Prevalence and prognostic significance of heart failure with preserved ejection fraction in systemic sclerosis.

Aim: Heart failure with preserved ejection fraction (HFpEF) is a clinically relevant complication of systemic sclerosis (SSc). We aimed to examine the prevalence, correlates and prognostic significance of HFpEF in an SSc population. Materials & methods: HFpEF was defined by the presence of exertional dyspnoea, abnormal cardiac structure (left ventricular hypertrophy or left atrial enlargement) and NT-proBN (>125 pg/ml). Results: Of the 155 studied patients, 27% had HFpEF criteria. These patients were older, had more cardiovascular risk factors, and were more likely to have atrial fibrillation or interstitial lung disease. Conclusion: Over a median follow-up of 9 years, SSc patients with HFpEF had a 3.4-fold increased risk of dying (HR: 3.37, 95% CI: 1.21-9.31), although this association has lost statistical significance after adjusting for age. On the contrary, NT-proBNP was an independent predictor of a worse prognosis.

Lay abstract Heart failure with preserved ejection fraction (HFpEF) is the most common heart failure type worldwide and can be a complication of the rare disease of systemic sclerosis (SSc). In this study, we examined the proportion of SSc patients who presented the diagnostic criteria of HFpEF. Of the 155 studied patients with SSc, one out of four had those HFpEF criteria. These patients were older, had more cardiovascular risk factors, and were more likely to have arrhythmias or lung disease. Over 9 years, SSc patients with HFpEF had a 3.4-fold increased risk of dying, although this association was lost after adjusting for age. NT-proBNP, a heart failure plasma biomarker, was an independent predictor of worse prognosis.

External validation of different clinical and echocardiographic scores to distinguish post- from precapillary pulmonary hypertension.

BACKGROUND: Even though right heart catheterization (RHC) is the gold-standard method to characterise Pulmonary Hypertension (PH), it cannot be performed in all the patients with suspected PH. Clinical and echocardiographic scores have been developed to differentiate PH secondary to heart failure with preserved ejection fraction (PH-HFpEF) from pre-capillary PH. We aimed to compare the performance of non-invasive parameters in a population with suspected PH. METHODS: We retrospectively included consecutive patients who underwent RHC for suspected PH. Patients with a non-invasive evaluation clearly suggestive of left heart disease were excluded. We assessed the performance of non-invasive pulmonary vascular resistance (PVR), echocardiographic pulmonary to left atrial ratio (ePLAR), and Opotowsky, Richter, Berthelot, and D'Alto scores using the area under curve (AUC) of the receiver operating characteristic curves. RESULTS: Of the 142 included patients, 61 patients had pre-capillary PH, 49 had PH-HFpEF, and 32 patients did not meet invasive criteria for PH. We were able to perform the aforementioned scores in 71-100% of our patients. Using the original cut-offs, Opotowsky was the score that best predicted precapillary PH (96% sensitivity, 41% specificity, AUC .69), followed by D'Alto (98% sensitivity, 22% specificity, AUC .60) and Berthelot (32% sensitivity, 90% specificity, AUC .60). Richter score did not discriminate between phenotypes (AUC .50). Using optimised cut-offs, a Berthelot score < 9 predicted precapillary PH with 73% sensitivity and 74% specificity (AUC .73). Single echocardiographic parameters as non-invasive PVR (85% sensitivity, 59% specificity, AUC .72) and ePLAR (73% sensitivity, 76% specificity, AUC .75) showed better prediction performance than the composite studied scores. CONCLUSION: Combined clinical and echocardiographic characteristics can be used to predict pre-capillary PH with moderate performance. The application of these non-invasive parameters in clinical practice can help refine referral to RHC in a population with clinically suspected PH.

An update of the molecular mechanisms underlying doxorubicin plus trastuzumab induced cardiotoxicity.

