Takeki Suzuki

Resting Heart Rate and Long-term Outcomes Among the African American Population: Insights From the Jackson Heart Study.

Importance Increased resting heart rate is associated with worse outcomes in studies of mostly white populations, but its significance is not well established in African Americans persons whose cardiac comorbidities and structural abnormalities differ. Objective To study the prognostic utility of heart rate in a community-based African American cohort in the Jackson Heart Study. Design, Setting, and Participants A total of 5261 participants in the Jackson Heart Study, a prospective, community-based study in Jackson, Mississippi, were evaluated. Baseline heart rate was assessed by quintiles and as a continuous variable. All participants with baseline heart rate documented by a 12-lead electrocardiogram without pacing or atrial fibrillation noted on their baseline Jackson Heart Study examination were included in the study. Follow-up began September 26, 2000, and was completed December 31, 2011. Data analysis was performed from July to October 2015. Main Outcomes and Measures Unadjusted and adjusted associations between heart rate and all-cause mortality and heart failure hospitalization using Cox proportional hazards regression models. Results Of the 5261 individuals included in the analysis, 1921 (36.5%) were men; median (25th-75th percentile) age was 55.7 (45.4-64.8) years. Median (25th-75th percentile) baseline heart rate was 63 beats per minute (bpm) (57-71 bpm). The highest heart rate quintile (73-118 bpm) had higher rates of diabetes (398 [37.4%]; P < .001) and hypertension (735 [69.1%]; P < .001), higher body mass index (median [IQR], 32.4 [28.1-38.3]; P < .001), less physical activity (0 hours per week, 561 [52.8%]; P < .001), and lower &bgr;-blocker use (73 [6.9%]; P < .001) compared with lower quintiles. Caffeine intake (from 80.7 to 85.5 mg/d; P = .57) and left ventricular ejection fraction (from 62% to 62.3%; P = .01) were similar between groups. As a continuous variable, elevated heart rate was associated with increased mortality and heart failure hospitalizations, with adjusted hazard ratios for every 5-bpm increase of 1.14 (95% CI, 1.10-1.19) and 1.10 (95% CI, 1.05-1.16), respectively. Similar patterns were observed in comparisons between the highest and lowest quintiles. Conclusions and Relevance Higher baseline heart rate was associated with increased mortality and heart failure hospitalizations among African American participants in the Jackson Heart Study. These findings are similar to those seen in white populations, but further study is needed to understand whether African American individuals benefit from interventions targeting heart rate reduction.

Delayed Time to Peak Velocity Is Useful for Detecting Severe Aortic Stenosis

Background Time to peak velocity (TPV) is an echocardiographic variable that can be easily measured and reflects a late peaking murmur, a classic physical finding suggesting severe aortic stenosis (AS). The aim of this study was to investigate the usefulness of TPV to evaluate AS severity. Methods and Results This study included 700 AS patients, whose aortic valve area (AVA) was <1.5 cm2, and 200 control patients. The TPV was defined as the time from aortic valve opening to when the flow velocity across the aortic valve reaches its peak. AS severity was classified as follows: High gradient severe AS, mean pressure gradient ≥40 mm Hg and AVA index (AVAI) <0.6 cm2/m2; Low gradient severe AS, mean pressure gradient <40 mm Hg, AVAI <0.6 cm2/m2, and dimensionless index <0.25; moderate AS, mean pressure gradient <40 mm Hg, AVAI ≥0.6 cm2/m2. The area under the receiver operating characteristic curve of TPV to predict high gradient severe AS was 0.94 (95% CI: 0.92–0.97, P<0.001). TPV was significantly delayed in low gradient severe AS compared with moderate AS both in patients with preserved (102±13 ms versus 83±13 ms, P<0.001) and with reduced ejection fraction (110±18 ms versus 88±13 ms, P<0.001). Delayed TPV was associated with increased all‐cause mortality or need for aortic valve replacement after adjustment for confounders (hazard ratio for first quartile, reference is fourth quartile: 7.31, 95% CI 4.26–12.53, P<0.001). Conclusions TPV is useful to evaluate AS severity and predict poor prognosis of AS patients.

