Echocardiographic parameters associated with less reverse left ventricular remodeling after transcatheter aortic valve implant in subjects with prosthesis patient mismatch.

BACKGROUND: Transaortic valve implant (TAVI) is the treatment of choice for severe aortic stenosis (AS). Some patients develop prosthesis patient mismatch (PPM) after TAVI. It is challenging to determine which patients are at risk for clinical deterioration. METHODS: We retrospectively measured echocardiographic parameters of left ventricular (LV) morphology and function, prosthetic aortic valve effective orifice area (iEOA) and hemodynamics in 313 patients before and 1 year after TAVI. Our objective was to compare the change in echocardiographic parameters associated with left ventricular reverse modeling in subjects with and without PPM. Our secondary objective was to evaluate echo parameters associated with PPM and the relationship to patient functional status and survival post-TAVI. RESULTS: We found that 82 (26.2%) of subjects had moderate and 37 (11.8%) had severe PPM post-TAVI. There was less relative improvement in LVEF with PPM (1.9 ± 21.3% vs. 8.2 + 30.1%, p = .045). LV GLS also exhibited less relative improvement in those with PPM (13.4 + 34.1% vs. 30.9 + 73.3%, p = .012). NYHA functional class improved in 84.3% of subjects by one grade or more. Echocardiographic markers of PPM were worse in those without improvement in NYHA class (mean AT/ET was .29 vs. .27, p = .05; DVI was .46 vs. .51, p = .021; and iEOA was .8 cm/m2 vs. .9 cm/m2 , p = .025). There was no association with PPM and survival. CONCLUSIONS: There was no improvement in LVEF and less improvement in LV GLS in those with PPM post-TAVI. Echocardiographic markers of PPM were present in those with lack of improvement in NYHA functional class.

Risk factors for asymptomatic echocardiographic abnormalities that predict symptomatic heart failure.

AIMS: Risk factors for asymptomatic echocardiographic abnormalities that predict symptomatic heart failure (HF) may provide insight into early mechanisms of HF pathogenesis. We examined risk factors associated with asymptomatic echocardiographic structural, systolic, and diastolic abnormalities, separately and in combination, and interactions between risk factors, in the prospective community-based SCReening Evaluation of the Evolution of New HF (SCREEN-HF) Study cohort of 3190 participants at increased risk of cardiovascular disease. METHODS AND RESULTS: Inclusion criteria were age ≥ 60 years with one or more of hypertension, diabetes, ischaemic heart disease, valvular heart disease, abnormal heart rhythm, cerebrovascular disease, or renal impairment. Exclusion criteria were known HF, ejection fraction < 50%, or >mild valve abnormality. Structural, systolic, and diastolic echocardiographic abnormalities were defined according to the Atherosclerosis Risk in Communities study criteria, and risk factors for asymptomatic structural, systolic, and diastolic abnormalities were identified using logistic regression analysis. In multivariable analysis, increased body mass index (BMI), non-steroidal anti-inflammatory drug therapy, and alcohol intake were risk factors for isolated structural abnormality, whereas male gender, increased heart rate, atrial fibrillation (AF), angiotensin-converting enzyme inhibitor therapy, and obstructive sleep apnoea were associated with a lower risk. Moreover, male gender, smoking, increased systolic blood pressure, and physical inactivity were risk factors for isolated systolic abnormality, whereas increased pulse pressure and antihypertensive therapy were associated with a lower risk. Furthermore, increased age, blood pressure, amino-terminal pro-B-type natriuretic peptide level, and warfarin therapy (associated with AF) were risk factors for isolated diastolic abnormality, whereas increased heart rate and triglyceride level (associated with BMI) were associated with a lower risk. The association of increased heart rate with lower risk of structural and diastolic abnormalities was independent of ß-blocker therapy. Interactions between risk factors differed for structural, systolic, and diastolic abnormalities. CONCLUSIONS: The different risk factors for asymptomatic structural, systolic, and diastolic abnormalities that predict symptomatic HF, and the interactions between risk factors, illustrate how these structural, systolic, and diastolic abnormalities represent unique trajectories that lead to symptomatic HF. Improved understanding of these trajectories may assist in the design of HF prevention strategies.