Cardiotoxicity is a major side effect of the chemotherapeutic drug doxorubicin (Dox), which is further exacerbated when it is combined with trastuzumab, a standard care approach for Human Epidermal growth factor Receptor-type 2 (HER2) positive cancer patients. However, the molecular mechanisms of the underlying cardiotoxicity of this combination are still mostly elusive. Increased oxidative stress, impaired energetic substrate uses and topoisomerase IIB inhibition are among the biological processes proposed to explain Dox-induced cardiomyocyte dysfunction. Since cardiomyocytes express HER2, trastuzumab can also damage these cells by interfering with neuroregulin-1 signaling and mitogen-activated protein kinase (MAPK), phosphoinositide 3-kinase (PI3K)/Akt and focal adhesion kinase (FAK)-dependent pathways. Nevertheless, Dox and trastuzumab target other cardiac cell types, such as endothelial cells, fibroblasts, cardiac progenitor cells and leukocytes, which can contribute to the clinical cardiotoxicity observed. This review aims to summarize the current knowledge on the cardiac signaling pathways modulated by these two antineoplastic drugs highly used in the management of breast cancer, not only focusing on cardiomyocytes but also to broaden the knowledge of the potential impact on other cells found in the heart.

Optimising cardiovascular care of patients with multiple myeloma.

Multiple myeloma (MM) is the third most common haematological malignancy, with increasing prevalence over recent years. Advances in therapy have improved survival, changing the clinical course of MM into a chronic condition and meaning that management of comorbidities is fundamental to improve clinical outcomes. Cardiovascular (CV) events affect up to 7.5% of individuals with MM, due to a combination of patient, disease and treatment-related factors and adversely impact survival. MM typically affects older people, many with pre-existing CV risk factors or established CV disease, and the disease itself can cause renal impairment, anaemia and hyperviscosity, which exacerabate these further. Up to 15% of patients with MM develop systemic amyloidosis, with prognosis determined by the extent of cardiac involvement. Management of MM generally involves administration of multiple treatment lines over several years as disease progresses, with many drug classes associated with adverse CV effects including high rates of venous and arterial thrombosis alongside heart failure. Recommendations for holistic management of patients with MM now include routine baseline risk stratification including ECG and echocardiography and administration of thromboprophylaxis drugs for patients treated with immunomodulatory drugs. Close surveillance of high-risk patients with collaboration between haematology and cardiology is required, with prompt investigation in the event of CV symptoms, in order to identify and treat complications early. Decisions regarding discontinuation of cardiotoxic therapies should be made in a multidisciplinary setting, taking into account the severity of the complication, prognosis, expected benefits and the availability of effective alternatives.

Pre-infarction angina is associated with improved prognosis in diabetic patients with ST-elevation myocardial infarction - data from a contemporary cohort.

BACKGROUND: Pre-infarction angina (PIA) is associated with improved prognosis in patients with ST-elevation myocardial infarction (STEMI). Some studies suggest that diabetes may blunt the effect of ischaemic preconditioning. We sought to study the impact of PIA in diabetic patients with STEMI. METHODS: Consecutive patients with STEMI who underwent primary angioplasty were included. PIA was defined as ≥1 episode of chest pain during the week preceding STEMI diagnosis. Incident major adverse cardiovascular events (MACE) were defined as the first occurrence of all-cause death, stroke or acute myocardial infarction. RESULTS: Of the 1143 included patients, 25% were diabetic and 32% had a history of PIA. Diabetic patients with PIA had smaller infarct sizes as estimated by peak creatine kinase (CK) [1144 (500-2212) vs. 1715 (908-3309) U/L, P = 0.003] and peak troponin [3.30 (1.90-6.58) vs. 4.88 (2.50-9.58) ng/ml, P = 0.002], compared to diabetics without PIA. They also had a lower likelihood of evolving with moderate to severe reduced left ventricle ejection fraction (LVEF) (25.6%, n = 22 vs. 46.6%, n = 82, P = 0.001). In non-diabetic patients, PIA was associated with reduced peak CK [1549 (909-2909) vs. 1793 (996-3078), P = 0.0497], but not troponin (3.74 [2.23-7.11] vs. 4.56 [2.44-7.77] ng/ml, P = 0.19), and was not associated with reduced LVEF (32.0%, n = 85 vs. 37.4%, n = 207, P = 0.13). Both diabetic and non-diabetic patients with PIA had a lower likelihood of evolving with a Killip class III/VI (non-diabetic patients: 5.6% vs. 14.1%, P = 0.002; diabetic patients: 12.8% vs. 24.6%, P = 0.049). Over a median follow-up of 18.0 (12.1-25.5) months, PIA was associated with a significant reduction in the incidence of MACE [hazard ratio 0.52, 95% confidence interval (CI) 0.37-0.74, P < 0.001], irrespective of diabetes status. CONCLUSION: PIA is an independent predictor of favourable outcomes in the setting of STEMI for both diabetic and non-diabetic patients.

