Clinical Evidence Of Heart Failure Research Articles

Genotype-phenotype correlation of transthyretin cardiomyopathy in patients with stage C/D heart failure: atrial and myocardial mechanics and fibrosis

Abstract Objectives We sought to investigate: (1) the relationship between transthyretin (TTR) pathogenic variants and their corresponding echocardiographic atrial and ventricular strains in patients with TTR cardiomyopathy (TTR-CM) and clinical evidence of heart failure (HF), and (2) the relationship between TTR pathogenic variants and atrial fibrosis assessed by cardiac MRI. Methods and results Fifty Asian patients with biopsy or scintigraphy proven TTR-CM and stage C or D (C/D) HF were identified from an advanced HF clinic in a tertiary-care university hospital. Genetic testing for the pathogenic variants in the TTR genes associated with hereditary TTR-CM (hTTR-CM) was available in 22 patients (67 ±13 years; 77% were male). Of these, 3 different mutations were identified. The most prevalent pathogenic variant was Ala97Ser (67%) followed by Val30Met (27%), and Gly67Glu (6%). Wild-type TTR-CM was diagnosed in 32% of the cohort. Strain analysis was performed using the TomTec Arena 2D-cardiac performance analysis (CPA) software. Atrial and left ventricular (LV) late gadolinium enhancement (LGE) was quantified using a 9-segment and a 17-segment model, respectively. Patients with hTTR-CM had less impaired longitudinal strain (LS) (more negative strain values) than those with wild-type TTR-CM in the regional basal right ventricular free wall (RV-FW) (-21 ± -8.3 % vs.-12.6 ± -8.1%, p = 0.048) and LV basal inferoseptum (-7.3 ± -4.1 % vs.-3.1 ± -3.0 %, p = 0.045). In univariate analysis, more negative LS values in the basal LV inferoseptum and basal RV-FW were significant predictors of hTTR-CM (OR 5.1 and 2.3; p <0.05, respectively). However, MRI findings revealed similar regional LGE extent involving basal inferolateral segments between hTTR-CM and wild-type TTR-CM (38.3 ± 7.9 vs. 52.5 ± 34.5%, p =0.314). Left atrial (LA) and right atrial (RA) LGE was present in 90% and 81% of patients, respectively. Patients with hTTR-CM had reduced RA LGE when compared to those with wild-type TTR-CM (41% vs 67%, p =0.039). Conclusions In patients with TTR-CM and stage C/D HF, a reduced RA LGE extent and/or more preserved myocardial deformation in specific regions of basal LV and RV segments (basal LV inferoseptum and basal RV free wall) assessed by 2-D speckle tracking echocardiography were significantly more prevalent in patients with hTTR-CM than in wild-type TTR-CM. These echocardiographic and/or MRI findings may facilitate genotype testing in patients with TTR-CM, particularly in resource-limited settings. Further validation of these novel findings in patients with TTR-CM with HF is needed.

P352 EXPLORATORY ANALYSES FROM APOLLO–B, A PHASE 3 STUDY OF PATISIRAN IN PATIENTS WITH ATTR AMYLOIDOSIS WITH CARDIOMYOPATHY

Abstract Introduction Transthyretin–mediated (ATTR) amyloidosis is a progressive and fatal disease. Patients with hereditary or wild–type ATTR amyloidosis frequently develop cardiomyopathy (CM). Patisiran, an IV RNAi therapeutic that inhibits synthesis of wt and variant TTR, is approved for the treatment of hATTR amyloidosis with polyneuropathy. Methods In APOLLO–B, patients were 18–85 yrs old with evidence of cardiac amyloidosis by echocardiography, ATTR amyloid deposition on tissue biopsy or fulfilling nonbiopsy diagnostic criteria for ATTR amyloidosis with CM, and had prior hospitalization for heart failure (HF) due to ATTR amyloidosis or clinical evidence of HF. Patients were randomized 1:1 to patisiran IV 0.3 mg/kg or placebo Q3W for 12 months. The primary endpoint was change from baseline in 6–MWT at Month 12 (M12) with patisiran vs placebo. Exploratory parameters at M12 included changes in cardiac biomarkers, echocardiography and Tc scintigraphy. Results APOLLO–B enrolled 360 patients (patisiran, n=181; placebo, n=179): median age, 76.0 yrs; male, 89%; wtATTR, 80%; on tafamidis at baseline, 25%. Patisiran showed a significant benefit compared with placebo in 6–MWT (median [95% CI] change from baseline: patisiran, –8.15 [–16.42, 1.50]; placebo, –21.35 [–34.05, –7.52]; HL estimate of median difference: 14.69 [0.69, 28.69]; p=0.0162). Patisiran demonstrated favorable trends in change from baseline of NT–proBNP (mean fold change ratio [95% CI]: 0.80 [0.73, 0.89]; p=1.825×10–5) and troponin I (mean fold change ratio [95% CI]: 0.87 [0.80, 0.95]; p=0.0011) at M12 vs placebo. Patisiran also demonstrated a trend towards benefit in change from baseline of most evaluated echocardiographic parameters at M12 vs placebo. Patisiran–treated patients evaluable for scintigraphy (n=37) experienced a reduction (37.8%) or no change (62.2%) in Perugini grade at M12 compared with baseline. Among placebo patients (n=28) at M12, none experienced a reduction from baseline in Perugini grade, and 1 (3.6%) increased in grade. Patisiran demonstrated an acceptable safety profile; AEs were mostly mild or moderate in severity, and there were no cardiac safety concerns. Conclusions Exploratory analyses after 12 months provide further evidence for the potential benefit of patisiran treatment on cardiac biomarkers and manifestations of cardiac amyloid involvement in patients with ATTR amyloidosis. The long–term impact of patisiran will be assessed in the ongoing APOLLO–B open–label extension.