Circulating Biomarkers for Cardiotoxicity Risk Prediction.

OPINION STATEMENT: Improvements in cancer survival have led to the emergence of cardiovascular disease as an important determinant of adverse outcome in survivors. Cancer therapeutics-related cardiac dysfunction is the most well-known form of cardiotoxicity. However, newer cancer therapies bring a broader range of cardiotoxicities. The optimal method to identify patients at risk of these complications is unclear, but circulating biomarkers comprise one possible approach. Troponins and natriuretic peptides have garnered the broadest evidence base for cardiotoxicity risk prediction, but other markers are being investigated. In this review, we explore evidence for circulating biomarkers in cardiotoxicity prediction associated with cancer therapies.

Kidney age - chronological age difference (KCD) score provides an age-adapted measure of kidney function.

BACKGROUND: Given the age-related decline in glomerular filtration rate (GFR) in healthy individuals, we examined the association of all-cause death or cardiovascular event with the Kidney age - Chronological age Difference (KCD) score, whereby an individual's kidney age is estimated from their estimated GFR (eGFR) and the age-dependent eGFR decline reported for healthy living potential kidney donors. METHODS: We examined the association between death or cardiovascular event and KCD score, age-dependent stepped eGFR criteria (eGFRstep), and eGFR < 60 ml/min/1.73 m2 (eGFR60) in a community-based high cardiovascular risk cohort of 3837 individuals aged ≥60 (median 70, interquartile range 65, 75) years, followed for a median of 5.6 years. RESULTS: In proportional hazards analysis, KCD score ≥ 20 years (KCD20) was associated with increased risk of death or cardiovascular event in unadjusted analysis and after adjustment for age, sex and cardiovascular risk factors. Addition of KCD20, eGFRstep or eGFR60 to a cardiovascular risk factor model did not improve area under the curve for identification of individuals who experienced death or cardiovascular event in receiver operating characteristic curve analysis. However, addition of KCD20 or eGFR60, but not eGFRstep, to a cardiovascular risk factor model improved net reclassification and integrated discrimination. KCD20 identified individuals who experienced death or cardiovascular event with greater sensitivity than eGFRstep for all participants, and with greater sensitivity than eGFR60 for participants aged 60-69 years, with similar sensitivities for men and women. CONCLUSIONS: In this high cardiovascular risk cohort aged ≥60 years, the KCD score provided an age-adapted measure of kidney function that may assist patient education, and KCD20 provided an age-adapted criterion of eGFR-related increased risk of death or cardiovascular event. Further studies that include the full age spectrum are required to examine the optimal KCD score cut point that identifies increased risk of death or cardiovascular event, and kidney events, associated with impaired kidney function, and whether the optimal KCD score cut point is similar for men and women. TRIAL REGISTRATION: ClinicalTrials.gov NCT00400257 , NCT00604006 , and NCT01581827 .

Utilizing left atrial strain to identify patients at risk for atrial fibrillation on ibrutinib.

