Do Patients With Acute Heart Failure and Preserved Ejection Fraction Have Heart Failure at Follow-Up: Implications of the Framingham Criteria

BackgroundHeart failure (HF) with preserved ejection fraction (HFpEF) may be misdiagnosed. We assessed prevalence and consistency of Framingham criteria signs and symptoms in acute vs subsequent stable HFpEF.MethodsThree hundred ninety-nine patients with acute HFpEF according to Framingham criteria were re-assessed in stable condition. Four definitions of HFpEF at follow-up: (1) Framingham criteria alone, (2) Framingham criteria and natriuretic peptides (NPs), (3) Framingham criteria, NPs, and European Society of Cardiology HF guidelines echocardiographic criteria, (4) Framingham criteria, NPs, and the Efficacy and Safety of LCZ696 Compared to Valsartan, on Morbidity and Mortality in Heart Failure Patients With Preserved Ejection Fraction (PARAGON) trial echocardiographic criteria.ResultsAt follow-up, HFpEF was still present in 27%, 22%, 21%, and 22%, respectively. Most prevalent in acute HFpEF were dyspnea at exertion (90%), pulmonary rales (71%), persisting at follow-up in 70% and 13%, respectively. Characteristics at acute HF with greater or lesser odds of stable HFpEF; (1) jugular venous distention (odds ratio [OR] 1.80, 95% confidence interval [CI] 1.13–2.87; P = .013) and pleural effusion (OR 0.45, 95% CI 0.24–0.85; P = .014) and (4), older age (1.04, 95% CI 1.01–1.08; P = .014) and tachycardia (>100 bpm) 0.52, 95% CI 0.27–1.00; P = .048).ConclusionsIn patients with acute HFpEF, one-quarter met the HF definition according to Framingham criteria at ambulatory follow-up. The proportion of patients with postdischarge HFpEF was largely unaffected by additional echocardiographic or NP criteria Older age and jugular venous distention at acute presentation predicted persistent HFpEF at follow-up, whereas pleural effusion and tachycardia may yield false HFpEF diagnoses. This finding has implications for HFpEF trial design.     

Exercise Intolerance in Heart Failure With Preserved Ejection Fraction: Arterial Stiffness and Abnormal Left Ventricular Hemodynamic Responses During Exercise

BackgroundArterial stiffness is thought to contribute to the pathophysiology of heart failure with preserved ejection fraction (HFpEF). We sought to examine arterial stiffness in HFpEF and hypertension and investigate associations of arterial and left ventricular hemodynamic responses to exercise.Methods and ResultsA total of 385 symptomatic individuals with an EF of ≥50% underwent upright cardiopulmonary exercise testing with invasive hemodynamic assessment of arterial stiffness and load (aortic augmentation pressure, augmentation index, systemic vascular resistance index, total arterial compliance index, effective arterial elastance index, and pulse pressure amplification) at rest and during incremental exercise. An abnormal hemodynamic response to exercise was defined as a steep increase in pulmonary capillary wedge pressure relative to cardiac output (?PCWP/?CO > 2 mm Hg/L/min). We compared rest and exercise measures between HFpEF and hypertension in multivariable analyses. Among 188 participants with HFpEF (mean age 61 ± 13 years, 56% women), resting arterial stiffness parameters were worse compared with 94 hypertensive participants (mean age 55 ± 15 years, 52% women); these differences were accentuated during exercise in HFpEF (all P ≤ .0001). Among all participants, exercise measures of arterial stiffness correlated with worse ?PCWP/?CO. Specifically, a 1 standard deviation higher exercise augmentation pressure was associated with 2.15-fold greater odds of abnormal LV hemodynamic response (95% confidence interval 1.52–3.05; P < .001). Further, exercise measures of systemic vascular resistance index, elastance index, and pulse pressure amplification correlated with a lower peak oxygen consumption.ConclusionsExercise accentuates the increased arterial stiffness found in HFpEF, which in turn correlates with left ventricular hemodynamic responses. Unfavorable ventricular–vascular interactions during exercise in HFpEF may contribute to exertional intolerance and inform future therapeutic interventions.     