P78 AN ANTEGRADE RECANALIZATION OF LEFT ANTERIOR DESCENDING CHRONIC TOTAL OCCLUSION WITH ORBITAL ATHERECTOMY IN PATIENT WITH SEVER LEFT VENTRICULAR DISFUNCTION

Abstract We share the case of a 71–year old man, affected by hypertension, presented in Emergency Room (ER) with chest pain. No clinical evidence of heart failure. EKG showed fast atrial fibrillation with QS complex and ST elevation in precordial leads. Echocardiogram confirmed sept and apex akinesia. Troponin I peak was 72pg/ml. In ER electrical cardioversion was efficacy performed. He was referred for invasive coronary angiography, that showed a left anterior descending (LAD) chronic total occlusion (CTO), with Rentrop grade 2 collaterals providing retrograde flow from the right coronary artery (RCA), a severe stenosis of ramus intermedius (RI) and a moderate stenosis of circumflex. A stress–echocardiogram demonstrated vitality of medio–basal anterior wall. Subsequent, recanalization procedure of LAD CTO was planned. J–CTO score was 1 (tapered calcific, lesion, <20mm). double radial access and ante grade approach was chosen. An EBU3.5 guiding catheter was engaged in the left coronary artery, and 8000 units of heparin administered. The iFR of Cx was 0.99, indicative of non significant myocardial ischemia. During hemodynamic evaluation of RI, a ventricular fibrillation occurred, treated by DC–SHOCK and PCI with stenting with no polymer, eluted with Biolimus A9 (3.0x24mm) with good result. The occlusion was crossed via an antegrade approach with an Asahi Gaia II wire and with microcatheter support. Gaia II was changed in favor of Asai Sion blu, and the IVUS catheter was enable of cross the lesion. Efficacy orbital atherectomy with Diamondback 260 was performed (5 ante and retro grade run at 80Krpm and a retro grade run at 120 Krpm. Ivus was able to cross the lesion. Efficacy pre–dilatation with semi and non compliant balloon (2.5–3.5mm) was performed and then stented with a 3.0 × 36 mm Bioloimu A9–eluting stent. Finally, IVUS confirmed correct stent expansion, achieving an excellent angiographic result. Patient was discharged with triple anti–thrombotic therapy, with indication to “life jacket” till the assessment at 1 month.

P63 OPTICAL COHERENCE TOMOGRAPHY–ANGIO CO–REGISTRATION (OCT–ACR) OF LEFT ANTERIOR DESCENDING IN PATIENT WITH ONGOING ANIGNA

Abstract We share the case of a 50–year old man, with no cardiovascular risk factor, presented in ER with ongoing angina and positive exercise stress testing. No clinical evidence of heart failure. EKG and echocardiogram was negative. He was referred for invasive coronary angiography, that showed severe stenosis of mid–LAD and moderate ostial LAD stenosis. Subsequent Optical Coherence Tomography–Angio Co–Registration (OCT–ACR) of Left Anterior Descending was performed. An EBU3.5 guiding catheter was engaged in the left coronary artery, and 8000 units of heparin administered. After a pre–dilatation with a semi–compliant balloon of mid LAD, a plaque rupture with thrombus was documented at mid–LAD and a fibro–lipidic plaque with a severe flow limitation (MLA<4mm2) at the ostium, with no involvement of left main (Fig. 1b). Pre–dilatation with SC and NC balloon (2.5–3.5mm) was performed and then stented with a 4.0 × 26 mm DES. Finally, OCT confirmed correct stent expansion, achieving an excellent angiographic result, without carina shifting and compromise of the circ. Patient was discharged, asymptomatic. OCT–ACR guided PCI, taking advantage of its high spatial resolution, permits to plain better the PCI, establish correct stent size, evaluate early complications especially if left main or bifurcation are involved and thanks to co–registration also measurement of long axis of the vessel are facilitated.

Essential Therapy for Heart Failure with Preserved Ejection Fraction in 2022

Heart failure with preserved ejection fraction (HFpEF) is a syndrome in which there is clinical evidence of heart failure (HF), left ventricle ejection fraction (LVEF) ≥50%, and evidence of diastolic dysfunction and/or structural cardiac changes. The pathophysiology of HF with preserved LVEF is related to the primary morbidities responsible for cardiac and vascular aggression via a chronic proinflammatory state involving the endothelium. Currently, the foundation of management of HFpEF rests on 5 pillars: control of circulatory congestion, management of [...]

A pilot study on right ventricular longitudinal strain as a predictor of outcome in COVID-19 patients with evidence of cardiac involvement.