BACKGROUND: Ibrutinib is associated with atrial fibrillation (AF), though echocardiographic predictors of AF have not been studied in this population. We sought to determine whether left atrial (LA) strain on transthoracic echocardiography could identify patients at risk for developing ibrutinib-related atrial fibrillation (IRAF). METHODS: We performed a retrospective review of 66 patients who had an echocardiogram prior to ibrutinib treatment. LA strain was measured with TOMTEC Imaging Systems, obtaining peak atrial longitudinal strain (PALS) and peak atrial contraction strain (PACS) on 4-chamber and 2-chamber views. Statistical analysis was performed with chi-square analysis, t test, or binomial regression analysis, with a P-value < .05 considered statistically significant. RESULTS: Twenty-two patients developed IRAF (33%). Age at initiation of ibrutinib was significantly associated with IRAF (65.1 years vs 74.1 years, P = .002). Mean ibrutinib dose was lower among patients who developed IRAF (388.2 ± 121.7 vs 448.6 ± 88.4, P = .025). E/e' was significantly higher among patients who developed IRAF (11.5 vs 9.3, P = .04). PALS was significantly lower in patients who developed AF (30.3% vs 36.3%, P = .01). On multivariate regression analysis, age, PALS, and PACS were significantly associated with IRAF. On multivariate regression analysis, only PACS remained significantly associated with IRAF while accounting for age. CONCLUSIONS: Age, ibrutinib dose, E/e', and PALS on pre-treatment echocardiogram were significantly associated with development of IRAF. On multivariate regression analyses, age, PALS, and PACS remained significantly associated with IRAF. Impaired LA mechanics add to the assessment of patients at risk for IRAF.

Inter-vendor variability and reproducibility of subcostal left ventricular longitudinal strain.

Left ventricular longitudinal strain (LVLS) performed using subcostal windows is a novel alternative for patients who require strain imaging but have poor apical windows. We investigated the reproducibility and inter-vendor variability of subcostal LVLS. One hundred and twenty-four echocardiographic studies were analysed from 73 women with early stage HER2-positive breast cancer. Speckle tracking strain was performed offline using EchoPAC and TomTec on subcostal 4-chamber and 3-chamber views to obtain subcostal 4-chamber (SC4_LS) and 3-chamber (SC3_LS) LVLS which was then averaged (SCav_LS). Reproducibility of subcostal single chamber and averaged LVLS were assessed. Measurements between platforms were compared. Strain was reported in absolute magnitude. EchoPAC measurements of SC3_LS (20.5 ± 2.4% vs. 21.2 ± 2.5%, p = 0.002) and SCav_LS (20.9 ± 2.1% vs. 21.2 ± 2.1%, p = 0.02) were lower than TomTec measurements while SC4_LS was similar (21.3 ± 2.7% vs. 21.3 ± 2.5%, p = 0.94). Mean differences between EchoPAC and TomTec were ≤ 0.6% strain units for all subcostal LVLS measurements; SCav_LS showed the narrowest limits of agreement (LOA) (mean difference - 0.3%, LOA - 3.2 to 2.6%). EchoPAC and TomTec measurements of SCav_LS showed good correlation (r = 0.76, p < 0.001). Intra-observer and inter-observer analysis showed good reproducibility. Inter-observer variability was lower than inter-vendor variability; SCav_LS was most reproducible: inter-observer relative mean error was 3.6% for EchoPAC and 4.3% for TomTec and inter-observer LOA were ± 2.1% for EchoPAC and ± 2.6% for TomTec. Averaged subcostal LVLS was highly reproducible with inter-observer variability comparable to GLS. Inter-vendor differences in averaged subcostal LVLS were small but statistically significant.

Mechanical Complications of Acute Myocardial Infarction: A Review.

Importance: Mechanical complications of acute myocardial infarction include left ventricular free-wall rupture, ventricular septal rupture, papillary muscle rupture, pseudoaneurysm, and true aneurysm. With the introduction of early reperfusion therapies, these complications now occur in fewer than 0.1% of patients following an acute myocardial infarction. However, mortality rates have not decreased in parallel, and mechanical complications remain an important determinant of outcomes after myocardial infarction. Early diagnosis and management are crucial to improving outcomes and require an understanding of the clinical findings that should raise suspicion of mechanical complications and the evolving surgical and percutaneous treatment options. Observations: Mechanical complications most commonly occur within the first week after myocardial infarction. Cardiogenic shock or acute pulmonary edema are frequent presentations. Echocardiography is usually the first test used to identify the type, location, and hemodynamic consequences of the mechanical complication. Hemodynamic stabilization often requires a combination of medical therapy and mechanical circulatory support. Surgery is the definitive treatment, but the optimal timing remains unclear. Percutaneous therapies are emerging as an alternative treatment option for patients at prohibitive surgical risk. Conclusions and Relevance: Mechanical complications present with acute and dramatic hemodynamic deterioration requiring rapid stabilization. Heart team involvement is required to determine appropriate management strategies for patients with mechanical complications after acute myocardial infarction.

