The purpose of this study was to analyze the potential usefulness and clinical relevance of adding left atrial (LA) strain to left atrial volume index (LAVI) in the detection of left ventricular ...diastolic dysfunction (LVDD) in patients with preserved left ventricular ejection fraction (LVEF).
Recent studies have suggested that LA strain could be of use in the evaluation of LVDD. However, the potential utility and clinical significance of adding LA strain to LAVI in the detection of LVDD remains uncertain.
Using 2-dimensional speckle-tracking echocardiography, we analyzed a population of 517 patients in sinus rhythm at risk for LVDD such as those with arterial hypertension, diabetes mellitus, or history of coronary artery disease and preserved LVEF.
In patients with LV diastolic alterations and estimated elevated LV filling pressures, the rate of abnormal LA strain was significantly higher than an abnormal LAVI (62.4% vs. 33.6%, p < 0.01). In line with this, in patients with normal LAVI, high rates of LV diastolic alterations and abnormal LA strain were present (rates 80% and 29.4%, respectively). In agreement with these findings, adding LA strain to LAVI in the current evaluation of LVDD increased significantly the rate of detection of LVDD (relative and absolute increase 73.3% and 9.9%; rate of detection of LVDD: from 13.5% to 23.4%; p < 0.01). Regarding the clinical relevance of these findings, an abnormal LA strain (i.e., <23%) was significantly associated with worse New York Heart Association functional class, even when LAVI was normal. Moreover, in a retrospective post hoc analysis an abnormal LA strain had a significant association with the risk of heart failure hospitalization at 2 years (odds ratio: 6.6 95% confidence interval: 2.6 to 16.6) even adjusting this analysis for age and sex and in patients with normal LAVI.
The findings from this study provide important insights regarding the potential usefulness and clinical relevance of adding LA strain to LAVI in the detection of LVDD in patients with preserved LVEF.
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Left ventricular filling pressure (LVFP) is a marker for diastolic dysfunction and heart failure (HF) with preserved ejection fraction (pEF). The interaction between arterial stiffness (AS) and ...elevated LVFP has not been sufficiently investigated. In 257 patients with preserved left ventricular ejection fraction (mean age: 66 years, 53% female, mean left ventricular ejection fraction: 61%) and at least one cardiovascular risk factor (eg, hypertension and diabetes) for the development of HF or a previous diagnosis of HF, LVFP was estimated in accordance with the recommendations of the American Society of Echocardiography (elevated when E/e' ≥ 13, left atrial volume index ≥ 34 mL/m2). LVFP was correlated with radial pulse wave analysis (augmentation index normalized by 75 b/min AIx@75) and carotid-femoral pulse wave velocity (cfPWV). Thirty-eight percent of patients demonstrated an elevated LVFP. These patients were significantly older (68.3 ± 7.4 vs. 63.5 ± 7.6 years, P < .001), demonstrated a higher body mass index (29.8 ± 4.6 vs. 28.0 ± 5.0; P < .01), presented more often with hypertension (89.7% vs. 73.1%, P < .01), hypercholesterolemia (32.0% vs. 21.3%, P < .05), dyspnea on exertion (28.4% vs. 16.6%, P < .05), and peripheral edema (25.3% vs. 10.2%, P < .01). cfPWV and AIx@75 and were significantly elevated in patients with elevated LVFP (12.2 ± 2.7 m/s vs. 10.5 ± 2.6 m/s, P < .001, an 29.2 ± 6.7% vs. 27.4 ± 6.7%, P < .05 respectively). cfPWV and AIx@75 were correlated with echocardiographic parameters, that is, posterior wall thickness (r = 0.292, P < .001; r = 0.167, P < .01), left ventricular mass index (r = 0.255, P < .001; r = −0.192, P < .01), e' (r = −0.508, P < .001; r = −0.159, P < .05), and E/e' (r = 0.380, P < .001; r = 0.200, P < .01). cfPWV correlated with left atrial volume index (r = 0.189, P < .05) and increasing E/A ratio (r = −0.334, P < .001). Multivariate linear regression analysis demonstrated age and PWV as most important and independent predictors of LVFP elevation in the cohort. Increased AS measured by cfPWV was associated with an elevated LVFP in patients with preserved systolic function. Whether targeting AS as a major component of diastolic dysfunction and HF with preserved ejection fraction needs to be further investigated.