The aim of this investigation was to evaluate echocardiographic parameters of cardiac function and in particular right ventricular (RV) function as a predictor of mortality in patients with coronavirus disease-2019 (COVID-19) pneumonia. This prospective observational study included 35 patients admitted to a UK district general hospital with COVID-19 and evidence of cardiac involvement, that is, raised Troponin I levels or clinical evidence of heart failure during the first wave of the COVID-19 pandemic (March-May 2020). All patients underwent echocardiography including speckle tracking for right ventricular longitudinal strain (RVLS) providing image quality was sufficient (30 out of 35 patients). Upon comparison of patients who survived COVID-19 with non-survivors, survivors had significantly smaller RVs (basal RV diameter 38.2 vs 43.5mm P=.0295) with significantly better RV function (Tricuspid annular plane systolic excursion (TAPSE): 17.5 vs 15.3mm P=.049; average RVLS: 24.3% vs 15.6%; P=.0018). Tricuspid regurgitation (TR) maximal velocity was higher in survivors (2.75m/s vs 2.11m/s; P=.0045) indicating that pressure overload was not the predominant driver of this effect and there was no significant difference in left ventricular (LV) ejection fraction. Kaplan-Meier and log-rank analysis of patients split into groups according to average RVLS above or below 20% revealed significantly increased 30-day mortality in patients with average RVLS under 20% (HR: 3.189; 95% CI: 1.297-12.91; P=.0195). This study confirms that RVLS is a potent and independent predictor of outcome in COVID-19 patients with evidence of cardiac involvement.

Flow mapping of Intraventricular velocity behaviour along the early diastolic filling streamline in patients with atrial fibrillation: implication for HFpEF

Abstract Aims Intraventricular velocity distribution reflects left ventricular (LV) diastolic function and can be measured non-invasively by flow mapping technologies. We sought to compare intraventricular velocity gradient during early diastole – obtained by vector flow mapping (VFM) technology – in consecutive patients with normal ejection fraction (EF >55%) and atrial fibrillation (AF) with and without clinical evidence of heart failure (HFpEF), and controls in sinus rhythm. We hypothesised that the VFM-derived Intraventricular Velocity Gradient over e' ratio (GrIV/e') would discriminate between the groups beyond conventional echocardiographic markers of elevated LV filling pressure. Methods and results Two-dimensional streamline fields were obtained using VFM technology in 120 subjects, i) 60 in sinus rhythm with normal systolic and diastolic function, ii) 29 out-patients with AF and no signs or symptoms of heart failure, and iii) 31 patients in AF hospitalized with signs of HFpEF. We compared the intraventricular gradient along the early diastolic streamline between groups, and correlated it with conventional echocardiographic parameters. GrIV/e' was the lowest in control group, followed by AF without HFpEF and the highest in AF HFpEF groups (GrIV/e' = 0.5±0.2, vs 0.9±0.4 vs. 2.0±1.2, p<0.001, Figure, left). Conversely, LV filling pressure as determined by E/e', while lowest in the control group, failed to discriminate between patients with AF with and without (E/e' = 10.0±3.7 vs. 9.5±2.1, p=0.456, Figure, right). Conclusion The novel VFM parameter – reflecting early-diastole intraventricular dynamics – may discriminate between patients with AF with and without HFpEF beyond conventional echocardiography. While further studies are need to validate its clinical impact, GrIV/e' has the potential to become a novel parameter for diastolic function assessment in this population. VFM vs. Conventional echo parameter Funding Acknowledgement Type of funding source: None

SAT-503 Levothyroxine Absorption Testing in Three Patients with Severe Hypothyroidism on Adequate Replacement

Background: Levothyroxine (L-T4) absorption is a concern in patients who report appropriate self-administration but remain clinically and biochemically hypothyroid. However, there are no established guidelines for L-T4 absorption testing. Clinical Cases: Two women (A and B) with a history of Graves’ disease and radioactive iodine ablation (RAI) on weight-based L-T4 replacement presented to the hospital with severe fatigue and bilateral leg swelling. A third woman (C) with a history of papillary thyroid carcinoma, total thyroidectomy and RAI, on suppressive doses of L-T4 presented to the clinic with fatigue, constipation and weight gain. All patients reported compliance with taking L-T4 with appropriate technique. They had no known medical problems contributing to a malabsorptive state, and were not taking any medications known to interfere with L-T4 absorption.Initial testing of thyroid function revealed TSH (0.57-3.5 μIU/mL)/Free T4 (0.61-1.18 ng/dL) levels of 10.12/0.249, 45.95/<0.2 and 142/<0.2 in patients A, B and C respectively. Patients A and B tested negative for Helicobacter pylori infection, celiac disease and lactose intolerance. Patient C had been successfully treated for H. pylori infection in the past. Celiac testing was negative, but the patient tested positive for anti-parietal cell antibodies and vitamin B12 deficiency. She was referred to Hematology & GI specialists. None of the patients had clinical evidence of heart failure and had normal echocardiograms.In order to evaluate for poor absorption, all patients underwent L-T4 absorption testing. Based on published data, baseline TSH and Free T4 levels were obtained followed by administration of 1000 mcg of L-T4. Next, free T4 levels were obtained at 2 hours for all patients and at 4, 8 and 24 hours for patient A & B. Patients A and B underwent testing in the inpatient setting, while Patient C was tested in the outpatient clinic.In all cases, a > 50% rise in free T4 levels was observed at 2 hours, suggesting non-adherence or “pseudo-malabsorption”. Patients were counseled extensively regarding proper technique and compliance with L-T4. Patients A and B demonstrated rapid clinical improvement in the hospital, and Patient C reported to her next clinic visit with clinical and biochemical improvement. Conclusions: Though guidelines have not been established for L-T4 absorption testing, case reports exist exhibiting the safety and efficacy of L-T4 absorption challenge with a weekly weight-based dose or 1000 mcg of LT4. Our case series show the success of the latter with meaningful results in as little as 2 hours. Case C demonstrates that this test can be done safely and cost-effectively as an outpatient. Standardization of L-T4 absorption test will be of great utility in the management of this common problem encountered by endocrinologists.