Association of the H2FPEF Risk Score with Recurrence of Atrial Fibrillation Following Pulmonary Vein Isolation.

BACKGROUND: While atrial fibrillation (AF) and heart failure with preserved ejection fraction (HFpEF) commonly coexist, the efficacy of pulmonary vein isolation in the setting of HFpEF is unclear. METHODS: In a cohort of patients who underwent cryoballoon ablation (CBA) from 2011 to 2016, we calculated the H2FPEF risk score, a novel 6-item score (scale: 0-9 points) that accurately predicts the probability of HFpEF. We compared characteristics of patients by H2FPEF score and evaluated the association of H2FPEF score with 12-month recurrence of AF post-procedure. RESULTS: Of patients with available data to calculate the H2FPEF score (n=105), the median H2FPEF score was 5 (interquartile range: 4-6), corresponding to >80% probability of HFpEF. Compared to patients with H2FPEF scores ≤4 (n=34), patients with H2FPEF scores of 5 and 6 (n=46) and ≥7 (n=25) carried higher rates of hypertension (≤4: 21% vs. 5 and 6: 63% vs. ≥7: 88%, P<0.001) and diabetes (≤4: 0% vs. 5 and 6: 9% vs. ≥7: 32%, P=0.001). The overall 12-month recurrence rate of AF was 21%. There was no association between H2FPEF score and recurrence of AF at 12 months (OR per SD increase in log-H2FPEF score: 0.87, 95% CI: 0.54-1.40, P=0.57). CONCLUSIONS: Among patients undergoing CBA for AF, median H2FPEF scores are elevated, and screening for occult HFpEF may be warranted in this population. There was no association of the H2FPEF score and AF recurrence at 12 months, suggesting efficacy of CBA even among patients with high H2FPEF scores.

Inflammation-mediated age-dependent effects of casein kinase 2-interacting protein-1 on osteogenesis in mesenchymal stem cells.

BACKGROUND: The casein kinase 2-interacting protein-1 (CKIP-1) is important in the development of osteoblasts and cardiomyocytes. However, the effects of CKIP-1 on osteoblast precursor mesenchymal stem cells (MSCs) remain unclear. This study aimed to determine whether CKIP-1 affects osteogenic differentiation in MSCs and explore the relationship of CKIP-1 and inflammation. METHODS: Bone marrow MSCs of CKIP-1 wild type (WT) and knockout (KO) mice were cultivated in vitro. Cell phenotype was analyzed by flow cytometry, colony formation was detected to study the proliferative ability. Osteogenic and adipogenic induction were performed. The osteogenic ability was explored by alizarin red staining, alkaline phosphatase (ALP) staining and ALP activity detection. Quantitative real-time polymerase chain reaction (qRT-PCR) was carried out to determine the mRNA expression levels of osteoblast marker genes. The adipogenic ability was detected by oil red O staining. Content of the bone was analyzed to observe the differences of bone imaging parameters including trabecular bone volume/tissue volume (BV/TV), bone surface area fraction/trabecular BV, trabecular number (Tb.N), and trabecular spacing (Tb.sp). Interleukin (IL)-1ß was injected on WT mice of 2 months old and 18 months old, respectively. Difference in CKIP-1 expression was detected by RT-PCR and western blot. The relationship between CKIP-1 and inflammation was explored by RT-PCR and western blot. RESULTS: ALP assays, alizarin red staining, and qRT-PCR showed that MSCs derived from CKIP-1 KO mice exhibited a stronger capability for osteogenesis. Micro-computed tomography detection showed that among 18-month-old mice, CKIP-1 KO mice presented significantly higher bone mass compared with WT mice (P = 0.02). No significant difference was observed in 2-month-old mice. In vivo data showed that expression of CKIP-1 was higher in the bone marrow of aging mice than in young mice (4.3-fold increase at the mRNA level, P = 0.04). Finally, the expression levels of CKIP-1 in bone marrow (3.2-fold increase at the mRNA level, P = 0.03) and cultured MSCs were up-regulated on chronic inflammatory stimulation by IL-1ß. CONCLUSIONS: CKIP-1 is responsible for negative regulation of MSC osteogenesis with age-dependent effects. Increasing levels of inflammation with aging may be the primary factor responsible for higher expression levels of CKIP-1 but may not necessarily affect MSC aging.

