Objectives. This study was conducted to determine the utility of aortic valve resistance in assessing the severity of aortic stenosis.
Background. Assessment of the severity of aortic stenosis has ...traditionally employed hemodynamic data and the Gorlin formula to calculate the area of the aortic valve. Recently, flow dependence of the Gorlin formula has been identified and the accuracy of the formula challenged. Aortic valve resistance, the quotient of gradient and cardiac output, has been advanced as potentially useful in assessing the severity of valve stenosis.
Methods. We studied 48 symptomatic patients with an initial diagnosis of severe aortic stenosis based on a calculated aortic valve area of ≤0.8 cm2by the Gorlin formula. Forty of these patients (Group I) were confirmed to have severe stenosis, whereas 8 (Group II) were subsequently proved no severe aortic stenosis. The 18 patients in Group I with a severe area of 0.6 to 0.8 cm2(Group IA) were directly compared with Group II patients who had a similar valve area.
Results. Aortic valve area was nearly identical in Group IA and Group II patients (0.69 ± 0,05 and 0.71 ± 0.06 cm2, respectively, p = NS). However, aortic valve resistance was much less in Group II patients (212 ± 6 vs. 316 ± 11 dynes· s· cm−5, p < 0.0001). In this small cohort, aortic valve resistance achieved nearly complete separation of patients in Groups IA and II.
Conclusions. In some patients with relatively mild aortic stenosis, the calculated valve area may indicate that the stenosis is severe. The use of aortic valve resistance in conjanction with the Gorlin formula helps separate patients with truly severe aortic stenosis from those with milder disease.
Chronic supraventricular tachycardia (SVT) causes left ventricular (LV) dilatation and dysfunction. Changes in myocyte function and structure may be important factors in the development of SVT ...cardiomyopathy. Accordingly, LV function and isolated myocyte structure and function were examined in six pigs with pacing-induced SVT cardiomyopathy (3 weeks at 240 beats per minute) and six control pigs. LV function was examined by simultaneous echocardiography and catheterization, and isolated myocyte function was studied using computer-assisted video microscopy. Indexes of isolated myocyte contractile performance were examined in the unloaded, unattached state (31 control and 24 SVT cells) and after attachment to a basement membrane substrate (65 control and 45 SVT cells). LV fractional shortening and peak +dP/dt significantly decreased in SVT cells compared with control cells (12±2% versus 28±2%, and 842±61 versus 1,216±119 mm Hg/sec, respectively; p<0.05). Isolated myocyte percent shortening and normalized peak velocity of shortening of SVT myocytes adherent to a basement membrane were significantly lower than attached control myocytes (1.2±0.2% versus 4.3±0.3%, and 15±2 versus 37±5% resting cell length/sec, respectively; p<0.05). Similarly, in the unattached state, the extent and velocity of shortening of SVT myocytes were reduced by over 50% from control values. Contractile properties of attached and unattached cardiocytes were also examined in the presence of 2–8 mM extracellular Ca. For both attached and unattached SVT myocytes, responsiveness to increases in extracellular Ca were significantly blunted from control values. Ultrastructural examination of SVT myocytes revealed that the percent volume of myofibrils within isolated myocytes was reduced from control values (46±7% versus 65±2%, p<0.05). In summary, SVT cardiomyopathy is probably due to a primary defect in isolated myocyte contractile performance. The reduced contractile function of SVT cardiomyopathic myocytes was associated with abnormalities in cytoarchitecture and Ca responsiveness.
This study examined the relationship between income inequality and heart failure outcomes.
The income inequality hypothesis postulates that population health is influenced by income distribution ...within a society, with greater inequality associated with worse outcomes.
This study analyzed heart failure outcomes in 2 large trials conducted in 54 countries. Countries were divided by tertiles of Gini coefficients (where 0% represented absolute income equality and 100% represented absolute income inequality), and heart failure outcomes were adjusted for standard prognostic variables, country per capita income, education index, hospital bed density, and health worker density.