Multiple Prior Live Births Are Associated With Cardiac Remodeling and Heart Failure Risk in Women

ObjectiveGreater parity has been associated with cardiovascular disease risk. We sought to find whether the effects on cardiac remodeling and heart failure risk are clear.MethodsWe examined the association of number of live births with echocardiographic measures of cardiac structure and function in participants of the Framingham Heart Study (FHS) using multivariable linear regression. We next examined the association of parity with incident heart failure with preserved (HFpEF) or reduced (HFrEF) ejection fraction using a Fine-Gray subdistribution hazards model in a pooled analysis of n = 12,635 participants in the FHS, the Cardiovascular Health Study, the Multi-Ethnic Study of Atherosclerosis, and Prevention of Renal and Vascular Endstage Disease. Secondary analyses included major cardiovascular disease, myocardia infarction and stroke.ResultsAmong n = 3931 FHS participants (mean age 48 ± 13 years), higher numbers of live births were associated with worse left ventricular fractional shortening (multivariable β -1.11 (0.31); P = 0.0005 in ≥ 5 live births vs nulliparous women) and worse cardiac mechanics, including global circumferential strain and longitudinal and radial dyssynchrony (P < 0.01 for all comparing ≥ 5 live births vs nulliparity). When examining HF subtypes, women with ≥ 5 live births were at higher risk of developing future HFrEF compared with nulliparous women (HR 1.93, 95% CI 1.19–3.12; P = 0.008); by contrast, a lower risk of HFpEF was observed (HR 0.58, 95% CI 0.37–0.91; P = 0.02).ConclusionsGreater numbers of live births are associated with worse cardiac structure and function. There was no association with overall HF, but a higher number of live births was associated with greater risk for incident HFrEF.     

Sudden Cardiac Death in Heart Failure Patients With Preserved Ejection Fraction

BackgroundWhereas sudden cardiac death (SCD) risk has been recognized in heart failure (HF) patients with reduced ejection fraction (HFrEF), less is known about SCD risk in HF patients with preserved EF (HFpEF). We examined the incidence and predictors of SCD in HFpEF in a large population sample.Methods and ResultsMedical records of patients discharged with a primary diagnosis of HF from hospitals in Minneapolis–St Paul in 1995 and 2000 were abstracted. HFpEF was defined as EF ≥45%. SCD was defined as cardiac arrest or out-of-hospital death due to coronary heart disease (CHD) on death certificates. A total of 2,203 patients (age 70 ± 11 years, 53% male) were included. The 787 patients (36%) with HFpEF were older, more often female and more likely to have hypertension than the 1,416 (64%) with HFrEF. All-cause mortality (52% vs 58%; P = .01) and SCD (6% vs 14%; P < .0001) rates were lower in HFpEF than in HFrEF 5 years after hospital discharge. Age, sex, CHD, and length of index hospitalization were the only independent predictors of SCD in HFpEF.ConclusionsIncidence of SCD in HFpEF is lower than in HFrEF. Present markers of SCD in HFpEF are sparse and insufficient to identify the patient at risk.     

Prior Carpal Tunnel Syndrome and Early Concomitant Echocardiographic Findings Among Patients With Cardiac Amyloidosis

BackgroundWe aimed to characterize patients with systemic amyloidosis stratified by a prior diagnosis of carpal tunnel syndrome (CTS) and to describe early echocardiographic parameters concomitant with CTS.Methods and ResultsPatients with suspected amyloidosis during CTS diagnosis were excluded. Our cohort included 108 patients with systemic amyloidosis of which 36% had a prior CTS at a median of 4 years (interquartile range [IQR] 2.8–6.7 years) before disease diagnosis. Patients with prior CTS were more likely to present subsequently with cardiac amyloidosis (78% vs 53%, P = .013), yet overall survival was comparable between groups (53% vs 61%, P = .825). Prior CTS was more commonly diagnosed in subsequent patients with transthyretin (62%) than in patients with immunoglobulin light chain (24%, P < .001). Furthermore, in a subanalysis of patients subsequently diagnosed with cardiac amyloidosis, findings at CTS diagnosis (n = 17) demonstrated a mild increase in septal thickness 1.3 cm (IQR 1.2–1.5 cm), increased relative wall thickness 0.46 cm (IQR 0.45–0.58 cm), and increased left ventricular mass index 155 g/m²(IQR 92–177 g/m²) compared with age-adjusted normal range echocardiographic values. Doppler mitral flow data was supportive of left ventricular diastolic dysfunction.ConclusionsEarly echocardiographic findings at CTS diagnosis, preceding the diagnosis of cardiac amyloidosis by several years, are suggestive of increased wall thickness and diastolic dysfunction.     

