Mathew S. Maurer

Comparison of Ventricular Structure and Function in Chinese Patients With Heart Failure and Ejection Fractions >55% Versus 40% to 55% Versus <40%

Subjects with heart failure (HF) and a preserved ejection fraction (EF) are heterogenous and the EF used to define this syndrome varies considerably among studies. We sought to determine if physiologic differences exist between subjects with a normal EF (>55%) or mildly decreased EF (40% to 55%). 357 consecutive Chinese patients who were healthy (n = 93) or had HF (n = 264) underwent comprehensive echocardiography, Doppler analysis, and measurement of neurohormones. Subjects with HF were stratified by EF into those with normal EF (>55%, n = 128), mildly decreased EF (40% to 55%, n = 38), or moderate to severely decreased EF (<40%, n = 100). Employing noninvasive pressure-volume analysis, estimated end-systolic and end-diastolic pressure-volume relations were calculated. Subjects with HF and an EF 40% to 55% more often had a previous myocardial infarction and diabetes than those with HF and an EF >55%. Physiologically, the cohort with a mildly decreased EF had eccentrically enlarged ventricles with evidence of remodeling (rightward shifted end-diastolic pressure-volume relation) and decreased chamber contractility (downward shifted end-systolic pressure-volume relation) most comparable to subjects with overt systolic HF. In conclusion, in subjects with HF and a preserved EF, there are distinct physiologic differences between those with a normal (>55%) and a mildly decreased (40% to 55%) EF.

The Impact of Extra Cardiac Comorbidities on Pressure Volume Relations in Heart Failure and Preserved Ejection Fraction

BACKGROUNDnExtracardiac comorbidities are common in patients with heart failure and a preserved ejection fraction (HFPEF). We sought to evaluate the relationship between comorbidities and ventricular structure and function in patients with HFPEF through evaluation of pressure-volume analysis.nnnMETHODS AND RESULTSnTwo hundred twenty Chinese patients with a preserved ejection fraction who were either healthy (nxa0= 75), hypertensive without heart failure (HTN; nxa0= 89), or hypertensive with HFPEF (HFPEF; nxa0= 56) were studied. Using echocardiographic measures, estimated end-systolic and end-diastolic pressure-volume relationships, and the area between them as a function of EDP, the isovolumic pressure-volume areas (PVA(iso)), were calculated. Ventricular capacitance, as measured by V(30), was larger in patients with HFPEF compared with normal control subjects and tended to be larger compared with hypertensive control subjects. The presence of diabetes and renal insufficiency was independently associated with greater ventricular capacitance in patients with HFPEF. The PVA(iso) was increased in patients with HFPEF compared with HTN and normal control subjects, and in particular, it was increased in HFPEF patients with multiple comorbidities.nnnCONCLUSIONSnThe presence of comorbid conditions is associated with altered pressure-volume relations and enhanced pump function in subjects with HFPEF, supporting an important role for extracardiac comorbidities in the pathophysiology of patients with this condition.

Ventriculovascular coupling in systolic and diastolic heart failure.

Pressure-volume analysis has provided critical insight into ventricular mechanics, and it has elucidated the underlying mechanisms of heart failure (HF). Renewed interest in ventriculovascular coupling, the interaction of the left ventricle and the arterial system, has developed from recent investigations focusing on the importance of heart rate control in systolic HF, blood pressure lability in the elderly, and acute pulmonary edema in patients with HF and a normal ejection fraction. These data suggest that abnormal ventriculovascular coupling may be an additional pathophysiologic mechanism underlying the development of HF with a normal ejection fraction and may provide a target for novel therapies.

Salt Taste Recognition in a Heart Failure Cohort

BACKGROUNDnHeart failure (HF) disproportionately affects older adults. Dietary sodium indiscretion is frequently implicated in HF decompensation. The affinity for and ability to taste salt in this process is unexplored. We sought to evaluate differences in salt taste by age and HF diagnosis and to map changes after hospitalization for acute decompensated heart failure (ADHF).nnnMETHODSnSeventy-two subjects underwent initial salt-taste testing during hospitalization for ADHF. Follow-up taste testing occurred at discharge and 1, 4, and 12 weeks after hospitalization. Three different groups were included as control subjects and underwent 1-time salt-taste testing: 10 patients with stable HF, 10 healthy older adults, and 10 healthy younger adults. Salt-taste testing was completed with the use of commercially available and validated Salsave test strips with increasing concentrations of NaCl (0.6-1.6u2009mg/cm2) to identify salt taste recognition threshold. Respectively, 2-sample t tests, multiple regression, and linear mixed-effects modeling were used for intergroup comparisons, to adjust for confounders, and to assess the effect of time after discharge from ADHF hospitalization.nnnRESULTSnThe baseline salt taste recognition threshold was lowest in the young healthy control group (0.62 [SD 0.05] mg/cm2 NaCl) compared with the healthy older control subjects (0.92 [SD 0.29] mg/cm2 NaCl), stable HF outpatients, (1.06 [SD 0.22] mg/cm2 NaCl), and ADHF subjects on admission (1.06 [SD 0.48] mg/cm2 NaCl). There was a strong trend toward higher recognition threshold in HF patients (Pu2009=u2009.051) that was independent from age and other potential confounders. Serial salt-taste testing in the ADHF group demonstrated a decrease in recognition threshold that persisted over the 12 weeks after discharge (1.04 [SD 0.44] to 0.76 [SD 0.22] mg/cm2 NaCl; Pu2009=u2009.003).nnnDISCUSSIONnWhen compared with young healthy control subjects, HF patients have impaired recognition of salt taste. The salt taste recognition threshold decreases after hospitalization for ADHF. This change demonstrates the first evidence of the phenomenon known as the hedonic shift in HF, in which the threshold to recognize salt taste decreases after prescribed sodium restriction.

Estimating cancer risk from 99mTc pyrophosphate imaging for transthyretin cardiac amyloidosis

BackgroundIncreasing recognition that transthyretin cardiac amyloidosis (ATTR-CA) is much more common than previously appreciated and the emergence of novel disease-modifying therapeutic agents have led to a paradigm shift in which ATTR-CA screening is considered in high-risk populations, such as patients with heart failure with preserved ejection fraction (HFpEF) or aortic stenosis. Radiation risk from 99mTc-pyrophosphate (99mTc-PYP) scintigraphy, a test with very high sensitivity and specificity for ATTR-CA, has not been previously determined.Methods and ResultsRadiation doses to individual organs from 99mTc-PYP were estimated using models developed by the Medical Internal Radiation Dose Committee and the International Commission on Radiological Protection. Excess future cancer risks were estimated from organ doses, using risk projection models developed by the National Academies and extended by the National Cancer Institute. Excess future risks were estimated for men and women aged 40-80 and compared to total (excess plus baseline) future risks. All-organ excess cancer risks (90% uncertainty intervals) ranged from 5.88 (2.45,11.4) to 12.2 (4.11,26.0) cases per 100,000 patients undergoing 99mTc-PYP testing, were similar for men and women, and decreased with increasing age at testing. Cancer risks were highest to the urinary bladder, and bladder risk varied nearly twofold depending on which model was used. Excess 99mTc-PYP-related cancers constitutedu2009<u20091% of total future cancers to the critical organs.ConclusionVery low cancer risks associated with 99mTc-PYP testing suggest a favorable benefit-risk profile for 99mTc-PYP as a screening test for ATTR-CA in high-risk populations, such as such as patients with HFpEF or aortic stenosis.