Kidney function and sudden cardiac death in the community: The Atherosclerosis Risk in Communities (ARIC) Study

BACKGROUND Individuals with chronic kidney disease, particularly those requiring dialysis, are at high risk of sudden cardiac death (SCD). However, comprehensive data for the full spectrum of kidney function and SCD risk in the community are sparse. Furthermore, newly developed equations for estimated glomerular filtration rate (eGFR) and novel filtration markers might add further insight to the role of kidney function in SCD. METHODS We investigated the associations of baseline eGFRs using serum creatinine, cystatin C, or both (eGFRcr, eGFRcys, and eGFRcr-cys); cystatin C itself; and β2-microglobulin (B2M) with SCD (205 cases through 2001) among 13,070 black and white ARIC participants at baseline during 1990-1992 using Cox regression models accounting for potential confounders. RESULTS Low eGFR was independently associated with SCD risk: for example, hazard ratio for eGFR <45 versus ≥90mL/(min 1.73m(2)) was 3.71 (95% CI 1.74-7.90) with eGFRcr, 5.40 (2.97-9.83) with eGFRcr-cys, and 5.24 (3.01-9.11) with eGFRcys. When eGFRcr and eGFRcys were included together in a single model, the association was only significant for eGFRcys. When three eGFRs, cystatin C, and B2M were divided into quartiles, B2M demonstrated the strongest association with SCD (hazard ratio for fourth quartile vs first quartile 3.48 (2.03-5.96) vs ≤2.7 for the other kidney markers). CONCLUSIONS Kidney function was independently and robustly associated with SCD in the community, particularly when cystatin C or B2M was used. These results suggest the potential value of kidney function as a risk factor for SCD and the advantage of novel filtration markers over eGFRcr in this context.

Physical Activity Is Associated With Reduced Left Ventricular Mass in Obese and Hypertensive African Americans

BACKGROUND Physical activity (PA) has been associated with decreased left ventricular (LV) hypertrophy in previous studies. However, little is known about the relationship between PA and LV structure and factors which influence this relationship among African Americans. METHODS We evaluated 1,300 African Americans with preserved LV ejection fraction (EF > 50%) from the Genetic Epidemiology Network of Arteriopathy (GENOA) Study (mean age 62.4 years, 73% women). PA index was calculated as 3 * heavy activity hours + 2 * moderate activity hours + slight activity hours/day. The relationship between PA index and LV structure was evaluated using generalized estimating equation. The association between PA index and LV mass index by age group, sex, body mass index (BMI), history of hypertension, diabetes or coronary heart disease, estimated glomerular filtration rate, and current smoking status were plotted. RESULTS After adjustment for these factors, higher PA index was independently associated with lower LV mass index (P < 0.05). There were significant interactions between PA index and obesity (BMI ≥ 30) and history of hypertension on LV mass index (P for interaction <0.05, for both). Higher PA index was associated with lower LV mass index more in obese or hypertensive participants compared with nonobese or nonhypertensive participants. CONCLUSIONS Higher PA index was associated with reduced LV hypertrophy in obese and hypertensive African Americans. Prospective studies aimed at assessing whether increasing PA prevents LV hypertrophy and potentially reduces the risk of heart failure in these at risk groups are warranted.

Higher plasma leptin levels are associated with reduced left ventricular mass and left ventricular diastolic stiffness in black women: insights from the Genetic Epidemiology Network of Arteriopathy (GENOA) study

Our previous experimental animal data suggest a beneficial effect of leptin on LV structure and function. We hypothesized that leptin levels are associated with lower LV mass and myocardial stiffness which are important risk factors for the development of heart failure with preserved ejection fraction (HFpEF). We evaluated 1172 blacks, in which the prevalence of HFpEF is quite high, with preserved LV ejection fraction (EF > 50%) from the Genetic Epidemiology Network of Arteriopathy Study (mean age 62.9 years, 72% women), a community-based study to identify genes influencing blood pressure and target organ damage due to hypertension. Associations between leptin levels and indices of LV structure and function were evaluated using generalized estimating equations accounting for clustering in siblings. LV myocardial stiffness was evaluated using diastolic wall strain (DWS) measured by echocardiography. Analyses were stratified by sex because leptin levels were three times higher in women than men (p < 0.001). After adjustment for confounders, higher leptin levels were associated with lower LV mass (coefficient for 1 s.d. increase of leptin level: −5.825 g, 95% CI: −9.755 to −1.895 g, P = 0.004) and higher DWS (lower LV stiffness) (coefficient for 1 s.d. increase of leptin level: 0.009, 95% CI: 0.002–0.015, P = 0.007) in women. There were no statistically significant associations in men. In women, there were interactions between leptin levels and body mass index quartiles on LV mass and stiffness (p < 0.05 for both). Higher leptin levels were associated with lower LV mass and stiffness in obese but not lean black women.