•The interaction between arterial stiffness and elevated left ventricular filling pressure is not sufficiently investigated.•This is a study in patients with preserved left ventricular ejection fraction and at least one cardiovascular risk factor for the development or a previous diagnosis of heart failure.•Increased arterial stiffness measured by carotid-femoral pulse wave velocity is associated with an elevated left ventricular filling pressure.
Aim
Heart failure with preserved ejection fraction (HFpEF) is associated with myocardial remodelling including severe pro‐fibrotic changes contributing to an increase in left ventricular stiffness ...and diastolic dysfunction. Serum C‐terminal propeptide of procollagen type I (PIP) strongly correlates with the turnover of extracellular cardiac matrix proteins and fibrosis. Torasemide, but not furosemide, was described to reduce collagen type I synthesis in clinically unstable patients with heart failure with reduced ejection fraction. We evaluated whether its effect translated to HFpEF patients with type 2 diabetes mellitus (T2DM) and abnormal basal PIP levels.
Methods and results
We performed a relatively small, single‐centre, randomised, double‐blind, two‐arm parallel‐group, active controlled clinical trial in 35 HFpEF patients with T2DM to determine the effects of a 9‐month treatment with torasemide vs. furosemide on changes of serum PIP levels. Patients with increased PIP levels (≥110 ng/mL), or evidence of structural changes with a left atrial volume index (LAVI) >29 mL/m2 and abnormal PIP levels (≥70 ng/mL), were eligible to participate. Fifteen patients were female (42%), mean age was 69 years, body mass index was 34.7 kg/m2, 83% were in New York Heart Association class II/III. Echocardiographic characteristics showed a mean left ventricular ejection fraction of >60%, a left ventricular mass index >120 g/m2, an E/e' ratio of 14, and a LAVI of 40 mL/m2 with a NT‐proBNP of 174 ng/L and a 6‐minute walk distance of 421 m. Mean per cent change in PIP was 2.63 ± 5.68% (±SEM) in torasemide vs. 2.74 ± 6.49% in furosemide (P = 0.9898) treated patients. Torasemide was not superior to furosemide in improving functional capacity, diastolic function, quality of life, or neuroendocrine activation.
Conclusion
In this hypothesis‐generating, mechanistic trial in stable HFpEF patients with T2DM, neither long‐term administration of torasemide nor furosemide was associated with a significant effect on myocardial fibrosis, as assessed by serum PIP. Further studies are urgently needed in this field. More specific diuretic and anti‐fibrotic treatment strategies in T2DM and/or HFpEF are warranted.
Heart failure with preserved ejection fraction (HFpEF) is a common disease with high incidence and increasing prevalence. Patients suffer from functional limitation, poor health‐related quality of ...life, and reduced prognosis. A pilot study in a smaller group of HFpEF patients showed that structured, supervised exercise training (ET) improves maximal exercise capacity, diastolic function, and physical quality of life. However, the long‐term effects of ET on patient‐related outcomes remain unclear in HFpEF. The primary objective of the Exercise training in Diastolic Heart Failure (Ex‐DHF) trial is to investigate whether a 12 month supervised ET can improve a clinically meaningful composite outcome score in HFpEF patients. Components of the outcome score are all‐cause mortality, hospitalizations, NYHA functional class, global self‐rated health, maximal exercise capacity, and diastolic function. After undergoing baseline assessments to determine whether ET can be performed safely, 320 patients at 11 trial sites with stable HFpEF are randomized 1:1 to supervised ET in addition to usual care or to usual care alone. Patients randomized to ET perform supervised endurance/resistance ET (3 times/week at a certified training centre) for 12 months. At baseline and during follow‐up, anthropometry, echocardiography, cardiopulmonary exercise testing, and health‐related quality of life evaluation are performed. Blood samples are collected to examine various biomarkers. Overall physical activity, training sessions, and adherence are monitored and documented throughout the study using patient diaries, heart rate monitors, and accelerometers. The Ex‐DHF trial is the first multicentre trial to assess the long‐term effects of a supervised ET programme on different outcome measures in patients with HFpEF.