Adverse Renal Response to Decongestion in the Obese Phenotype of Heart Failure With Preserved Ejection Fraction

BackgroundPatients with heart failure (HF) with preserved ejection fraction (HFpEF) and obesity display a number of pathophysiologic features that may render them more or less vulnerable to negative effects of decongestion on renal function, including greater right ventricular remodeling, plasma volume expansion and pericardial restraint. We aimed to contrast the renal response to decongestion in obese compared to nonobese patients with HFpEFMethods and ResultsNational Institutes of Health heart failure network studies that enrolled patients with acute decompensated HFpEF (EF ≥ 50%) were included (DOSE, CARRESS, ROSE, and ATHENA). Obese HFpEF was defined as a body mass index ≥ 30 kg/m². Compared to nonobese HFpEF (n = 118), patients with obese HFpEF (n = 214) were an average of 9 years younger (71 vs 80 years,< 0.001), were more likely to have diabetes (64% vs 31%, P< 0.001) but had less atrial fibrillation (56% vs 75%, P< 0.001). Renal dysfunction (glomerular filtration rate < 60 mL/min/1.73m²) was present in 82% of patients, and there was no difference at baseline between obese and nonobese patients. Despite similar weight loss through decongestive therapies, obese patients with HFpEF demonstrated greater rise in creatinine (Cr) and decline in glomerular filtration rate, with a 2-fold higher incidence of mild worsening renal function (rise in Cr ≥ 0.3 mg/dL) (28 vs 14%, P = 0.008) and a substantially greater increase in severe worsening of renal function (rise in Cr > 0.5 mg/dL) (9 vs 0%, P = 0.002).ConclusionsDespite being nearly a decade younger, obese patients with HFpEF experience greater deterioration in renal function during decongestion than do nonobese patients with HFpEF. Further study to elucidate the complex relationships between volume distribution, cardiorenal hemodynamics and adiposity in HFpEF is needed.     

Sex Differences in the Phenotype of Transthyretin Cardiac Amyloidosis Due to Val122Ile Mutation: Insights from Noninvasive Pressure–Volume Analysis

BackgroundTransthyretin cardiac amyloidosis (ATTR-CA) is an under-recognized cause of heart failure with preserved ejection fraction. In the United States, the valine-to-isoleucine substitution (Val122Ile) is the most common inherited variant. Data on sex differences in presentation and outcomes of Val122Ile associated ATTR-CA are lacking.Methods and ResultsIn a retrospective, single-center study of 73 patients diagnosed with Val122Ile associated ATTR-CA between 2001 and 2018, sex differences in clinical and echocardiographic data at the time of diagnosis were evaluated. Pressure–volume analysis using noninvasive single beat techniques was used to compare chamber performance. Compared with men (n = 46), women (n = 27) were significantly older at diagnosis, 76 years vs 69 years; P < .001. The end-systolic pressure–volume relationship, 5.1 mm Hg*m²/mL vs 4.3 mm Hg*m²/mL; P = .27, arterial elastance, 5.5 mm Hg*m²/mL vs 5.7 mm Hg*m²/mL; P = .62, and left ventricular capacitance were similar between sexes as was pressure–volume areas indexed to a left ventricular end-diastolic pressure of 30 mm Hg, a measure of overall pump function. The 3-year mortality rates were also similar, 34% vs 43%; P = .64.ConclusionsDespite being significantly older at time of diagnosis with Val122Ile associated ATTR-CA, women have similar overall cardiac chamber function and rates of mortality to men, suggesting a less aggressive disease trajectory. These findings should be confirmed with longitudinal studies.     

Dynamic Nature of Pulmonary Artery Systolic Pressure in Decompensated Heart Failure With Preserved Ejection Fraction: Role of Functional Mitral Regurgitation

BackgroundPulmonary hypertension (PH) is prevalent in decompensated heart failure with preserved ejection fraction (HFpEF). We investigated the effect of a return to a compensated state on pulmonary artery systolic pressure (PASP) and functional mitral regurgitation (FMR).Methods and ResultsTwo-dimensional Doppler echocardiography was prospectively performed before initiation of standard therapy and 48 hours later in 37 patients hospitalized for HFpEF-related dyspnea and in 26 patients hospitalized for non-HFpEF–related dyspnea. Left atrial volume index, and E/e′ ratio, and PASP were significantly greater and E-wave deceleration time significantly shorter in HFpEF than in non-HFpEF patients. Thirty-two of the 37 HFpEF had FMR on admission whereas none of the non-HFpEF patients had FMR. After 48 hours of therapy, the reduction in PASP was significantly greater in the 26 HFpEF patients who improved than in the 11 HFpEF patients who did not (?24 vs ?9 mm Hg, respectively; P < .0001), whereas PASP remained unchanged in non-HFpEF patients. The decrease in PASP correlated in HFpEF patients with reductions in blood pressure, heart rate, left ventricular end-diastolic volume, inferior vena cava diameter, E/A ratio, E/e′ ratio, mitral effective regurgitant orifice area (EROA), and E-wave deceleration time. The correlation between PASP and mitral EROA was the only one that remained significant by multivariate analysis.ConclusionsNoninvasive monitoring of PASP and FMR during an episode of HFpEF decompensation reveals that the return to a compensated state is associated with a significant reduction in PASP and FMR.     