Cardiovascular rehabilitation in patients aged 70-year-old or older: benefits on functional capacity, physical activity and metabolic profile in younger vs. older patients.

BACKGROUND: The benefits of exercise-based cardiac rehabilitation (EBCR) programs in post-acute myocardial infarction (AMI) patients have been demonstrated. Our aim was to assess the impact of EBCR in ≥ 70-years-old vs. younger post-AMI patients. METHODS: We retrospectively evaluated patients who underwent a supervised EBCR protocol, twice a week during 6-12 weeks. We evaluated changes in several outcomes based on pre- and post-CRP assessments. RESULTS: Of a total of 1607 patients, 333 (21%) were ≥ 70-years-old. After the EBCR, an overall improvement on functional capacity, daily physical activity, lipid profile, body mass index, glycated hemoglobin (HbA1c), N-terminal pro-brain natriuretic peptide (NT-pro-BNP) and C-reactive protein was observed in both younger and older patients (P < 0.05). Older patients showed a smaller benefit on the increment of daily physical activity and lipid profile improvement, but a larger reduction in NT-pro-BNP. In the multivariate analysis, only improvements on daily physical activity and HbA1c were dependent on age. CONCLUSION: As their younger counterparts, older patients, significantly improved functional capacity, metabolic parameters and level of daily physical activity after EBCR.

Predictors of In-Hospital Mortality after Recovered Out-of-Hospital Cardiac Arrest in Patients with Proven Significant Coronary Artery Disease: A Retrospective Study.

INTRODUCTION: Recovered Out-of-Hospital Cardiac Arrest (rOHCA) population is heterogenous. Few studies focused on outcomes in the rOHCA subgroup with proven significant coronary artery disease (SigCAD). We aimed to characterize this subgroup and study the determinants of in-hospital mortality. METHODS: Retrospective study of consecutive rOHCA patients submitted to coronary angiography. Only patients with SigCAD were included. RESULTS: 60 patients were studied, 85% were male, mean age was 62.6 ± 12.1 years. In-hospital mortality rate was 43.3%. Patients with diabetes and history of stroke were less likely to survive. Significant univariate predictors of in-hospital mortality were further analysed separately, according to whether they were present at hospital admission or developed during hospital evolution. At hospital admission, initial non-shockable rhythm, low-flow time>12min, pH<7.25mmol/L and lactates >4.75mmol/L were the most relevant predictors and therefore included in a score tested by Kaplan-Meyer. Patients who had 0/4 criteria had 100% chance of survival till hospital discharge, 1/4 had 77%, 2/4 had 50%, 3/4 had 25%. Patients with all 4 criteria had 0% survival. During in-hospital evolution, a pH<7.35 at 24h, lactates>2mmol/L at 24h, anoxic brain injury and persistent hemodynamic instability proved significant. Patients who had 0/4 of these in-hospital criteria had 100% chance of survival till hospital discharge, 1/4 had 94%, 2/4 had 47%, 3/4 had 25%. Patients with all 4 criteria had 0% survival. Contrarily, CAD severity and ventricular dysfunction didn't significantly correlate to the outcome. CONCLUSION: Classic prehospital variables retain their value in predicting mortality in the specific group of OHCA with SigCAD. In-hospital evolution variables proved to add value in mortality prediction. Combining these simple variables in risk scores might help refining prognostic prediction in these patients's subset.