The "Heart Valve Clinic" Pathway for the Management of Frail Patients With Valvular Heart Disease: From "One for All" to "All for One".

Valvular heart disease (VHD) is frequently diagnosed in old patients with clinical evidence of heart failure. This elderly population typically presents a high prevalence of frailty and comorbidities, which are associated with increased operative risk for surgical and percutaneous procedures. Recently, the Euro Heart Survey reported a clear gap between treatment guidelines and their application in the "real world". A more realistic approach to the treatment of older VHD patients treatment, mostly if associated with heart failure, is advocated. A multidisciplinary approach, as obtained with the Heart Valve Clinic methodology (intended to put the patient in the "center" of the scene and the specialists "around him"), has been applied in a group of 79 patients, aged >70 years, with symptomatic VHD, divided in 2 groups according to their frailty status (58 robust and 21 frail). No in-hospital mortality and no difference in late mortality and complications were observed. Infections were more frequent (14.3 vs. 1.7 %; P = 0.02) in frail patients. In patients with postoperative complications, serum levels of interleukin 6 (67.6 vs. 49.6; P = 0.01) and of CAF (C-terminal agrin fragment) as sarcopenia marker (67.9 vs. 62.0; P = 0.04) were higher than that in uncomplicated patients. This study was designed to determine the outcomes of the multidimensional geriatric assessment in the management of older patients with heart failure eligible for heart valve surgery. Geriatric assessment and measurement of inflammatory and sarcopenia markers may represent valid tools for a more realistic evaluation of elderly patients with VHD.

Association Between Plasma Brain Natriuretic Peptide and Overall Survival in Patients With Advanced Cancer: Preliminary Findings

ContextAtrial and brain natriuretic peptides (ANP and BNP) are established diagnostic and prognostic markers in heart failure, but their utility in patients with advanced cancer is unclear. ObjectivesOur objective was to examine the association between plasma natriuretic peptides and survival in patients with advanced cancer without clinical evidence of heart failure. MethodsThis exploratory analysis of a multicenter, randomized clinical trial of cancer patients receiving hospice care assessed the association between elevated plasma ANP, BNP, or Pro-BNP (cutoffs of >77, 100, and 900 pg/mL, respectively) and overall survival. Time-to-event analyses, including multivariate Cox regression, were conducted. ResultsAmong 97 patients, the mean age was 67.2 years and the overall survival was 16 days (95% CI, 13–23 days). ANP, BNP, and Pro-BNP were elevated in 29 of 36 (81%), nine of 23 (39%), and 32 of 38 (84%) patients, respectively. Elevated ANP, BNP, or Pro-BNP was associated with worse survival (median 14 vs. 21 days; P = 0.02). BNP or Pro-BNP was inversely associated with overall survival (hazard ratio = 2.27; 95% CI, 1.29–3.97) in univariate Cox regression analysis, and remained significant in multivariate Cox regression analysis (hazard ratio = 3.09; 95% CI, 1.40–6.84) after adjusting for treatment group and known prognostic variables such as performance status, albumin, creatinine, delirium, dyspnea, and anorexia. Elevated ANP alone was not significantly associated with survival (P = 0.17). ConclusionOur preliminary findings suggest that BNP or Pro-BNP may be a novel objective prognostic marker in cancer patients without heart failure. Further research is needed to confirm these findings.

Withdrawal of pharmacological treatment for heart failure in patients with recovered dilated cardiomyopathy (TRED-HF): an open-label, pilot, randomised trial