Aims
The purpose of this pilot study was to assess the potential usefulness of diastolic stress test (DST) echocardiography in patients with suspected heart failure with preserved ejection fraction ...(HFpEF).
Methods and results
Patients with suspected HFpEF (left ventricular ejection fraction ≥ 50%, exertional dyspnoea, septal E/e′ at rest 9–14, and N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) at rest < 220 pg/mL; n = 13) and a control group constituted from asymptomatic patients with arterial hypertension (n = 19) and healthy subjects (n = 18) were included. All patients were analysed by two‐dimensional and Doppler echocardiography at rest and during exercise (DST) and underwent cardiopulmonary exercise testing and NT‐proBNP analysis during exercise. HFpEF during exercise was defined as exertional dyspnoea and peak VO2 ≤ 20.0 mL/min/kg. In patients with suspected HFpEF at rest, 84.6% of these patients developed HFpEF during exercise, whereas in the group of asymptomatic patients with hypertension and healthy subjects, the rate of developed HFpEF during exercise was 0%. Regarding the diagnostic performance of DST to detect HFpEF during exercise, an E/e′ ratio >15 during exercise was the most accurate parameter to detect HFpEF (accuracy 86%), albeit a low sensitivity (45.5%). Nonetheless, combining E/e′ with tricuspid regurgitation (TR) velocity > 2.8 m/s during exercise provided a significant increase in the sensitivity to detect patients with HFpEF during exercise (sensitivity 72.7%, specificity 79.5%, and accuracy 78%). Consistent with these findings, an increase of E/e′ was significantly linked to worse peak VO2, and the combination of an increase of both E/e′ and TR velocity was associated with elevated NT‐proBNP values during exercise.
Conclusions
The findings of this pilot study suggest that DST using E/e′ ratio and TR velocity could be of potential usefulness to diagnose HFpEF during exercise in patients with suspected HFpEF at rest.
Abstract ▪914▪This icon denotes a clinically relevant abstract
In bcr-abl-positive CML first-line therapy with the second generation tyrosine kinase inhibitors (TKI) nilotinib or dasatinib results in ...superior response rates and prevention of transformation as compared to imatinib. Generally, these TKIs are associated with mild and reversible toxicities but recent reports have indicated an elevated risk of PAOD in patients (pts) treated with nilotinib (Aichberger et al. 2011, Tefferi et al. 2011, le Coutre et al. 2011, Quintás-Cardama et al. 2012). We therefore screened all 153 chronic phase CML pts at our center for PAOD by sequentially determining ABI, followed by duplex ultrasonography when indicated. Cardiovascular risk factors were assessed with a specific questionnaire and biochemical parameters associated with PAOD were analyzed. We here present a first interim analysis.
Overall, 146 of 153 pts were evaluable and categorized into five groups: (I) first-line imatinib (n = 53); (II) first-line nilotinib (n= 31); (III) second-line nilotinib (n = 32); (IV) previously exposed to nilotinib (n = 23) and (V) never treated with nilotinib and currently not on imatinib (n = 7).
A pathological ABI, defined as <0.9, occurred in 24/116 (21 %) of all examined patients, but was more frequent in pts on first-line (7/26; 27 %, p=0.0181) and second-line nilotinib (10/24; 42 %, p=0.0004) as compared to pts on first-line imatinib (3/45; 7 %) despite a significantly longer treatment on first-line imatinib (median 80.25 months, range 4 – 137) than on first-line nilotinib (median 25.48 months, range 5 – 49, p<0.001). Newly diagnosed PAOD defined as a peripheral vascular occlusive event or pathological duplex ultrasonography was observed in 13/146 (8.9 %) of all pts and was more frequent in pts on first-line nilotinib (3/31; 9.6%, p=0.1057), second-line nilotinib (5/32, 15.6 %, p=0.0166) or pts previously exposed to nilotinib (4/23; 17.4 %, p=0.0123) as compared to pts on first-line imatinib (1/53; 1.9 %). No substantial differences between the five groups with respect to clinical cardiovascular risk factors were observed. However, biochemical risk factor assessment showed significantly higher levels of cholesterol and LDL in pts receiving first-line (218.0 mg/dl, p< 0.001, and 135.5 mg/dl, p< 0.01) and second-line nilotinib (219.9 mg/dl, p < 0.001, and 138.9 mg/dl, p < 0.01) as compared to pts on first-line imatinib (167.2 mg/dl and 97.8 mg/dl).