Sedentary Time and Cumulative Risk of Preserved and Reduced Ejection Fraction Heart Failure: From the Multi-Ethnic Study of Atherosclerosis

BackgroundThis study examined the relationship between self-reported sedentary time (ST) and the cumulative risk of heart failure with preserved ejection fraction (HFpEF) and reduced ejection fraction (HFrEF) in a diverse cohort of U.S. adults 45–84 years of age.Methods and ResultsUsing data from the Multi-Ethnic Study of Atherosclerosis (MESA), we identified 6,814 subjects, all free of baseline cardiovascular disease. Cox regression was used to calculate the hazard ratios (HR) associated with risk of HFpEF and HFrEF. Weekly ST was dichotomized based on the 75th percentile (1890 min/wk). During ～11.2 years of follow-up there were 178 first incident HF diagnoses: 74 HFpEF and 69 HFrEF. Baseline ST >1890 min/wk was significantly associated with an increased risk of HFpEF (HR 1.87, 95% confidence interval [CI] 1.13–3.09, P = .01), but not of HFrEF. The relationship with HFpEF remained significant in fully adjusted models including physical activity and waist circumference (HR 2.16, 95% CI 1.23–3.78, P < .01). In addition, every 60-minute increase in weekly ST was associated with a 3% increased risk of HFpEF (HR 1.03, 95% CI 1.01–1.05, P < .01).ConclusionsSedentary time >1890 min/wk (～4.5 h/d) is a significant predictor of HFpEF, independently from physical activity and adiposity.     

H2FPEF Score Reflects the Left Atrial Strain and Predicts Prognosis in Patients With Heart Failure With Preserved Ejection Fraction

BackgroundThe H₂FPEF score is a validated algorithm for the diagnosis of heart failure with preserved ejection fraction (HFpEF). We investigated the associations of the H₂FPEF score with echocardiographic parameters and prognosis in patients with HFpEF admitted for acute heart failure.Methods and ResultsIn total, 4312 patients at 3 tertiary centers were identified. Among 1335 patients with HFpEF, the H₂FPEF score was available in 1105 patients (39% male) with a median age of 77 years (interquartile range 69–82). The median H₂FPEF score was 4 (interquartile range 3–6). Patients with higher H₂FPEF scores had worse left atrial (LA) size, peak atrial longitudinal strain of the left atrium, mitral E/e’ ratio, and peak tricuspid regurgitation velocity. Peak atrial longitudinal strain of the left atrium demonstrated a significant association with the H₂FPEF score, in patients without atrial fibrillation and those without atrial fibrillation. After adjustment for clinical factors and echocardiographic parameters, patients with higher H₂FPEF scores had a higher risk of mortality and hospitalization for heart failure, regardless of the presence of atrial fibrillation.ConclusionsThe H₂FPEF score reflects left atrial function in patients with HFpEF admitted for acute heart failure. This association supports the clinical usefulness of the H₂FPEF score as an indicator of diastolic dysfunction, a diagnostic algorithm for HFpEF, and a prognostic factor in patients with HFpEF.     

Acutely decompensated heart failure with preserved and reduced ejection fraction present with comparable haemodynamic congestion

Aims

Congestion is a central feature of acute heart failure (HF) and its assessment is important for clinical decisions (e.g. tailoring decongestive treatments). It remains uncertain whether patients with acute HF with preserved ejection fraction (HFpEF) are comparably congested as in acute HF with reduced EF (HFrEF). This study assessed congestion, right ventricular (RV) and renal dysfunction in acute HFpEF, HFrEF and non‐cardiac dyspnoea.

