. Nearly all patients who had open heart surgery underwent a complete hemodynamic catheterization before surgery. In the 1980s and 1990s, the evolution of 2-dimensional echocardiography and Doppler echocardiography provided an alternative noninvasive approach for the assessment of both cardiac anatomy and hemodynamics in patients with structural heart disease.2 By measuring blood flow velocities noninvasively, Doppler echocardiography was able to provide information on volumetric flow, intracardiac pressures, pressure gradients, and valve areas, as well as diastolic filling of the heart. Furthermore, noninvasive studies could be repeated easily, allowing the practitioner to follow the progress of his/her patient's condition longitudinally. At the same time, there was growing emphasis on coronary angiography for defining epicardial coronary disease with the subsequent development of interventional approaches for coronary disease with catheter-based therapies. As the major focus in the catheterization laboratory shifted to the diagnosis and treatment of the patient with acute and chronic coronary artery disease, the hemodynamic assessment of patients with structural heart disease was left to the noninvasive echocardiographic laboratory. As a consequence, many cardiac catheterization laboratories provided neither the training nor the expertise to assess hemodynamics properly. However, the advent of procedures such as balloon valvotomy, percutaneous valve implantation, and septal ablation has revived interest in structural heart disease and provided the invasive cardiologist with an armamentarium to treat patients who previously …

Repairing chronic myocardial infarction with autologous mesenchymal stem cells engineered tissue in rat promotes angiogenesis and limits ventricular remodeling

BackgroundTissue engineering scaffold constitutes a new strategy of myocardial repair. Here, we studied the contribution of a patch using autologous mesenchymal stem cells (MSCs) seeded on collagen-1 scaffold on the cardiac reconstruction in rat model of chronic myocardial infarction (MI).MethodsPatches were cultured with controlled MSCs (growth, phenotype and potentiality). Twenty coronary ligated rats with tomoscingraphy (SPECT)-authenticated transmural chronic MI were referred into a control group (n = 10) and a treated group (n = 10) which beneficiated an epicardial MSC-patch engraftment. Contribution of MSC-patch was tested 1-mo after using non-invasive SPECT cardiac imaging, invasive hemodynamic assessment and immunohistochemistry.Results3D-collagen environment affected the cell growth but not the cell phenotype and potentiality. MSC-patch integrates well the epicardial side of chronic MI scar. In treated rats, one-month SPECT data have documented an improvement of perfusion in MI segments compared to control (64 ± 4% vs 49 ± 3% p = 0.02) and a reduced infarction. Contractile parameter dp/dtmax and dp/dtmin were improved (p & 0.01). Histology showed an increase of ventricular wall thickness (1.75 ± 0.24 vs 1.35 ± 0.32 mm, p &0.05) and immunochemistry of the repaired tissue displayed enhanced angiogenesis and myofibroblast-like tissue.Conclusion3D-MSC-collagen epicardial patch engraftment contributes to reverse remodeling of chronic MI.