Of the 15,126 patients studied, 5,320 patients lived in Gini coefficient tertile 1 countries (coefficient: <33%), 6,124 patients lived in tertile 2 countries (33% to 41%), and 3,772 patients lived in tertile 3 countries (>41%). Patients in tertile 3 were younger than tertile 1 patients, were more often women, and had less comorbidity and several indicators of less severe heart failure, yet the tertile 3-to-1 hazard ratios (HRs) for the primary composite outcome of cardiovascular death or heart failure hospitalization were 1.57 (95% confidence interval CI: 1.38 to 1.79) and 1.48 for all-cause death (95% CI: 1.29 to 1.71) after adjustment for recognized prognostic variables. After additional adjustments were made for per capita income, education index, hospital bed density, and health worker density, these HRs were 1.46 (95% CI: 1.25 to 1.70) and 1.30 (95% CI: 1.10 to 1.53), respectively.
Greater income inequality was associated with worse heart failure outcomes, with an impact similar to those of major comorbidities. Better understanding of the societal and personal bases of these findings may suggest approaches to improve heart failure outcomes.
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Diabetic cardiomyopathy (DbCM), which consists of cardiac hypertrophy and failure in the absence of traditional risk factors, is a major contributor to increased heart failure risk in type 2 diabetes ...patients. In rodent models of DbCM, cardiac hypertrophy and dysfunction have been shown to depend upon saturated fatty acid (SFA) oversupply and de novo sphingolipid synthesis. However, it is not known whether these effects are mediated by bulk SFAs and sphingolipids or by individual lipid species. In this report, we demonstrate that a diet high in SFA induced cardiac hypertrophy, left ventricular systolic and diastolic dysfunction, and autophagy in mice. Furthermore, treatment with the SFA myristate, but not palmitate, induced hypertrophy and autophagy in adult primary cardiomyocytes. De novo sphingolipid synthesis was required for induction of all pathological features observed both in vitro and in vivo, and autophagy was required for induction of hypertrophy in vitro. Finally, we implicated a specific ceramide N-acyl chain length in this process and demon-strated a requirement for (dihydro)ceramide synthase 5 in cardiomyocyte autophagy and myristate-mediated hypertrophy. Thus, this report reveals a requirement for a specific sphingolipid metabolic route and dietary SFAs in the molecular pathogenesis of lipotoxic cardiomyopathy and hypertrophy.
1 Cardiology Section of the
Department of Medicine and the Department of Physiology, Gazes
Cardiac Research Institute, Medical University of South Carolina and
the Veterans Affairs Medical Center, ...Charleston, South Carolina
29401; 2 Veterans Affairs Medical
Center, Boston, Massachusetts 02130;
3 Department of Anatomy and Cell
Biology, University of Iowa College of Medicine, Iowa City, Iowa 52242;
and 4 Department of Medicine,
University of Alabama at Birmingham, Birmingham, Alabama
35294
Myocardial
hypertrophy is one of the basic mechanisms by which the heart
compensates for hemodynamic overload. The mechanisms by which
hemodynamic overload is transduced by the cardiac muscle cell and
translated into cardiac hypertrophy are not completely understood.
Candidates include activation of the renin-angiotensin system (RAS) and
angiotensin II receptor (AT 1 )
stimulation. In this study, we tested the hypothesis that load,
independent of the RAS, is sufficient to stimulate cardiac growth. Four
groups of cats were studied: 14 normal controls, 20 pulmonary
artery-banded (PAB) cats, 7 PAB cats in whom the
AT 1 was concomitantly and
continuously blocked with losartan, and 8 PAB cats in whom the
angiotensin-converting enzyme (ACE) was concomitantly and continuously
blocked with captopril. Losartan cats had at least a one-log order
increase in the ED 50 of the blood
pressure response to angiotensin II infusion. Right ventricular (RV)
hypertrophy was assessed using the RV mass-to-body weight ratio and
ventricular cardiocyte size. RV hemodynamic overload was assessed by
measuring RV systolic and diastolic pressures. Neither the extent of RV
pressure overload nor RV hypertrophy that resulted from PAB was
affected by AT 1 blockade with
losartan or ACE inhibition with captopril. RV systolic pressure was
increased from 21 ± 3 mmHg in normals to 68 ± 4 mmHg in PAB, 65 ± 5 mmHg in PAB plus losartan and 62 ± 3 mmHg in PAB plus
captopril. RV-to-body weight ratio increased from 0.52 ± 0.04 g/kg
in normals to 1.11 ± 0.06 g/kg in PAB, 1.06 ± 0.06 g/kg in PAB
plus losartan and 1.06 ± 0.06 g/kg in PAB plus captopril. Thus
1 ) pharmacological modulation of the
RAS with losartan and captopril did not change the extent of the
hemodynamic overload or the hypertrophic response induced by PAB;
2 ) neither RAS activation nor
angiotensin II receptor stimulation is an obligatory and necessary
component of the signaling pathway that acts as an intermediary
coupling load to the hypertrophic response; and
3 ) load, independent of the RAS, is
capable of stimulating cardiac growth.
