Andrea's story

First-hand accounts of illness experiences provide important insights for other patients and their carers and can be a powerful tool for patient information and professional education. Andrea was ran over by a motor-bike while he was carried by bike and reported a complicated femur fracture. Three different representations of the story are reported and confronted: the bold chronicle of events, that sets the scenery and time sequence; Andrea's mother point of view on what happened after the accident, and during the course of the illness; and Andrea's story, told with his words and drawings. The methodological comments offered as discussion, stress how the collection of relevant patients stories can be a valuable research resource because it can offer a broad perspective which cannot be obtained by other means.     

Eplerenone, a selective aldosterone blocker, improves diastolic function in aged rats with small-to-moderate myocardial infarction

BACKGROUND: The incidence of cardiovascular diseases increases rapidly with age, and the elderly suffer higher morbidity and mortality. Aldosterone blockers have shown benefits in patients with left ventricular (LV) dysfunction and heart failure after myocardial infarction (MI). However, aldosterone blockade efficacy has not been explored in aged animals with MI.Methods and results Small-to-moderate MI was induced by coronary artery ligation in 16-month old rats, divided into 3 groups: sham-operated (control, n = 9), MI (n = 9), and MI fed a diet containing eplerenone (120 mg/kg/day, MI+Eplerenone, n = 9) given 18 days postsurgery and up to sacrifice 3 months later. At sacrifice, untreated MI rats did not show overt systolic dysfunction but they had (1) echocardiographic evidences of impaired relaxation (increase of E wave deceleration time and of isovolumic relaxation time, decrease of peak E wave velocity), (2) hemodynamically impaired LV relaxation (LV -dP/dt from 7413 +/- 720 to 4956 +/- 475 mm Hg/s, P < .05), and (3) significant increase of collagen content in LV interstitium (from 4.27 +/- 0.23 to 5.34 +/- 0.24%, P < .01) and in aorta (from 19 +/- 1 to 24 +/- 2%, P < .05). Eplerenone normalized echocardiographic and hemodynamic evidences of diastolic dysfunction, as well as myocardial interstitial collagen and aortic fibrosis (all parameters statistically different from untreated MI). CONCLUSION: In aged rats with small to moderate MI, eplerenone normalized diastolic relaxation, possibly through a reduction of interstitial fibrosis.     

Quality assessment and quality control of echocardiographic performance in a large multicenter international study: Valsartan in heart failure trial (Val-HeFT).

OBJECTIVE: To qualify 302 multinational echocardiography sites to record and read serial studies and to monitor quality in 5010 patients randomized into Valsartan in Heart Failure Trial (Val-HeFT). BACKGROUND: Decentralized echocardiography reading is unprecedented in large clinical trials. METHODS: Single and duplicate recordings, and triplicate readings of echocardiographic variables were submitted to 3 core laboratories. Quality of recording was defined with a 16-point scoring system; accuracy of reading by agreement with core readings; reproducibility by agreement between the duplicate studies. RESULTS: Seventy-five percent of initial submissions were approved for recording, and 50% for reading. Resubmissions were evaluated until approval. Initial scores of sites approved with 1 versus 2 submissions differed, 13.8 +/- 1.4 versus 10.6 +/- 2.0, P <.001; final score was similar, 13.4 +/- 1.6, P = ns. Initial score of sites approved after 3 or more submissions differed, 9.5 +/- 1.9, P <.001; final score improved to 12.7 +/- 1.9, but remained lower, P <.001. Expressed as 95% limits of agreement (mean difference +/- 1.96 x SD), accuracy = -0.04 +/- 0.74 cm for left ventricular internal end-diastolic diameter (LVIDd); -0.29 +/- 14.3% for ejection fraction (EF); reproducibility = 0.00 +/- 0.53 cm for LVIDd; -0.25 +/- 8.3% for EF. Quality of random sampling at baseline, 4, 12, and 18 months showed recording scores of 11.7 +/- 2.7, 12.3 +/- 2.4, 12.1 +/- 2.2, and 11.4 +/- 2.0, P =.24. Power analysis revealed differences of 0.09 cm for LVIDd, and 0.86% for EF detectable with a power of 90% and alpha of 5%. CONCLUSION: The qualifying process improved echocardiography recording and reading to bring 95% of the sites to an equivalent level of quality. Monitoring quality found that recording quality and reading accuracy were maintained 18 months into the trial. Reproducibility, given the large sample size, will be able to detect small changes in LVIDd and EF.     