Increased Proximal Aortic Diameter is Associated With Risk of Cardiovascular Events and All‐Cause Mortality in Blacks The Jackson Heart Study

Background Enlargement of the proximal aorta is associated with aortic wall tissue remodeling, including fragmentation of the elastin fibers, increased synthesis of collagen, and calcification, all of which are associated with aortic wall stiffening. We hypothesized that the proximal aortic diameter (AoD) is associated with cardiovascular events in a community‐based cohort of blacks. Methods and Results We investigated the associations between AoD and cardiovascular events among 3018 black participants (mean age, 55.9 years; 69% women) without past history of cardiovascular disease in the Jackson Heart Study. AoD was measured using echocardiography at the level of the sinuses of Valsalva at end diastole. Cardiovascular event was defined as incident myocardial infarction, fatal coronary artery disease, stroke, or heart failure hospitalization. Cox proportional hazards regression models were used to evaluate the association between baseline AoD and cardiovascular events. Over a median follow‐up of 8.3 years, there were 258 cardiovascular events (incident rate, 10.5 per 1000 person‐years). After adjustment for traditional risk factors, increased AoD was significantly associated with cardiovascular events (hazard ratio per 1‐cm increase, 1.72; 95% CI, 1.10–2.69; P<0.05). Participants in the top AoD quintile had a higher incidence of cardiovascular events compared to those not in the top quintile (hazard ratio, 1.47; 95% CI, 1.11–1.94; P<0.005) after adjustment for risk factors. Conclusions Greater AoD was associated with an increased risk of cardiovascular events in a community‐based cohort of blacks. AoD may be useful as a predictor of incident cardiovascular events and further investigation is warranted.

Elevated serum osteoprotegerin is associated with increased left ventricular mass index and myocardial stiffness

Aim Osteoprotegerin (OPG) is associated with a poor prognosis in patients with heart failure with preserved ejection fraction (HFpEF). OPG has also been associated with fibrosis and collagen cross-linking, which increase arterial and left ventricle (LV) myocardial stiffness. Little is known about the relation of OPG and LV structure and function in African-Americans who are disproportionately affected by HFpEF. Methods and results Our analysis included 1172 participants with preserved LV ejection fraction (>50%) from the African-American cohort in the Genetic Epidemiology Network of Arteriopathy Study (mean age 63 years, 72% female). We used diastolic wall strain indicator measured by echocardiography to assess LV myocardial stiffness. Diastolic wall strain was calculated as (LV posterior thickness at end-systole − LV posterior thickness at end-diastole)/LV posterior thickness at end-systole. Associations between OPG levels and indices of arterial and LV structure and function were evaluated by using generalized linear mixed models and adjusted for possible confounders. OPG levels were correlated with age, female sex, presence of hypertension and diabetes, and lower estimated glomerular filtration rate (P < 0.05 for all). Multivariable analysis revealed that higher OPG levels were associated with greater LV mass index, increased LV myocardial stiffness, and higher N-terminal prohormone brain natriuretic peptide levels (P < 0.05 for all). Conclusion In African-Americans, higher OPG levels were associated with characteristics common in patients with HFpEF and were significantly associated with known precursors to HFpEF. These findings indicate a potential role for OPG in the pathophysiology of HFpEF in African-Americans.