Methods and results

We compared echocardiographic and circulating biomarkers of congestion in 146 patients from the MEDIA‐DHF study: 101 with acute HF (38 HFpEF, 41 HFrEF, 22 HF with mid‐range ejection fraction) and 45 with non‐cardiac dyspnoea. Compared with non‐cardiac dyspnoea, patients with acute HF had larger left and right atria, higher E/e', pulmonary artery systolic pressure and inferior vena cava (IVC) diameter at rest, and lower IVC variability (all P < 0.05). Mid‐regional pro‐atrial natriuretic peptide (MR‐proANP) and soluble CD146 (sCD146), but not B‐type natriuretic peptide (BNP), correlated with echocardiographic markers of venous congestion. Despite a lower BNP level, patients with HFpEF had similar evidence of venous congestion (enlarged IVC, left and right atria), RV dysfunction (tricuspid annular plane systolic excursion), elevated MR‐proANP and sCD146, and renal impairment (estimated glomerular filtration rate; all P > 0.05) compared with HFrEF.

Conclusion

In acute conditions, HFpEF and HFrEF presented in a comparable state of venous congestion, with similarly altered RV and kidney function, despite higher BNP in HFrEF.

     

The ischemic etiology of heart failure in diabetics limits reverse left ventricular remodeling after cardiac resynchronization therapy

Aim of the StudyThe aim of this study was to evaluate reverse volumetric left ventricular (LV) remodeling after cardiac resynchronization therapy (CRT) in patients with heart failure (HF) with vs. without diabetes mellitus (DM).MethodsThe study comprised 130 consecutive patients with HF (mean age, 61±12 years) who underwent CRT. Thirty patients (23%) had DM [mean glycated haemoglobin (HbA_1c), 7.2±3.4%; 13 (43%) on insulin therapy]. Echocardiography, including tissue Doppler measurements, was performed before CRT and between 3 and 6 months after CRT. Echocardiographic response was defined as a >15% reduction in LV end-systolic volume (ESV).ResultsPatients with DM had more often hypertension (60% vs. 29%, P<.05) and ischemic HF etiology (87% vs. 51%, P<.05), but similar pre-CRT echocardiographic findings. After CRT, patients with DM had equal reductions in QRS duration and lateral-to-septal mechanical delay, but less improvement in LV ESV, mitral annular tissue velocity, the myocardial performance (or Tei) index and the E/E′ ratio (ratio of early transmitral peak filling velocity to early mitral annular peak diastolic velocity, an indicator of LV filling pressure). Patients without reverse volumetric LV remodeling had more often DM [hazard ratio (HR), 1.897; P=.042] and an ischemic HF etiology (HR, 2.308; P=.006). An ischemic HF etiology (HR, 2.119; P=.018) was the only independent predictor of poor reverse volumetric LV remodeling.ConclusionIschemic etiology of HF is an independent predictor of poor echocardiographic response to CRT. Patients with DM and HF have a relatively poor echocardiographic response to CRT most probably due to a high incidence of ischemic etiology of HF.     

Impact of Right Atrial Remodeling in Heart Failure With Preserved Ejection Fraction

BackgroundFew studies have investigated right atrial (RA) remodeling in heart failure (HF) with preserved ejection fraction (HFpEF). This study sought to characterize the RA remodeling in HFpEF and to determine its prognostic significance.Methods and ResultsPatients with HFpEF were classified based on the presence of RA enlargement (RA volume index >39 mL/m² in men and >33 mL/m² in women). Compared with patients with normal RA size (n = 234), patients with RA dilation (n = 67) showed a higher prevalence of atrial fibrillation (AF), worse right ventricular systolic function, more severe pulmonary hypertension, and a greater prevalence of mild tricuspid regurgitation, as well as impaired RA reservoir function, with increased hepatobiliary enzyme levels. AF was strongly associated with the presence of RA dilation (odds ratio [OR] 10.2, 95% confidence interval [CI] 4.00–26.1 in current AF vs no AF and odds ratio 3.38, 95% CI 1.26–9.07, earlier AF vs no AF). Patients with RA dilation had more than a two-fold increased risk of composite outcomes of all-cause mortality or HF hospitalization (adjusted hazard ratio 2.01, 95% CI 1.09–3.70, P = .02). The presence of RA dilation also displayed an additive prognostic value over left atrial dilation alone.ConclusionsThese data demonstrate that HFpEF with RA remodeling is associated with distinct echocardiographic features characterizing advanced right heart dysfunction with an increased risk of adverse outcomes.     