SummaryBackgroundPatients with dilated cardiomyopathy whose symptoms and cardiac function have recovered often ask whether their medications can be stopped. The safety of withdrawing treatment in this situation is unknown.MethodsWe did an open-label, pilot, randomised trial to examine the effect of phased withdrawal of heart failure medications in patients with previous dilated cardiomyopathy who were now asymptomatic, whose left ventricular ejection fraction (LVEF) had improved from less than 40% to 50% or greater, whose left ventricular end-diastolic volume (LVEDV) had normalised, and who had an N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) concentration less than 250 ng/L. Patients were recruited from a network of hospitals in the UK, assessed at one centre (Royal Brompton and Harefield NHS Foundation Trust, London, UK), and randomly assigned (1:1) to phased withdrawal or continuation of treatment. After 6 months, patients in the continued treatment group had treatment withdrawn by the same method. The primary endpoint was a relapse of dilated cardiomyopathy within 6 months, defined by a reduction in LVEF of more than 10% and to less than 50%, an increase in LVEDV by more than 10% and to higher than the normal range, a two-fold rise in NT-pro-BNP concentration and to more than 400 ng/L, or clinical evidence of heart failure, at which point treatments were re-established. The primary analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT02859311.FindingsBetween April 21, 2016, and Aug 22, 2017, 51 patients were enrolled. 25 were randomly assigned to the treatment withdrawal group and 26 to continue treatment. Over the first 6 months, 11 (44%) patients randomly assigned to treatment withdrawal met the primary endpoint of relapse compared with none of those assigned to continue treatment (Kaplan-Meier estimate of event rate 45·7% [95% CI 28·5–67·2]; p=0·0001). After 6 months, 25 (96%) of 26 patients assigned initially to continue treatment attempted its withdrawal. During the following 6 months, nine patients met the primary endpoint of relapse (Kaplan-Meier estimate of event rate 36·0% [95% CI 20·6–57·8]). No deaths were reported in either group and three serious adverse events were reported in the treatment withdrawal group: hospital admissions for non-cardiac chest pain, sepsis, and an elective procedure.InterpretationMany patients deemed to have recovered from dilated cardiomyopathy will relapse following treatment withdrawal. Until robust predictors of relapse are defined, treatment should continue indefinitely.FundingBritish Heart Foundation, Alexander Jansons Foundation, Royal Brompton Hospital and Imperial College London, Imperial College Biomedical Research Centre, Wellcome Trust, and Rosetrees Trust.

Echocardiographic assessment of Left Ventricular Dyssynchrony in Hypertensive Patients with Normal Systolic Function

Background: Normal Left Ventricular systolic function is present in nearly 50% of patients with congestive heart failure, the majority of such patients have systemic hypertension. Recent studies have demonstrated Left Ventricular dyssynchrony among patients with heart failure and normal systolic function. The co-existence between Left Ventricular dyssynchrony and hypertension with normal systolic function (with no clinical evidence of heart failure) is less well understood.&#x0D; Objective:&#x0D; To assess the Left Ventricular dyssynchrony among hypertensive patients with normal systolic function by using Tissue doppler imaging.To find out the associations between the LV dyssynchrony and other global echocardiographic findings like (LA volume index, LVmassindex , LV sephericity and LV filling pressure E/E`)&#x0D; Type of the study: Prospective case- control study&#x0D; Methods: The study conducted in Baghdad Teaching Hospital from 1st of June 2015 to 30th of May 2016 .Study included two groups of people, 40 patients, age_ matched healthy (control) group (group1) and 60 patients with established hypertension (group 2). A Complete 2-D and TDI echocardiography studies with simultaneous ECG were performed for all patients. Examination involved LV septal and posterior wall thicknesses, internal dimensions, left atrial size, ejection fraction and tissue doppler derived waves velocities E', E/E.' Dyssynchrony was determined by measuring T-P max ( the maximal time difference from the onset of QRS to peak systolic velocity on TDI between any opposing LV wall in 3 apical views) .&#x0D; Results: The study included 40 age –matched control people, 27males (67.5%) and 13 females (32.5%) with a male to female ratio was 1.8 :1, ranging from (42.4-58y) with mean age was (50.2 ±7.8y ) (group 1) and 60 hypertensive patients, 38 males (63.3%) and 22 females (36.7%) with a male to female ratio was 1.7 :1, ranging from (48.5- 66.5y) with mean age of (57.5± 9.0 y) (group 2) . Left Ventricular dyssynchrony was identified in 20 of 60 patients (33.3%) .Dyssynchrony had no significant association with age and BSA. But it was significantly associated with LA volume index (r = 0.61, p=0.001), LV mass index(r=0.52 ,p=0.001) , LV sphericity index (r= 0.5, p = 0.003) ) and LV filling pressure(r=0.6 , p value=0.001) . Dyssynchrony had significant negative correlation with ( E`) velocity (r= - 0.7 ,P =0.001) .&#x0D; Conclusion: Left Ventricular dyssynchrony is frequent among hypertensive patients with normal LV systolic function .The Left Ventricular dyssynchrony is significantly related to LA volume, LV mass, LV sphericity and LV filling pressure.

Prevalence of obstructive sleep apnoea in acute coronary syndrome: Routine screening in intensive coronary care units

IntroductionIncreased evidence has shown that, despite the maximum care afforded to patients admitted with acute coronary syndromes (ACS), a residual risk of mortality remains, in which obstructive sleep apnoea (OSA) appears to be a largely undiagnosed factor, particularly in the intensive cardiac care unit (ICCU). The purpose of this study is to determine whether the systematic screening for sleep-disordered breathing (SDB) is feasible and may be recommended. The aims of our study are to determine: (1) The estimated prevalence of OSA in patients admitted to the ICCU for ACS determined by a validated, user-friendly portable screening device; (2) The feasibility of the screening in this context; (3) To assess any negative impact of OSA on the severity of ACS. Patients and methodsThis is an observational study of 101 patients admitted to the ICCU for ACS showing no clinical evidence of heart failure (HF). In the 24–72hours following admission, they underwent an overnight sleep study using a 3-channel portable screening device with automatic analysis. ResultsSixty-two out of the 101 patients proved positive to the screening test, and its feasibility was acceptable. OSA patients tended to have greater peak levels of hs-cTnT (3685±3576ng/L versus 2830±3333ng/L, P=0.08) than the non-OSA group. Compared with the non-OSA group, OSA patients presented more severe ACS, with a greater average GRACE score at admission of 112.2±26.3 (versus 98.4±19.2, P<0.001). In the OSA group, we found a statistically significant inverse correlation between the apnoea-hypopnea index (AHI) and the left ventricular ejection fraction (LVEF) in the linear regression analysis (r=−0.26; P=0.037). ConclusionsA systematic screening of patients in the ICCU is acceptable. OSA is frequently found in the acute phase of ischaemic heart disease and its presence is associated with more severe ACS and a poorer left ventricle systolic function.