Diastolic wall strain is associated with incident heart failure in African Americans: Insights from the atherosclerosis risk in communities study

BACKGROUND Increased left ventricular (LV) myocardial stiffness may be associated with impaired LV hemodynamics and incident heart failure (HF). However, an indicator that estimates LV myocardial stiffness easily and non-invasively is lacking. The purpose of this study was to determine whether diastolic wall strain (DWS), an echocardiographic estimator of LV myocardial stiffness, is associated with incident HF in a middle-aged community-based cohort of African Americans. METHODS AND RESULTS We investigated associations between DWS and incident HF among 1528 African Americans (mean age 58.5 years, 66% women) with preserved LV ejection fraction (EF ≥50%) and without a history of cardiovascular disease in the Atherosclerosis Risk in Communities Study. Participants with the smallest DWS quintile (more LV myocardial stiffness) had a higher LV mass index, higher relative wall thickness, and lower arterial compliance than those in the larger four DWS quintiles (p<0.01 for all). Over a mean follow-up of 15.6 years, there were 251 incident HF events (incidence rate: 10.9 per 1000 person-years). After adjustment for traditional risk factors and incident coronary artery disease, both continuous and categorical DWS were independently associated with incident HF (HR 1.21, 95%CI 1.04-1.41 for 0.1 decrease in continuous DWS, p=0.014, HR 1.40, 95%CI 1.05-1.87 for the smallest DWS quintile vs other combined quintiles, p=0.022). CONCLUSIONS DWS was independently associated with an increased risk of incident HF in a community-based cohort of African Americans. DWS could be used as a qualitative estimator of LV myocardial stiffness.

Increased Left Ventricular Diastolic Stiffness Is Associated With Heart Failure Symptoms in Aortic Stenosis Patients With Preserved Ejection Fraction

BACKGROUND Clinical risk factors associated with heart failure (HF) symptoms in aortic stenosis (AS) patients with preserved ejection fraction (EF) have not been fully identified. We hypothesized that left ventricular (LV) diastolic stiffness is associated with HF symptoms in patients with AS. METHODS AND RESULTS We retrospectively evaluated 275 patients with at least moderate AS (aortic valve area <1.5 cm2) and preserved EF (≥50%). LV diastolic stiffness was evaluated with the use of echocardiographic parameters, diastolic wall strain (DWS, a measure of LV wall stiffness), and KLV (a marker of LV chamber stiffness). There were 69 patients with HF. Patients with HF were older, were more likely to be African American, had a higher body mass index, and had more hypertension and coronary artery disease (P < .05 for all). Aortic valve area index and mean pressure gradient across the aortic valve were not different between patients with and without HF. Despite similar echocardiographic parameters of AS severity, patients with HF had stiffer LV (DWS 0.21 ± 0.06 vs 0.25 ± 0.06 [P < .01], KLV 0.17 ± 0.11 vs 0.13 ± 0.08 [P < .01]). Logistic regression analyses revealed that after adjusting for age, race, body mass index, history of hypertension, and coronary artery disease, LV diastolic stiffness parameters remained significantly associated with HF symptoms. CONCLUSIONS LV diastolic stiffness is independently associated with HF in AS patients with preserved EF.

Arrhythmia in Bone Marrow Transplant Unit

A 35-year-old woman with a history of hypertension and chronic lymphocytic leukemia who underwent allogenic bone marrow transplant approximately 9 months prior presented to the emergency department with concern of shortness of breath and productive cough for a week. Her bone marrow transplant had been complicated with severe graftversus-host disease (GVHD) of skin and liver, diagnosed by biopsies 1 month after her transplant. In the emergency department, chest radiography showed multifocal airspace consolidations involving both lungs. Because of respiratory distress, she was admitted to the intensive care unit. She was subsequently diagnosed as having methicillin-resistant Staphylococcus aureus pneumonia. Respiratory failure developed, and the patient was intubated and treated with vasopressors. After 3 days in the intensive care unit, vasopressors were weaned off, and she was extubated. On hospital day 5, she was noted to have generalized erythematous skin with mild elevated liver enzyme, suggesting acute flare of chronic GVHD. Skin biopsy confirmed the diagnosis. Her hospital course was complicated with diffuse alveolar hemorrhage, possibly from pulmonary GVHD. Steroid and immunosuppressive medication doses were increased, and pulse methylprednisolone was started. At 48 hours after her skin lesions flared up, a change in her rhythm was noted on telemetry: her baseline sinus rhythm with heart rate of 90 beats per minute (bpm) was changed to bradycardia. A 12-lead electrocardiogram (ECG) is shown in the Figure. Her baseline ECG obtained a day earlier showed normal sinus rhythm with first-degree atrioventricular (AV) block (PR interval of 240 milliseconds). The patient denied symptoms associated with bradycardia. aVR