Vitamin D Levels in Black Americans and the Association With Left Ventricular Remodeling and Incident Heart Failure With Preserved Ejectin Fraction: The Jackson Heart Study

BackgroundIn observational studies, a lower serum vitamin D₃ concentration has been associated with an increased risk of cardiovascular disease. However, the associations between serum vitamin D₃ levels and left ventricular (LV) structure and heart failure with preserved ejection fraction (HFpEF) have not been well-characterized among Black Americans. The prevalence of vitamin D₃ deficiency is higher among Black Americans than in other race/ethnicity groups. We hypothesized that serum vitamin D₃ levels are associated with LV concentric remodeling and incident HFpEF in Black Americans.Methods and ResultsAmong 5306 Black Americans in the Jackson Heart Study cohort, we investigated the relationships between serum vitamin D₃ levels and LV structure and function, evaluated with echocardiography, and incident HF hospitalization, categorized as either HF with reduced EF (HFrEF; an EF of <50%) or HFpEF (an EF of ≥50%). After adjustment for possible confounding factors, lower vitamin D₃ levels were associated with greater relative wall thickness (β for 1 standard deviation [SD] increase –0.003, 95% confidence interval –0.005 to –0.000). Over a median follow-up period of 11 years (range 10.2–11.0 years), 340 participants developed incident HF (7.88 cases per 1000 person-years), including 146 (43%) HFrEF and 194 (57%) HFpEF cases. After adjustment, higher serum vitamin D₃ levels were associated with decreased hazard for HF overall (hazard ratio for 1 SD increase 0.88, 95% confidence interval 0.78–0.99) driven by a significant association with HFpEF (hazard ratio for 1 SD increase 0.84, 95% confidence interval 0.71–0.99).ConclusionsIn this community-based Black American cohort, lower serum vitamin D₃ levels were associated with LV concentric remodeling and an increased hazard for HF, mainly HFpEF. Further investigation is required to examine whether supplementation with vitamin D₃ can prevent LV concentric remodeling and incident HFpEF in Black Americans.     

Arterial Stiffness and Vascular Load in HFpEF: Differences Among Women and Men

BackgroundMechanisms underlying sex differences in heart failure with preserved ejection fraction (HFpEF) are poorly understood. We sought to examine sex differences in measures of arterial stiffness and the association of arterial stiffness measures with left ventricular hemodynamic responses to exercise in men and women.MethodsWe studied 83 men (mean age 62 years) and 107 women (mean age 59 years) with HFpEF who underwent cardiopulmonary exercise testing with invasive hemodynamic monitoring and arterial stiffness measurement (augmentation pressure [AP], augmentation index [AIx], and aortic pulse pressure [AoPP]). Sex differences were compared using multivariable linear regression. We examined the association of arterial stiffness with abnormal left ventricular diastolic response to exercise, defined as a rise in pulmonary capillary wedge pressure relative to cardiac output (?PCWP/?CO) ≥ 2 mmHg/L/min by using logistic regression models.ResultsWomen with HFpEF had increased arterial stiffness compared with men. AP was nearly 10 mmHg higher, and AIx was more than 10% higher in women compared with men (P < 0.0001 for both). Arterial stiffness measures were associated with a greater pulmonary capillary wedge pressure response to exercise, particularly among women. A 1-standard deviation higher AP was associated with > 3-fold increased odds of abnormal diastolic exercise response (AP: OR 3.16, 95% CI 1.34–7.42; P = 0.008 [women] vs OR 2.07, 95% CI 0.95–5.49; P = 0.15 [men]) with similar findings for AIx and AoPP.ConclusionsArterial stiffness measures are significantly higher in women with HFpEF than in men and are associated with abnormally steep increases in pulmonary capillary wedge pressure with exercise, particularly in women. Arterial stiffness may preferentially contribute to abnormal diastolic function during exercise in women with HFpEF compared with men.     