The associations among co-morbidity, cardiac geometries and mechanics in hospitalized heart failure with or without preserved ejection fraction

ABSTRACTBackground: The associations among chronic health conditions, ventricular geometric alterations or cardiac contractile mechanics in different phenotypes heart failure (HF) remain largely unexplored. Methods: We studied 438 consecutive hospitalized patients (mean age: 64.9 ± 16.6 years, 52.5% female) with or without clinical evidence of HF. We examined the associations among clinical co-morbidities, LV geometries and systolic mechanics in terms of global myocardial strains. Results: Increasing clinical co-morbidities was associated with greater LV mass, worse longitudinal deformations and higher proportion of admission with HF diagnosis, which was more pronounced in HFpEF (from 6.4% to 40.7%, X2 < 0.001). The independent association between co-morbidity burden and longitudinal functional decay remained unchanged after adjusting for age and sex for all admissions and in HFpEF (Coef: 0.82 & 0.71, SE: 0.13 & 0.21, both p≤0.001). By using co-morbidity scores, the area under receiver operating characteristic curves (AUROC) in identifying HFpEF was 0.71 (95% CI: 0.65 to 0.77), 0.64 (95% CI: 0.58 to 0.71) for HFrEF and 0.72 for both (95% CI: 0.67 to 0.77). Co-morbidity burden superimposed on LV mass index and LV filling pressure (E/E’) further expanded the AUROC significantly in diagnosing both types HF (c-statistics from 0.73 to 0.81, p for ΔAUROC: 0.0012). Conclusion: Chronic health conditions in the admission population were associated with unfavorable cardiac remodeling, impair cardiac contractile mechanics and further added significantly incremental value in HF diagnosis. Our data suggested the potentiality for better cardiac function by controlling baseline co-morbidities in hospitalized HF patients, especially HFpEF.Abbreviations:CAD: coronary artery disease; CKD: chronic kidney disease; DT: deceleration time; eGFR: Estimated glomerular filtration rate; HF: heart failure; IVRT: iso-volumic relaxation time; LV: left ventricular; LVEF: left ventricular ejection fraction; RWT: relative wall thickness; TDI: Tissue Doppler imaging

Elevation of Serum Pro-Brain Natriuretic Peptide in G-CSF Stimulated Hematopoietic Progenitor Cell Donors

Introduction:Healthy donors who are treated with GCSF before peripheral blood hematopoietic progenitor cell (HPC) collection may develop side effects and aberrant laboratory values that have been described with the mobilization regimen. Alternatively, unexpected abnormal laboratory results could reflect occult complications or underlying disease. While many serum chemistry test results are affected by G-CSF, there have been no published reports describing an effect on BNP (pro-brain natriuretic peptide), a serum marker of heart failure. We encountered a donor who developed an elevated BNP after GCSF-stimulated HPC collection, and investigated its possible association with GCSF administration in healthy donors.Case Report:A 41-year old woman was evaluated for matched allogeneic peripheral HPC donation. History and physical exam were unremarkable, and standard laboratory values, EKG and chest X-ray revealed no abnormalities. The donor was mobilized with 10mcg/kg GCSF daily for 5 days. Her only complaint was of headache starting on day 4 that was relieved partially with acetaminophen. No other side effects were recorded.Her pre-apheresis peripheral CD34+ count was 87/mcL. At the start of apheresis HPC collection, the donor reported headache 7/10 in intensity and intolerance to light, unrelieved by acetaminophen but partially relieved with oxycodone. She complained of nausea during collection, but the procedure was otherwise successful and uneventful (15L of whole blood processed). Her headache persisted at the time of discharge, and the donor was counseled and prescribed one additional dose of oxycodone.Five hours after discharge the donor reported “the worst headache of her life”, nausea and difficulty breathing. She was evaluated at the ER, where she had stable vital signs and normal oxygen saturation. Her physical exam was unremarkable. Head CT was negative for intracranial hemorrhage or mass effect. A panel of laboratory analyses revealed leukocytosis, decreased platelets, and increased alkaline phosphatase and liver enzymes, which are documented findings associated with GCSF stimulation and large-volume apheresis. Given the donor’s complaint of dyspnea, serum BNP was measured and found increased to 483pg/mL (normal <124pg/mL). The donor had a normal pulmonary examination and no clinical evidence of cardiac insufficiency; a chest X-ray and an echocardiogram were also within normal limits. Her symptoms resolved with IV hydromorphone and she was discharged in stable condition. A follow-up serum BNP 4 weeks after donation was within normal range (105pg/mL).Investigation:A preliminary study evaluated 11 additional HPC donors who were stimulated with 10mcg/kg GSCF for 5 days (Table 1). Nine of twelve (75%) donors were male, and seven were Caucasian. Ten of the total 12 donors demonstrated an increase in BNP levels compared to pre-stimulation results. Follow-up of four total donors 9-17 days after donation demonstrated return of BNP levels to baseline. None of the donors had clinical evidence of heart failure during stimulation, donation, or follow-up. The average increase in BNP was 4.2 fold, and in a total of 3 donors it exceeded the normal range for the laboratory. The presence or degree of BNP elevation did not correlate with age, gender, severity of GCSF side effects, liver panel results, or pre-apheresis peripheral CD34+ count.Conclusion:This case and preliminary study indicate that an increase in BNP levels can be observed in approximately 80% of HPC donors stimulated with 5 days of 10mcg/kg GCSF. The increase in BNP in these donors is not associated with ventricular dysfunction or symptoms of cardiac congestion, and it returns to baseline levels in 2-4 weeks. Two possible molecular mechanisms for this BNP increase include 1) activation of gp130 by increased circulating cytokines associated with GCSF; or 2) direct transcriptional activation of the BNP gene by cardiomyocyte GCSF receptor activation of the JAK-STAT pathway. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Prognostic role of N-terminal pro-brain natriuretic peptide in asymptomatic hypertensive and diabetic patients in primary care: impact of age and gender : Results from the PROBE-HF study.