Multimodality imaging to guide transcatheter treatment of severe degenerative tricuspid regurgitation with tricuspid valve-in-ring implantation and paravalvular leak closure.

Tricuspid valve (TV) degeneration after surgical repair with an annuloplasty ring is problematic as redo operation carries high mortality. This can be addressed with transcatheter therapies to implant a valve within in prior ring (tricuspid valve-in-ring). When an incomplete ring is present, paravalvular leak is commonly encountered after tricuspid valve-in-ring (TViR) implant; however, this can be addressed with paravalvular leak closure devices. Multimodality imaging including cardiac computed tomography and three-dimensional (3D) transesophageal echocardiography (TEE) are important for successful TViR implant. We report a case of tricuspid regurgitation after tricuspid repair with an incomplete annuloplasty ring and subsequent paravalvular leak closure.

Three-dimensional echocardiography for the assessment of the tricuspid valve.

Tricuspid valve pathology is increasingly recognized as an important contributor to patient morbidity. Accordingly, interest in transcatheter interventions for tricuspid valve disease has continued to grow. Echocardiographic imaging of the tricuspid valve has therefore become an integral component of patient assessment and the essential imaging modality for interventional procedures. The need for improved tricuspid valve imaging has highlighted the variability in tricuspid valve anatomy and the difficulties of using two-dimensional (2D) echocardiography alone to determine the location and type of tricuspid valve disease. Here, three-dimensional (3D) imaging using tools such as biplane imaging, multiplanar reconstruction and live 3D acquisition allow a more accurate and efficient evaluation of the tricuspid valve. The 3D imaging of the tricuspid valve is often focused on transesophageal echocardiography, but the more anterior location of the tricuspid valve also lends itself to assessment with transthoracic echocardiography. In this review, we will examine how 3D imaging can complement and enhance the information obtained from 2D echocardiography, and present novel applications for the quantitation of valvular disease and its utility in intraprocedural imaging.

Age-related longitudinal change in cardiac structure and function in adults at increased cardiovascular risk.

AIM: Heart failure (HF) incidence increases markedly with age. We examined age-associated longitudinal change in cardiac structure and function, and their prediction by age and cardiovascular disease (CVD) risk factors, in a community-based cohort aged ≥60 years at increased CVD risk but without HF. METHODS AND RESULTS: CVD risk factors were recorded in 3065 participants who underwent a baseline echocardiographic examination, of whom 2358 attended a follow-up examination 3.8 [median, inter-quartile range (IQR) 3.5, 4.2] years later. Median age was 71 (IQR 67, 76) years and 55% of participants were male. Age was associated with longitudinal increase in left ventricular (LV) mass index (LVMI); decrease in LV volumes; increase in LV ejection fraction; decrease in mitral annular systolic velocity; decrease in diastolic function (decreased mitral early diastolic annular velocity (e'); and increase in left atrial volume index, mitral peak early diastolic flow velocity (E)/e' ratio, and tricuspid regurgitant velocity (TRVmax ) in men and women, except for TRVmax in men). In multivariable analysis, longitudinal increase in LVMI was explained by CVD risk factors alone, whereas age, together with CVD risk factors, independently predicted longitudinal change in all other echocardiographic parameters. CVD risk factors were differentially associated with longitudinal change in different echocardiographic parameters. CONCLUSIONS: Whereas the increase in LVMI with age was explained by CVD risk factors alone, age, together with risk factors, independently predicted longitudinal change in all other echocardiographic parameters, providing evidence for age-specific mechanisms of change in cardiac structure and function as people age. Age-associated change in LVMI, LV volumes, and diastolic function resembled what might be expected for the evolution of HF with preserved ejection fraction. Given the differential association of different CVD risk factors with longitudinal change in different echocardiographic parameters, therapies aimed at attenuation of age-associated change in cardiac structure and function, and HF evolution, will likely need to address multiple CVD risk factors.