myocardial hypertrophy; angiotensin II; pulmonary artery
band
The burden of heart failure with preserved ejection fraction (HFpEF) is considerable and is projected to worsen. To date, there are no approved therapies available for reducing mortality or ...hospitalizations for these patients. The pathophysiology of HFpEF is complex and includes alterations in cardiac structure and function, systemic and pulmonary vascular abnormalities, end-organ involvement, and comorbidities. There remain major gaps in our understanding of HFpEF pathophysiology. To facilitate a discussion of how to proceed effectively in future with development of therapies for HFpEF, a meeting was facilitated by the Food and Drug Administration and included representatives from academia, industry, and regulatory agencies. This document summarizes the proceedings from this meeting.
This study sought to describe baseline health-related quality of life (HRQL) in the PARAGON-HF (Prospective Comparison of ARNI with ARB Global Outcomes in HFpEF) trial, the largest heart failure with ...preserved ejection fraction (HFpEF) trial to date.
There are limited data characterizing HRQL in patients with HFpEF using validated metrics.
The PARAGON-HF trial randomized symptomatic patients with HFpEF (≥45%) ≥50 years of age to either sacubitril/valsartan or valsartan. The study reports comprehensive baseline HRQL using Kansas City Cardiomyopathy Questionnaire (KCCQ) administered at randomization after active run-in period. The study then compares baseline HRQL with patients with heart failure with reduced ejection fraction (HFrEF) (≤40%) enrolled in the PARADIGM-HF (Prospective Comparison of ARNI with an ACE-Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure) trial. Forward multivariable stepwise regression modeling was performed separately in both trials to identify independent clinical correlates of KCCQ-Overall Summary (KCCQ-OS) score. PARADIGM-HF trial patients <50 years of age were excluded to enable comparison.
In the PARAGON-HF trial, 4,735 of 4,822 patients (mean age 73 ± 8 years; 48% men) completed baseline KCCQ at randomization. Mean KCCQ-OS score was 71. Women had worse mean KCCQ-OS score than men did. Patients in the PARAGON-HF trial reported lower KCCQ scores in nearly all domains when compared with the PARADIGM-HF trial (KCCQ-OS score 71 ± 19 vs. 73 ± 19; p < 0.001). The strongest independent clinical correlates of adverse HRQL in both the PARAGON-HF and PARADIGM-HF trials were New York Heart Association functional class, female gender, lower extremity edema, body mass index, angina, dyspnea, and paroxysmal nocturnal dyspnea. After accounting for these clinical correlates of adverse HRQL that were common to both HFpEF and HFrEF patients, KCCQ-OS score did not differ significantly.
HRQL was largely worse in women and was similar in HFpEF and HFrEF after accounting for variation in demographics, functional status, and symptom burden. (Prospective Comparison of ARNI with ARB Global Outcomes in HFpEF PARAGON-HF NCT01920711; Prospective Comparison of ARNI with an ACE-Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure PARADIGM-HF; NCT01035255)
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Reply Shah, Amil M; Kraigher-Krainer, Elisabeth; Gupta, Deepak K ...
Journal of the American College of Cardiology,
10/2014, Letnik:
64, Številka:
14
Journal Article
Recenzirano
Furthermore, to better understand how subtle abnormalities in systolic function, identified by these deformation measures, affects the clinical status of patients with HFpEF, future studies will also ...need to characterize the physiological and hemodynamic implications of impaired strain.
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