Echocardiographic Assessment of Right Ventriculo-arterial Coupling: Clinical Correlates and Prognostic Impact in Heart Failure Patients Undergoing Cardiac Resynchronization Therapy.

BACKGROUND: Right ventriculo-arterial coupling (RV-PA) can be estimated by echocardiography using the ratio between tricuspid annular plane systolic excursion (TAPSE) and pulmonary artery systolic pressure (PASP) and it has prognostic value in the general heart failure (HF) population. We aimed to study the clinical correlates and prognostic value of RV-PA in HF patients undergoing cardiac resynchronization therapy (CRT). METHODS: We retrospectively studied 70 HF patients undergoing CRT implantation. RESULTS: RV-PA coupling was estimated by TAPSE/PASP ratio using baseline echocardiography. Non-response to CRT was defined as improvement of left ventricular ejection fraction < 5% in a follow-up echo 6-12 months after CRT. Those with lower TAPSE/PASP ratios (worse RV-PA coupling) had higher NT-proBNP concentrations and increased E/e' ratio. TAPSE/PASP ratio and PASP, but not TAPSE, predicted nonresponse to CRT with TAPSE/PASP ratio showing the best discriminative ability with a sensitivity of 76% and specificity of 71%. Among these parameters, PASP independently predicted all-cause mortality. CONCLUSIONS: RV-PA coupling estimated by TAPSE/PASP ratio was associated with established prognostic markers in HF. It numerically outperformed PASP and TAPSE in predicting the response to CRT. Our data suggest that this simple and widely available echocardiographic parameter conveys significant pathophysiological and prognostic meaning in HF patients undergoing CRT.

Polineuropatía amiloidótica familiar Val30Met, insuficiencia cardiaca y ascitis quilosa: una cómbinacion inesperada / Val30Met familial amyloid polyneuropathy, heart failure, and chylous ascites: an unexpected combination

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Influence of epicardial and visceral fat on left ventricular diastolic and systolic functions in patients after myocardial infarction.

Obesity has been associated with subclinical left ventricular (LV) diastolic dysfunction and increased risk of heart failure. Few data are available on the relative contribution of adiposity distribution and changes in myocardial structure and function. We evaluated the influence of visceral versus subcutaneous abdominal adipose tissue and epicardial fat on LV diastolic function after acute myocardial infarction. One month after acute myocardial infarction, 225 consecutive patients were prospectively enrolled and underwent anthropometric evaluation, bioimpedance analysis, detailed echocardiography, and multidetector 64-slice computed tomography scan for quantification of epicardial fat volume (EFV) and of total, subcutaneous and visceral abdominal fat areas. We found a significant association between LV diastolic dysfunction parameters and body mass index, fat-mass percentage, and waist-to-height ratio. E' velocity and E/E' ratio were correlated with total and visceral abdominal fat (r = -0.27, p <0.001 and r = 0.21, p <0.01, respectively), but not with subcutaneous fat. After multivariate analysis, increasing EFV was associated with decreased E' velocity (adjusted ß -0.11, 95% confidence interval -0.19 to -0.03; p <0.01) and increased E/E' ratio (adjusted ß 0.19, 95% confidence interval 0.07 to 0.31, p <0.01). Patients with diastolic dysfunction showed higher EFV (116.7 ± 67.9 ml vs 93.0 ± 52.3 ml, p = 0.01), and there was a progressive increase in EFV according to diastolic dysfunction grades (p = 0.001). None of the adiposity parameters correlated with ejection fraction or S' velocities. In conclusion, in patients after myocardial infarction, impaired LV diastolic function was associated with increased adiposity, especially with visceral and central fat parameters. Increasing EFV was independently associated with worse LV diastolic function.