Optimal Imaging Guidance During Transcatheter Mitral Valve-in-Valve Replacement in Bioprostheses With Radiolucent Sewing Rings.

Transcatheter mitral valve-in-valve replacement (TMVR) offers a less invasive strategy for managing bioprosthetic mitral valve dysfunction. TMVR positioning is challenging in the setting of a radiolucent bioprosthetic sewing ring. We present 2 cases demonstrating the roles of fluoroscopy and echocardiography in guiding TMVR placement within bioprostheses with radiolucent sewing rings. (Level of Difficulty: Intermediate.).

Age-specific diastolic dysfunction improves prediction of symptomatic heart failure by Stage B heart failure.

AIMS: We investigated whether addition of diastolic dysfunction (DD) and longitudinal strain (LS) to Stage B heart failure (SBHF) criteria (structural or systolic abnormality) improves prediction of symptomatic HF in participants of the SCReening Evaluation of the Evolution of New Heart Failure study, a self-selected population at increased cardiovascular disease risk recruited from members of a health insurance fund in Melbourne and Shepparton, Australia. Both American Society of Echocardiography and European Association of Cardiovascular Imaging (ASE/EACVI) criteria and age-specific Atherosclerosis Risk in Communities (ARIC) study criteria, for SBHF and DD, and ARIC criteria for abnormal LS, were examined. METHODS AND RESULTS: Inclusion criteria were age ≥60 years with one or more of self-reported ischaemic or other heart disease, irregular or rapid heart rhythm, cerebrovascular disease, renal impairment, or treatment for hypertension or diabetes for ≥2 years. Exclusion criteria were known HF, or ejection fraction <50% or >mild valve abnormality detected on previous echocardiography or other imaging. Echocardiography was performed in 3190 participants who were followed for a median of 3.9 (interquartile range: 3.4, 4.5) years after echocardiography. Symptomatic HF was diagnosed in 139 participants at a median of 3.1 (interquartile range: 2.1, 3.9) years after echocardiography. ARIC structural, systolic, and diastolic abnormalities predicted HF in univariate and multivariable proportional hazards analyses, whereas ASE/EACVI structural and systolic, but not diastolic, abnormalities predicted HF. ARIC and ASE/EACVI SBHF criteria predicted HF with sensitivities of 81% and 55%, specificities of 39% and 76%, and C statistics of 0.60 (95% confidence interval: 0.57, 0.64) and 0.66 (0.61, 0.71), respectively. Adding ARIC DD to SBHF increased sensitivity to 94% with specificity of 24% and C statistic of 0.59 (0.57, 0.61), whereas addition of ASE/EACVI DD to SBHF increased sensitivity to 97% but reduced specificity to 9% and the C statistic to 0.52 (0.50, 0.54, P < 0.0001). Addition of LS to ARIC or ASE/EACVI SBHF criteria had minimal impact on prediction of HF. CONCLUSIONS: Age-specific ARIC DD criteria, but not ASE/EACVI DD criteria, predicted symptomatic HF, and addition of age-specific ARIC DD criteria to ARIC SBHF criteria improved prediction of symptomatic HF in asymptomatic individuals with cardiovascular disease risk factors. Addition of LS to ASE/EACVI or ARIC SBHF criteria did not improve prediction of symptomatic HF.