The association between natriuretic peptides and clinical outcome in asymptomatic hypertensive and diabetic patients with no clinical evidence of heart failure (HF) is still unclear. We assessed the prognostic value of NT-pro BNP, and its interactions with age and gender, in a cohort of asymptomatic, stage A/B HF hypertensive and diabetic patients enrolled in primary care. NT-proBNP was measured in 1012 asymptomatic subjects with systemic hypertension and/or type-2 diabetes (age 66.6±7.8years, 48% males) with no clinical evidence of HF. Patients were prospectively followed over 49.8±6.7months for the development of cardiac death, HF hospitalization, and nonfatal myocardial infarction. Patients with NT-proBNP above the 80th age- and gender-specific percentile showed a threefold risk of events as compared to those with NT-proBNP under this cut-off [hazard ratio 3.2 (2.6-8.3), p<0.0001]. In multivariable analysis, NT-proBNP added independent and incremental prognostic information to a predictive model including established risk factors (p<0.0001). After stratification by age, increased NT-proBNP predicted outcome among patients in the second and third age tertiles, but not among those in the first tertile. Increased NT-proBNP was associated with a 3.6-fold risk in women and a 2.9-fold risk in men. Addition of the gender-NT-proBNP interaction to prognostic models further improved prediction of events (p=0.014). NT-proBNP measurement adds independent and incremental information for the prediction of clinical outcome in asymptomatic, stage A-B HF hypertensive and diabetic patients taken from primary care. This prognostic value might be further evident in the elderly and among women.

Cardiac effects of mitoxanthrone therapy in patients with multiple sclerosis.

Mitoxanthrone (MTX) is a synthetic anthracycline antibiotic that has been used for several years in the treatment of patients with primary progressive, secondary progressive, and relapsing remitting multiple sclerosis (MS) who do not respond to other drugs. MTX has antineoplastic, immunomodulatory, and antibacterial properties. The most common adverse effects of MTX include nausea and vomiting, hair loss, increased risk of urinary and respiratory tract infections, and amenorrhea. Less frequent problems include leukopenia, thrombocytopenia, anaemia, and an increase in hepatic enzyme and bilirubin levels. Other severe sequelae of MTX treatment are drug cardiotoxicity and a potential to induce leukaemia. Drug toxicity results from its affinity to iron ions. The resulting complex strongly induces formation of free oxygen radicals and increases lipid peroxidation. Asymptomatic reduction in left ventricular ejection fraction (LVEF) by two-dimensional (2D) echocardiography, cardiomyopathy, and congestive heart failure have been observed in patients with MS at a rate of about 2.6-5%. Few studies evaluated cardiotoxicity of MTX in MS patients. Most previous studies were performed in small groups of cancer patients and cardiac evaluation was limited to physical examination. To evaluate the effect of MTX treatment on LVEF by 2D echocardiography. We studied 72 MS patients aged 25-63 years who were treated with MTX in 2002-2014. The diagnosis of MS was made using the 2001 McDonald criteria updated in 2005. The study group included primary progressive MS in 40 (56%) patients, secondary progressive MS in 5 (7%) patients, and relapsing remitting MS in 27 (37%) patients. MTX was administered at 12 mg/m2 of body surface area every 3 months (up to the total dose of 140 mg/m2). MTX treatment was initiated in patients with no signs of heart failure on physical examination, normal electrocardiogram (ECG), normal LVEF by 2D echocardiography, and normal laboratory test findings including complete blood count and hepatic and renal function parameters. Each MTX administration was preceded by 2D echocardiography with LVEF measurement, ECG, and physical examination of the cardiovascular system. The effect of MTX treatment on LVEF was evaluated by comparing baseline LVEF with LVEF measurements before the last MTX dose. Statistical analysis was performed using the Student t test. The mean LVEF before administration of the first MTX dose was 65 ± 3.3%. The lowest LVEF at the final 2D echo-cardiographic examination was 60 ± 2.1%. We did not find a significant LVEF reduction during MTX treatment in MS patients compared to baseline values. Severe myocardial dysfunction manifesting with significant LVEF reduction by 2D echocardiography or clinical evidence of heart failure was not noted in any patient in the study group. Our study showed no significant LVEF reduction during MTX monotherapy in MS patients without a history of a cardiac disease and with normal echocardiographic findings at baseline. Long-term cardiac effects of MTX require further studies.