Predictors of thirty-day readmission in nonagenarians presenting with acute heart failure with preserved ejection fraction: a nationwide analysis

BACKGROUDAcute heart failure with preserved ejection fraction (HFpEF) is a common but poorly studied cause of hospital admissions among nonagenarians. This study aimed to evaluate predictors of thirty-day readmission, in-hospital mortality, length of stay, and hospital charges in nonagenarians hospitalized with acute HFpEF.METHODSPatients hospitalized between January 2016 and December 2018 with a primary diagnosis of diastolic heart failure were identified using ICD-10 within the Nationwide Readmission Database. We excluded patients who died in index admission, and discharged in December each year to allow thirty-day follow-up. Univariate regression was performed on each variable. Variables with P-value < 0.2 were included in the multivariate regression model. RESULTSFrom a total of 45,393 index admissions, 43,646 patients (96.2%) survived to discharge. A total of 7,437 patients (15.6%) had a thirty-day readmission. Mean cost of readmission was 43,265 United States dollars (USD) per patient. Significant predictors of thirty-day readmission were chronic kidney disease stage III or higher [adjusted odds ratio (aOR) = 1.20, 95% CI: 1.07−1.34,P = 0.002] and diabetes mellitus (aOR = 1.18, 95% CI: 1.07−1.29,P = 0.001). Meanwhile, female (aOR = 0.90, 95% CI: 0.82−0.99,P = 0.028) and palliative care encounter (aOR = 0.27, 95% CI: 0.21−0.34,P < 0.001) were associated with lower odds of readmission. Cardiac arrhythmia (aOR = 1.46, 95% CI: 1.11−1.93, P = 0.007) and aortic stenosis (aOR = 1.36, 95% CI: 1.05−1.76,P = 0.020) were amongst predictors of in-hospital mortality. CONCLUSIONSIn nonagenarians hospitalized with acute HFpEF, thirty-day readmission is common and costly. Chronic comorbidities predict poor outcomes. Further strategies need to be developed to improve the quality of care and prevent the poor outcome in nonagenarians.

By 2030, it is estimated that one every thirty-three patients will have the diagnosis of heart failure (HF). The projected cost estimates of treating HF are 160 billion United States dollars (USD) in direct costs. Because of the aging of the population, greater increase in HF prevalence will be seen in older adults. It is projected that the number of patients > 80 years with HF will grow by 66% by 2030. ^[1]HF incidence and prevalence rise dramatically with age due to structural and functional alterations in the cardiovascular system, making HF the most prevalent cardiovascular disease among elderly. HF was reported to be the second leading cause of hospitalization for patients aged 75 years and above from 2013 to 2018.^[2]Most elderly patients with HF have impaired left ventricular diastolic function without significant impairment in left ventricular systolic function, which is called heart failure with preserved ejection fraction (HFpEF).^[3–6] Increased levels of brain natriuretic peptide, older age, myocardial infarction history, and reduced diastolic function make the prognosis of HFpEF worse.^[7–9]Over the years, there have been advances in the treatment of HF, however, the mortality, hospitalization, and readmission rates are still high.In this study, we aimed to assess the predictors and causes of readmissions with acute HFpEF among nonagenarians in the United States, by using the National Readmission Database (NRD).     

Mid- to Late-Life Inflammation and Risk of Cardiac Dysfunction,HFpEF and HFrEF in Late Life

BackgroundEpidemiologic data supporting the association of accumulated inflammation from mid- to late life with late-life risk of cardiac dysfunction and heart failure (HF) is limited.Methods and ResultsAmong 4011 participants in the Atherosclerosis Risk in Communities study who were free of prevalent cardiovascular disease at study Visit 5, accumulated inflammation was defined as time-averaged high-sensitivity c-reactive protein (hsCRP) over 3 visits spanning 1990 to 2013. Associations with left ventricular (LV) function at Visit 5 and with incident adjudicated HF post Visit 5 were assessed using linear and Cox regression, adjusting for demographics and comorbidities. Higher accumulated hsCRP was associated with greater LV mass index, lower e’, higher E/e’, and higher adjusting for demographics (all P ≤0.01), but only with higher pulmonary artery systolic pressure after adjustment for comorbidities (P = 0.024). At 5.3 ± 1.2 year follow-up, higher accumulated hsCRP was associated with greater risk of incident HF (HR 1.31 [95% CI 1.18–1.47], P < 0.001), HFrEF (1.26 [1.05–1.52], P = 0.01), and HFpEF (1.30 [1.11–1.53], P = 0.001) in demographic-adjusted models, but not after adjustment for comorbidities (all P > 0.10). Only Visit 5 hsCRP remained associated with incident HF (1.12 [1.02–1.24], P = 0.02) after full adjustment.ConclusionsGreater accumulated inflammation is associated with worse LV function and heightened HF risk in late-life. These relationships are attenuated after adjusting for HF risk factors.     