Signs and symptoms in chronic heart failure: relevance of clinical trial results to point of care-data from Val-HeFT

BACKGROUND: Clinical trials emphasize mortality and morbidity endpoints. AIMS: To bring relevance of trial results to point of care by examining the prognostic and therapeutic value of individual signs and symptoms (S&S). METHODS: We analysed data from 5010 patients with stable chronic heart failure and left ventricular dysfunction who were participants in the Val-HeFT study. Individual S&S were stratified by severity. Treatment differences between valsartan and placebo were analysed by S&S strata at baseline and endpoint by logistical regression, and an overall S&S score by ANCOVA. Hazard ratios of S&S strata were calculated for mortality and heart failure hospitalisation. Prognostic contributions of S&S to other variables were determined by multivariate analysis. RESULTS: At endpoint, there were significantly fewer valsartan and more placebo patients with severe symptoms. Over time, improvement in the S&S overall score was significantly more favourable for valsartan than placebo. S&S strata were significantly predictive of risk for hospitalisation and death. S&S were each independent and incremental predictors of mortality compared to other variables. Symptom strata separated out moderately symptomatic patients with a mortality rate which was intermediate between that for NYHA Class II and III. CONCLUSION: Risk stratification of individual S&S defined prognosis, identified patients with an intermediate mortality between Class II and III, and treatment benefits of valsartan over placebo.     

Incremental prognostic value of changes in B-type natriuretic peptide in heart failure

Purpose

B-type natriuretic peptide is one of the most sensitive and specific biohumoral markers of heart failure. We hypothesized that B-type natriuretic peptide changes during treatment of heart failure may provide independent information on disease progression and outcome in patients enrolled in the Val-HeFT trial.

Methods

Patients were divided into four groups according to concentrations of B-type natriuretic peptide at baseline versus 4 months (n = 3740) or 12 months (n = 3343), with respect to the baseline median (97 pg/mL): low→low (stable below median, 44%-46%), high→high (stable above median, 32%-37%), high→low (above to below median, 12%-14%), and low→high (below to above median, 6%-9%). Cox multivariate regression analysis was used to assess the risk of death and morbidity, with adjustment for baseline B-type natriuretic peptide concentrations.

Results

Patients who improved their B-type natriuretic peptide at 4 months (high→low) had a similar risk for mortality (hazard ratio = 1.191, 95% confidence interval [CI] 0.870-1.631, P =.2746) compared with the low→low patients. Conversely, patients who worsened in their B-type natriuretic peptide (low→high) had a risk for mortality (hazard ratio 2.578, CI, 1.861-3.571, P <.0001) higher than patients in the low→low group, and indistinguishable from the high→high group. Worsening of B-type natriuretic peptide (low→high) was associated with 0.03 cm/m² increase in left ventricular end-diastolic diameter, whereas it decreased by 0.10 cm/m² in high→low and low→low groups (P <.001).

Conclusions

Changes in B-type natriuretic peptide over time with respect to a threshold value of 97 pg/mL convey an independent and additional prognostic value compared with a single determination of B-type natriuretic peptide in a large population of patients with chronic symptomatic heart failure and might be helpful in the management of these patients.     

Circulating cardiovascular biomarkers in recurrent atrial fibrillation: data from the GISSI-atrial fibrillation trial