Threshold body mass index and sex-specific waist circumference for increased risk of heart failure with preserved ejection fraction.

BACKGROUND: Body mass index †Deceased. (BMI) is a risk factor for heart failure with preserved ejection fraction (HFpEF). DESIGN: We investigated the threshold BMI and sex-specific waist circumference associated with increased HFpEF incidence in the SCReening Evaluation of the Evolution of New Heart Failure (SCREEN-HF) study, a cohort study of a community-based population at increased cardiovascular disease risk. METHODS: Inclusion criteria were age ≥60 years with one or more of self-reported hypertension, diabetes, heart disease, abnormal heart rhythm, cerebrovascular disease or renal impairment. Exclusion criteria were known heart failure, ejection fraction <50% or more than mild valve abnormality. Among 3847 SCREEN-HF participants, 73 were diagnosed with HFpEF at a median of 4.5 (interquartile range: 2.9-5.5) years after enrolment. RESULTS: HFpEF incidence rates were higher for BMI ≥27.5 kg/m2 than for BMI < 25 kg/m2, and for waist circumference >100 cm (men) or > 90 cm (women) than for waist circumference ≤94 cm (men) or ≤ 83 cm (women) in Poisson regression analysis. Semiparametric proportional hazards analyses confirmed these BMI and waist circumference thresholds, and exceeding these thresholds was associated with an attributable risk of HFpEF of 44-49%. CONCLUSIONS: Both central obesity and overweight were associated with increased HFpEF incidence. Although a randomised trial of weight control would be necessary to establish a causal relationship between obesity/overweight and HFpEF incidence, these data suggest that maintenance of BMI and waist circumference below these thresholds in a community similar to that of the SCREEN-HF cohort may reduce the HFpEF incidence rate by as much as 50%.

Prediction of incident heart failure by serum amino-terminal pro-B-type natriuretic peptide level in a community-based cohort.

AIMS: We investigated which serum amino-terminal pro-B-type-natriuretic peptide (NT-proBNP) levels inform heart failure (HF) risk in a community-based population at increased cardiovascular disease (CVD) risk. METHODS AND RESULTS: Inclusion criteria were age ≥ 60 years with one or more of self-reported hypertension, diabetes, heart disease, abnormal heart rhythm, cerebrovascular disease, or renal impairment. Exclusion criteria were known HF, ejection fraction (EF) < 50%, or more than mild valve abnormality. NT-proBNP levels were measured in 3842 participants on enrolment. HF was diagnosed in 162 participants at a median of 4.5 (interquartile range 2.7-5.4) years after enrolment, 73 with HF with preserved EF (HFpEF), 53 with HF with reduced EF (HFrEF), and 36 with valvular HF (VHF). Areas under the receiver operating characteristic curve (AUC) for 5-year prediction of total HF were similar for NT-proBNP alone (0.79, 95% confidence interval 0.74-0.83) and a 7-parameter multivariable model (0.82, 0.77-0.86, P = 0.035). NT-proBNP cut-points of 11, 16, and 25 pmol/L for individuals aged 60-69, 70-79, and ≥ 80 years, respectively, achieved sensitivities > 76% and specificities of 47-69% for 5-year prediction of total HF in men and women in all three age groups. Sensitivities were ≥ 75% in most subgroups according to body mass index, estimated glomerular filtration rate, and the presence or absence of atrial fibrillation, pacemaker, or CVD, and for the prediction of HFpEF, HFrEF and VHF. CONCLUSION: Age-specific serum NT-proBNP levels inform prognosis, and hence therapeutic decisions, regarding HF risk in individuals at increased CVD risk.

Risk factors for incident heart failure with preserved or reduced ejection fraction, and valvular heart failure, in a community-based cohort.

