Noninvasive cardiac output estimation by inert gas rebreathing in pediatric and congenital heart disease.

BACKGROUND: Inert gas rebreathing (IGR) techniques provide rapid, reliable estimates of cardiac output in adults with structurally normal hearts. Data on IGR reliability in pediatric and congenital heart disease populations are lacking. Our objective was to validate pulmonary blood flow (Qp) measurement by IGR compared with clinical reference tests, cardiovascular magnetic resonance (CMR), and indirect Fick. METHODS: Pulmonary blood flow was measured by IGR and CMR or indirect Fick in 80 patients grouped by presence and type of shunt lesion. Inert gas rebreathing precision was assessed using Bland-Altman analysis, repeatability coefficient, intraclass correlation, and coefficient of error. Agreement with the reference tests was assessed with Bland-Altman plots. For comparison, agreement between the 2 reference tests, CMR and indirect Fick, was assessed in 34 contemporary patients. RESULTS: Subjects were aged 7-78 years and had a wide range of cardiac diagnoses. Inert gas rebreathing Qp showed good repeatability (95% limits of agreement for 2 trials = ±22%, repeatability coefficient = 1.2 L/min, intraclass correlation = 0.92, and coefficient of error = 5%). In the absence of left-to-right shunting (n = 67), IGR Qp estimates agreed with CMR and indirect Fick Qp estimates, and the reference tests agreed with each other, with mean bias ≤10% (≤0.5 L/min) and 95% limits of agreement ±33%-38%. Conversely, IGR was unreliable in patients with left-to-right shunt (n = 14), with large bias (-58%, -4.0 L/min) and wide limits of agreement (±76%). CONCLUSIONS: Inert gas rebreathing reliably estimates Qp in children and adults with congenital heart disease in the absence of left-to-right shunting, with agreement comparable to that seen between CMR and indirect Fick estimates.

Distribution of 10-year and lifetime predicted risks for cardiovascular disease in US adults: findings from the National Health and Nutrition Examination Survey 2003 to 2006.

BACKGROUND: National guidelines for primary prevention suggest consideration of lifetime risk for cardiovascular disease in addition to 10-year risk, but it is currently unknown how many US adults would be identified as having low short-term but high lifetime predicted risk if stepwise stratification were used. METHODS AND RESULTS: We included 6329 cardiovascular disease-free and nonpregnant individuals ages 20 to 79 years, representing approximately 156 million US adults, from the National Health and Nutrition Examination Survey 2003 to 2004 and 2005 to 2006. We assigned 10-year and lifetime predicted risks to stratify participants into 3 groups: low 10-year (<10%)/low lifetime (<39%) predicted risk, low 10-year (<10%)/high lifetime (> or = 39%) predicted risk, and high 10-year (> or = 10%) predicted risk or diagnosed diabetes. The majority of US adults (56%, or 87 million individuals) are at low short-term but high lifetime predicted risk for cardiovascular disease. Twenty-six percent (41 million adults) are at low short-term and low lifetime predicted risk, and only 18% (28 million individuals) are at high short-term predicted risk. The addition of lifetime risk estimation to 10-year risk estimation identifies higher-risk women and younger men in particular. CONCLUSIONS: Whereas 82% of US adults are at low short-term risk, two thirds of this group, or 87 million people, are at high lifetime predicted risk for cardiovascular disease. These results provide support for use of a stepwise stratification system aimed at improving risk communication, and they provide a baseline for public health efforts aimed at increasing the proportion of Americans with low short-term and low lifetime risk for cardiovascular disease.

Systematic examination of the updated Framingham heart study general cardiovascular risk profile.

BACKGROUND: An updated Framingham risk prediction tool was recently published. It features an expanded end point of general cardiovascular disease and a "vascular age" risk communication analogy. METHODS AND RESULTS: We systematically examined the tool to determine which risk factor combinations allow risk thresholds to be reached and how different risk factor burdens translate into vascular age. We varied risk factor levels in isolation and combination and observed risk output patterns, with high risk defined as > or =20% 10-year predicted risk. As expected, we found that age is the major determinant of 10-year predicted risk for both men and women. Younger individuals tend not to exceed 20% 10-year risk even with multiple risk factors, although with marked risk factor burden, including both smoking and diabetes mellitus, men as young as 35 years of age and women as young as 40 years of age can be classified as high risk. For the risk factor levels we entered, predicted risk ranges from 3.1% to 46.8% for a 45-year-old man and 2.4% to 42.7% for a 55-year-old woman. Likewise, vascular age ranges from 37 to >80 years for a 45-year-old man and 39 to >80 years for a 55-year-old woman. CONCLUSIONS: The inclusion of noncoronary end points in this tool expands the range of predicted risks for men and women at all ages studied. Nevertheless, many younger individuals with high risk factor burden have low 10-year predicted risk. Wide ranges of "vascular age" are available for most chronological ages to assist with risk communication.

Differential susceptibility of midbrain and spinal cord patterning to floor plate defects in the talpid2 mutant.

The chick talpid2 mutant displays polydactylous digits attributed to defects of the Hedgehog (HH) signaling pathway. We examined the talpid2 neural tube and show that patterning defects in the spinal cord and the midbrain are distinct from each other and from the limb. Unlike the Sonic Hedgehog (SHH) source in the limb, the SHH-rich floor plate (FP) is reduced in the talpid2 midbrain. This is accompanied by a severe depletion of medial cell populations that encounter high concentrations of SHH, an expansion of lateral cell populations that experience low concentrations of SHH and a broad deregulation of HH's principal effectors (PTC1, GLI1, GLI2, GLI3). Together with the failure of SHH misexpression to rescue the talpid2 phenotype, these results suggest that talpid2 is likely to have a tissue-autonomous, bidirectional (positive and negative) role in HH signaling that cannot be attributed to the altered expression of several newly cloned HH pathway genes (SUFU, DZIP1, DISP1, BTRC). Strikingly, FP defects in the spinal cord are accompanied by relatively normal patterning in the talpid2 mutant. We propose that this differential FP dependence may be due to the prolonged apposition of the notochord to the spinal cord, but not the midbrain during development.