Of 16 pts with PAOD under or after nilotinib treatment, including three additional patients from a second center, 4 pts received nilotinib as first-line, 10 pts as second-line and 2 pts as third-line treatment. Median age was 62.4 years (range, 38–76) and median duration of CML was 103.1 months (range: 22–209). Best responses observed in this group of patients were CMR or MMR in 10/16 (62.5 %) and CCyR or MCyR in 6/16 (37.5 %) of patients. Major cardiovascular risk factors such as hypertension (13/15; 87), diabetes mellitus (5/14; 36 %), nicotine abuse (11/15; 73 %), cholesterol (5/12; 42 %) or LDL (6/13; 46 %) elevation were detectable in the majority. Vascular lesions affected the lower limb in 15/16 (94 %) and the eye in 1/16 pts (6 %). Cardiovascular interventions included percutaneous transluminal angioplasty (PTA) (7/16; 44 %), stent-implantation (5/16; 31 %) and/or surgery, including amputation (5/16; 31 %). Nilotinib was discontinued in 10/16 pts (63 %), dose-reduced in 5/16 pts (32 %) and continued in 1/16 pts (6 %).
Prospective monitoring of pts with CML in chronic phase by sequential evaluation of ABI and duplex ultrasonography revealed a significantly higher frequency of PAOD in pts on nilotinib than in pts on imatinib. Mechanisms leading to the development of PAOD under nilotinib treatment remain unknown. Aside from elevation of cholesterol and glucose levels not yet fully understood mechanisms such as inhibition of targets involved in vascular cell homeostasis (i.e. DDR1, KIT or PDGFR) must be considered. More prospective data is needed to determine the cardiovascular risk attributable to nilotinib. But at present, caution is advised in pts with ≥ 2 major risk factors or a known history of arteriopathy.
Rea:Bristol Myers-Squibb, Novartis, and Teva: Honoraria. le Coutre:Novartis: Research Funding, Speakers Bureau; BMS: Honoraria; Pfizer: Honoraria.
Aims
Heart failure with preserved ejection fraction (HFpEF) remains a common condition with no pharmacological treatment. Physical activity (PA) improves symptoms and quality of life (QoL), but no ...clear recommendations exist on PA in HFpEF patients. We investigated the association of PA (amount/intensity) on clinical phenotype in HFpEF.
Methods and results
The Aldosterone in Diastolic Heart Failure trial investigated spironolactone vs. placebo in stable HFpEF patients. At baseline, all patients underwent detailed phenotypization including echocardiography, cardiopulmonary exercise testing, 6 minute walking test (6MWT), and QoL assessment (36‐item Short‐Form questionnaire). PA was assessed by a self‐report questionnaire, classified in metabolic equivalents of task (MET) and analysed with regard to exercise capacity, diastolic function, and QoL. Four hundred twenty‐two patients (52% women, age 67 ± 8 years, New York Heart Association II and III) were classified by weekly MET hours into a low (<70), middle (70–140), or high (>140) level of PA. Total PA correlated positively with 6MWT distance (r = 0.17; P = 0.002) and physical function of QoL (r = 0.10; P = 0.05), but not with peak oxygen uptake (peakVO2). In contrast, both 6MWT distance and peakVO2 were significantly higher in patients who performed high‐intensity PA for >8 h/week (P < 0.001, P = 0.02, respectively). Time of high‐intensity PA was related to higher 6MWT distance (r = 0.21, P < 0.001), peakVO2, and better physical function of QoL (both r = 0.13, P = 0.01), whereas low‐intensity PA did not show significant associations. Interestingly, PA was not related to any measure of diastolic function.
Conclusions
A higher amount of PA is related to higher submaximal exercise capacity and physical function of QoL. Regarding maximal exercise capacity, only high‐intensity PA showed significant association in HFpEF patients.
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