The effect of acceptance of illness on the quality of life in patients with chronic heart failure.

Although important, a relationship between acceptance of illness and quality of life has not been studied extensively in individuals with chronic heart failure. The aim of this study was to analyse an association between these two variables in a large group of individuals with at least a six-month history of heart failure. The study included 100 patients (68 men and 32 women, mean age 63.2±12.2 years) with at least six months' clinical evidence of heart failure corresponding to New York Heart Association class II, III or IV. All the patients were examined with the Nottingham Health Profile (NHP) questionnaire and Acceptance of Illness Scale (AIS). The patients presenting with low levels of acceptance of illness (8-18 points) scored significantly higher on the energy, pain, emotional reaction, sleep, social isolation and mobility domains of the NHP. Multivariate analysis showed that acceptance of illness was the only independent predictor of quality of life in all the NHP domains: energy (β= -0.653, p<0.001), pain (β= -1.464, p<0.001), emotional reactions (β -1.738, p<0.001), sleep (β= -0.820, p<0.001), social isolation (β= -0.638, p<0.001) and mobility (β= -1.739, p<0.001). Male gender proved to be an independent predictor of lower pain scores (β= -1.320, p= 0.001) and divorce was associated with higher social isolation scores (β=1.948, p<0.001). The extent a patient accepts their chronic heart failure diagnosis has been shown to impact on their quality of life.

NT-proBNP linking low-moderately impaired renal function and cardiovascular mortality in diabetic patients: the population-based Casale Monferrato Study.

BackgroundFew data are available to assess whether a low-moderate reduction in estimated glomerular filtration rates (eGFR) has a role per se on cardiovascular (CV) mortality or other biomarkers such as NT-proBNP allow to explain such association.Methods and FindingsIn a prospective study including 1,645 type 2 diabetic subjects of the population-based Casale Monferrato Study, who had no clinical evidence of heart failure and eGFR >45 ml/min/1.73 m2, we examined 6 years CV mortality. Multivariate Cox proportional hazards modeling were used to estimate the effect of NT-proBNP on the association between eGFR and mortality, independently of baseline CV risk factors, albumin excretion rate (AER) and C-reactive protein (CRP). During follow-up, 327 people died (149 of CV diseases) out of 8334.5 person-years. Compared to eGFR≥90 ml/min/1.73 m2, values of 60–89 and 45–59 ml/min/1.73 m2 conferred a fully adjusted hazard ratios (HRs) of CV mortality of 1.74 (1.08–2.82) and 1.95 (1.03–3.68), respectively. After further adjustment for NT-proBNP, however, HRs were no longer significant (HRs 1.42, 0.83–2.42 and 1.22, 0.59–2.51). In this model, HR for logNT-proBNP was 1.84 (1.52–2.22). Adding NT-proBNP to the model improved the C-statistic of CV mortality from 0.79 (0.76–0.83) to 0.84 (0.81–0.87), yielded an IDI of 0.03 (p = 0.02), and a NRI of 0.44 (p = 0.016).ConclusionsIn diabetic people a modest reduction in renal function increased 6-year CV mortality independently of albuminuria. This association, however, was mainly explained by the effect of NT-proBNP, that remained the strongest prognostic marker for a worse CV outcome, even after adjustment for other CV risk factors and pre-existing CVD.

THERE IS NO CLINICAL JUSTIFICATION FOR CAROTID SCREENING IN MALES OVER 70 YEARS OR FEMALES OVER 75 YEARS

BACKGROUND: Acute pulmonary thromboembolism (APTE) is common and potentially life-threatening cardiovascular emergency. The fatality rate in acute cases ranges from 7-11%. There are many predisposing risk factors for APTE. Depressed, inactive patients would appear to be at significant risk for pulmonary embolism, given their lack of activity and putative platelet pathology. METHODS AND RESULTS: We report a clinical case of a 41 years old patient flowed for depression 4 months ago who reported that he spent almost all of his time in bed, sleeping with limited physical activity, that presenting at the emergency for acute onset of fatigue, shortness of breath and dyspnoea a few hours before admission, the anamnesis revealed no classical factors of veinous thromboembolism, the clinical examination fount a tachycardia, tachypnea, without clinical evidence of heart failure, the D-Dimer level was elevated, and the thoracic CT angiogram revealed intraluminal thrombi in lobar and segmental branches of the pulmonary arteries causing incomplete luminal obstruction. Diagnosis of APTE was confirmed, further etiological investigations ruled out other etiology of the venous thromboembolism. the patient was treated by anticoagulant, and antidepressant therapy with good clinical improvement. CONCLUSION: Severe major depression associated with psychomotor retardation and immobility can be a risk factor for pulmonary embolism. We must remember to search a depression in patients with pulmonary embolism and may be use a prophylaxis for this kind of patients.