Abstract. Latini R, Masson S, Pirelli S, Barlera S, Pulitano G, Carbonieri E, Gulizia M, Vago T, Favero C, Zdunek D, Struck J, Staszewsky L, Maggioni AP, Franzosi MG, Disertori M on the behalf of the GISSI‐AF Investigators (Istituto di Ricerche Farmacologiche “Mario Negri”, Milan; Istituti Ospitalieri, Cremona; POL Madonna della Consolazione, Reggio Calabria; Ospedale Nuovo Girolimo Fracastoro, San Bonifacio; Ospedale Garibaldi‐Nesima, Catania; Ospedale Luigi Sacco, Milan, Italy; Roche Diagnostics, Rotkreuz, Switzerland; B.R.A.H.M.S. AG, Henningsdorf, Germany; ANMCO Research Center, Florence; and Ospedale Santa Chiara, Trento, Italy). Circulating cardiovascular biomarkers in recurrent atrial fibrillation: data from the GISSI‐Atrial Fibrillation Trial. J Intern Med 2011; 269 : 160–171. Objective. We evaluated the prognostic role of circulating cardiovascular biomarkers in patients with a history of recent atrial fibrillation (AF). Background. Predicting long‐term maintenance of sinus rhythm in patients with AF is difficult. Methods. Plasma concentrations of three specific cardiac markers [high‐sensitivity troponin T (hsTnT), N‐terminal probrain natriuretic peptide (NT‐proBNP) and mid‐regional proatrial natriuretic peptide (MR‐proANP)] and three stable fragments of vasoactive peptides [mid‐regional proadrenomedullin (MR‐proADM), copeptin (CT‐proAVP) and CT‐proendothelin‐1 (CT‐proET‐1)] were measured at baseline and after 6 and 12 months in 382 patients enrolled in the GISSI‐AF study, a prospective randomized trial to determine the effect of valsartan to reduce the recurrence of AF. The association between these markers, clinical characteristics and recurrence of AF was tested by univariate and multivariate Cox models. Results. Mean patient age was 68 ± 9 years (37.2% females). A total of 84.8% of patients had a history of hypertension. In total, 59.7% qualified for history of AF because of successful cardioversion, 11.8% because of two or more episodes of AF in the 6 months preceding randomization and 28.5% because of both. Patients in AF at 6 or 12 months (203 (53.1%) with first recurrence) had significantly higher concentrations of most biomarkers. Despite low baseline levels, higher concentrations of hsTnT {adjusted hazard ratio (HR) [95% confidence intervals (CIs) for 1 SD increment] (1.15 [1.04–1.28], P = 0.007), MR‐proANP (1.15 [1.01–1.30], P = 0.04), NT‐proBNP (1.24 [1.11–1.39], P = 0.0001) and CT‐proET‐1 (1.16 [1.01–1.33], P = 0.03) independently predicted higher risk of a first recurrence of AF. Changes over time of MR‐proANP tended to predict subsequent recurrence (adjusted HR [95%CI]) (1.53 [0.98–2.37], P = 0.06). Conclusion. Circulating markers of cardiomyocyte injury/strain and endothelin are related to recurrence of AF in patients in sinus rhythm with a history of recent AF.     

Searching for Preclinical Models of Acute Decompensated Heart Failure: a Concise Narrative Overview and a Novel Swine Model

Cardiovascular Drugs and Therapy - Available animal models of acute heart failure (AHF) and their limitations are discussed herein. A novel and preclinically relevant porcine model of decompensated...     

Clinical, neurohormonal, and inflammatory markers and overall prognostic role of chronic obstructive pulmonary disease in patients with heart failure: data from the Val-HeFT heart failure trial

BackgroundChronic obstructive pulmonary disease (COPD) and heart failure are major causes of death and disability. Because little information is available about the population of patients with both syndromes, we assessed the characteristics and the independent contribution of COPD to outcomes in patients with stable chronic heart failure.MethodsThe clinical, neurohormonal, and echocardiographic characteristics of the 5010 patients enrolled in the Valsartan Heart Failure Trial were compared in patients with or without COPD. The prognostic value of COPD was tested by multivariate Cox proportional hazard models.ResultsPatients with COPD were older, more symptomatic, and less likely to be receiving beta-blocker therapy, and had a higher mortality (27.4% vs. 18.4%, P < .0001). Echocardiographic parameters were not different, and brain natriuretic peptide was only minimally increased. Norepinephrine, inflammatory markers, cardiac troponin T, and creatinine values were significantly higher. After adjustment, COPD no longer predicted all-cause mortality but remained predictive of noncardiovascular mortality (hazard ratio 2.50; 95% confidence interval: 1.58–3.96; P < .0001) and hospitalizations, especially noncardiovascular (hazard ratio 1.71; 95% confidence interval; 1.43–2.06; P < .0001).ConclusionsPatients with COPD are more symptomatic and have worse outcomes that are not explained by poorer left ventricular function. After adjustment for demographic, clinical, biohumoral, and treatment variables, COPD is a weak predictor of all-cause mortality but a strong predictor of noncardiovascular events. Awareness and optimized treatment of heart failure and COPD may reduce the clinical burden of these patients.     

Heart failure trials on pharmacological therapy in 2015: lessons learned and future outlook

Much progress in the medical therapy of chronic heart failure (HF) has been made in the last decades. The last was the introduction of a new treatment strategy based on the combination of the neprilysin inhibitor sacubitril and the angiotensin receptor blocker (ARB) valsartan into the pharmacological armamentarium, as reported in the PARADIGM-HF trial and its ancillary analyses. On the other hand, in the acute setting only scant progress in pharmacological treatments has been achieved, and most published data are based on observational studies or expert opinion. This review critically presents and discusses the most intriguing evidence from clinical trials in HF published in 2015. In particular, we focused on chronic HF with reduced ejection fraction and its comorbidities, while worsening HF or acute decompensated HF were more synthetically treated.