Missense Genetic Variation of ICAM1 and Incident Heart Failure

BackgroundIntercellular adhesion molecule-1 (ICAM-1) is a cell surface protein that participates in endothelial activation and is hypothesized to play a central role in heart failure (HF). We evaluated associations of ICAM1 missense genetic variants with circulating ICAM-1 levels and with incident HF.Methods and ResultsWe identified 3 missense variants within ICAM1 (rs5491, rs5498 and rs1799969) and evaluated their associations with ICAM-1 levels in the Coronary Artery Risk Development in Young Adults Study and the Multi-Ethnic Study of Atherosclerosis (MESA). We determined the association among these 3 variants and incident HF in MESA. We separately evaluated significant associations in the Atherosclerosis Risk in Communities (ARIC) study. Of the 3 missense variants, rs5491 was common in Black participants (minor allele frequency [MAF] > 20%) and rare in other race/ethnic groups (MAF < 5%). In Black participants, the presence of rs5491 was associated with higher levels of circulating ICAM-1 at 2 timepoints separated by 8 years. Among Black participants in MESA (n = 1600), the presence of rs5491 was associated with an increased risk of incident HF with preserved ejection fraction (HFpEF; HR = 2.30; [95% CI 1.25–4.21; P = 0.007]). The other ICAM1 missense variants (rs5498 and rs1799969) were associated with ICAM-1 levels, but there were no associations with HF. In ARIC, rs5491 was significantly associated with incident HF (HR = 1.24 [95% CI 1.02 – 1.51]; P = 0.03), with a similar direction of effect for HFpEF that was not statistically significant.ConclusionsA common ICAM1 missense variant among Black individuals may be associated with increased risk of HF, which may be HFpEF-specific.     

Increased hematocrit before blood pressure in men who develop hypertension over 20 years

We have previously demonstrated that neurohormonal activity can predict left ventricular (LV) mass in men who developed hypertension over 20 years. The aim of the study was to investigate early markers of cardiac and hemorheological changes at baseline in these men, i.e., before a rise in blood pressure. Fifty-six middle-aged men were followed for 20 years; 22 were sustained hypertensives, 17 developed hypertension, and 17 were sustained normotensives. They were compared at baseline (42 years) and follow-up (62 years). We investigated Cornell voltage product and Sokolow-Lyon voltage, hematocrit (Hct), and echocardiographic LV parameters. There was no sign of LV hypertrophy by electrocardiography (ECG) at baseline. Baseline Hct discriminated between the groups (P= .015) and correlated to diastolic blood pressure (DBP) at baseline (r = 0.37, P= .006) and follow-up (r = 0.31, P= .020). Regression analysis identified baseline Hct as an independent correlate of DBP in the cohort at baseline when they were untreated (β = .33, P= .013, R² = 0.25), and of borderline significance at follow-up (β = .26, P= .060, R² = 0.12) despite possible interference by antihypertensive drugs. Hct was elevated at baseline compatible with the hypothesis that pathogenic hemorheological processes could be activated at the outset and prior to cardiac changes in men who later develop hypertension.     

Long-term Prognostic Significance of Admission Tricuspid Regurgitation Pressure Gradient in Hospitalized Patients With Heart Failure With Preserved Ejection Fraction: A Report From the Japanese Real-World Multicenter Registry

BackgroundDoppler-estimated peak systolic tricuspid regurgitation pressure gradient (TRPG) is a representative noninvasive parameter for evaluating pulmonary artery systolic pressure, which can be a determinant of adverse outcomes in chronic heart failure with preserved ejection fraction (HFpEF). However, the prognostic implications of TRPG at admission for hospitalized patients with HFpEF are undetermined.Methods and ResultsWe examined 469 consecutive hospitalized patients with decompensated HFpEF (left ventricular ejection fraction ≥ 50%) who underwent TRPG measurement at admission in our HFpEF multicenter registry. The primary outcome of interest was all-cause death. Admission TRPG was significantly correlated with estimated pulmonary capillary wedge pressure and left atrial dimension (r = 0.24, P < 0.001 and r = 0.21, P < 0.001, respectively). During a median follow-up period of 748 (IQR 540–820) days, 83 patients died. Higher TRPG was significantly associated with higher mortality compared to lower TRPG (log-rank; P = 0.007). Multivariable analysis revealed that elevated TRPG was an independent determinant of mortality (HR 1.02, 95% CI 1.01–1.04, P = 0.008) after adjustment for prespecified confounders and renal function.ConclusionsElevated TRPG at admission was an independent determinant of mortality in hospitalized patients with HFpEF, indicating that TRPG at admission could be a useful marker for risk stratification in these patients.