Background: The lack of effective therapies for heart failure with preserved ejection fraction (HFpEF) reflects an incomplete understanding of its pathogenesis. Design: We analysed baseline risk factors for incident HFpEF, heart failure with reduced ejection fraction (HFrEF) and valvular heart failure (VHF) in a community-based cohort. Methods: We recruited 2101 men and 1746 women ≥60 years of age with hypertension, diabetes, ischaemic heart disease (IHD), abnormal heart rhythm, cerebrovascular disease or renal impairment. Exclusion criteria were known heart failure, left ventricular ejection fraction <50% or valve abnormality >mild in severity. Median follow-up was 5.6 (IQR 4.6-6.3) years. Results: Median time to heart failure diagnosis in 162 participants was 4.5 (IQR 2.7-5.4) years, 73 with HFpEF, 53 with HFrEF and 36 with VHF. Baseline age and amino-terminal pro-B-type natriuretic peptide levels were associated with HFpEF, HFrEF and VHF. Pulse pressure, IHD, waist circumference, obstructive sleep apnoea and pacemaker were associated with HFpEF and HFrEF; atrial fibrillation (AF) and warfarin therapy were associated with HFpEF and VHF and peripheral vascular disease and low platelet count were associated with HFrEF and VHF. Additional risk factors for HFpEF were body mass index (BMI), hypertension, diabetes, renal dysfunction, low haemoglobin, white cell count and ß-blocker, statin, loop diuretic, non-steroidal anti-inflammatory and clopidogrel therapies, for HFrEF were male gender and cigarette smoking and for VHF were low diastolic blood pressure and alcohol intake. BMI, diabetes, low haemoglobin, white cell count and warfarin therapy were more strongly associated with HFpEF than HFrEF, whereas male gender and low platelet count were more strongly associated with HFrEF than HFpEF. Conclusions: Our data suggest a major role for BMI, hypertension, diabetes, renal dysfunction, and inflammation in HFpEF pathogenesis; strategies directed to prevention of these risk factors may prevent a sizeable proportion of HFpEF in the community. Trial registration number: NCT00400257, NCT00604006 and NCT01581827.

Risk factor management in a contemporary Australian population at increased cardiovascular disease risk.

BACKGROUND: Effective management of cardiovascular and chronic kidney disease risk factors offers longer, healthier lives and savings in healthcare. AIM: To examine risk factor management in participants of the SCReening Evaluation of the Evolution of New Heart Failure study, a self-selected population at increased cardiovascular disease risk recruited from members of a health insurance fund in Melbourne and Shepparton, Australia. METHODS: Inclusion criteria were age ≥ 60 years with one or more self-reported ischaemic or other heart diseases, irregular or rapid heart rhythm, cerebrovascular disease, renal impairment or treatment for hypertension or diabetes for ≥2 years. Exclusion criteria were known heart failure or cardiac abnormality on echocardiography or other imaging. Medical history, clinical examination, full blood examination and biochemistry (without lipids and glycated haemoglobin (HbA1c)) were performed for 3847 participants on enrolment, and blood pressure, lipids and HbA1c were measured 1-2 years after enrolment for 3203 participants. RESULTS: Despite 99% of 3294 participants with hypertension receiving antihypertensive medication, half had blood pressures >140/90 mmHg. Approximately 77% of participants were overweight or obese, with one third being obese. Additionally, 74% of participants at high cardiovascular disease risk had low-density lipoprotein cholesterol levels ≥2 mmol/L, one third of diabetic participants had HbA1c >7%, 22% had an estimated glomerular filtration rate < 60 mL/min/1.73m2 , and substantial proportions had under-utilisation of antiplatelet therapy and anticoagulation for atrial fibrillation and were physically inactive. CONCLUSIONS: This population demonstrated substantial potential to reduce cardiovascular and renal morbidity and mortality and healthcare costs through more effective management of modifiable risk factors.