Gilbert J. Perry

Evaluation of aortic insufficiency by Doppler color flow mapping

The color Doppler echocardiographic studies and aortic angiograms of all patients who had these procedures performed within 2 weeks of each other between October 1984 and August 1985 were reviewed to determine whether any parameters of the regurgitant jet visualized by color Doppler study predicted the severity of aortic insufficiency as assessed by angiographic grading. Patients with an aortic valve prosthesis were excluded. Twenty-nine patients had aortic insufficiency and had adequate color Doppler studies for analysis. The mean time between color Doppler examination and angiography was 2.3 days (range 0 to 12). The maximal length and area of the regurgitant jet were poorly predictive of the angiographic grade of aortic insufficiency. The short-axis area of the regurgitant jet from the parasternal short-axis view at the level of the high left ventricular outflow tract relative to the short-axis area of the left ventricular outflow tract at the same location best predicted angiographic grade, correctly classifying 23 of 24 patients. However, the jet could be seen from this view in only 24 of the 29 patients. The height of the regurgitant jet relative to left ventricular outflow tract height measured from the parasternal long-axis view just beneath the aortic valve correctly classified 23 of the 29 patients. Mitral stenosis or valve prosthesis, which was present in 10 patients, did not interfere with the diagnosis or quantitation of aortic insufficiency by these methods.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of Right Ventricular Ejection Fraction on Outcomes in Chronic Systolic Heart Failure

Background— Studies of the effect of right ventricular ejection fraction (RVEF) on outcomes in heart failure (HF) are limited by small sample size and short follow-up. Methods and Results— We examined the effect of baseline RVEF on outcomes in 2008 Beta-Blocker Evaluation of Survival Trial (BEST) participants with HF and left ventricular ejection fraction ≤35% during 24 months of mean follow-up. RVEF, estimated by gated-equilibrium radionuclide ventriculography, was used to categorize patients into 4 RVEF groups: ≥40% (n=733), 30% to 39% (n=531), 20% to 29% (n=473), and <20% (n=271). Unadjusted rates for all-cause mortality in patients with RVEF ≥40%, 30% to 39%, 20% to 29%, and <20% were 27%, 32%, 35%, and 47%, respectively. When compared with patients with RVEF ≥40%, unadjusted hazard ratios and 95% confidence intervals for all-cause mortality for those with RVEF 30% to 39%, 20% to 29%, and <20% were 1.19 (0.97 to 1.46; P=0.087), 1.45 (1.17 to 1.78; P=0.001), and 1.98 (1.59 to 2.47; P<0.0001), respectively. Respective multivariable-adjusted hazard ratios (95% confidence intervals) for all-cause mortality associated with RVEF 30% to 39%, 20% to 29%, and <20% were 1.07 (0.87 to 1.32; P=0.518), 1.12 (0.89 to 1.40; P=0.328), and 1.32 (1.02 to 1.71; P=0.034), respectively. Adjusted hazard ratios (95% confidence intervals) for other outcomes associated with RVEF <20% (compared with ≥40%) were as follows: cardiovascular mortality, 1.33 (1.01 to 1.76; P=0.041); HF mortality, 1.61 (1.03 to 2.52; P=0.037); sudden cardiac death, 1.29 (0.87 to 1.91; P=0.212); all-cause hospitalization, 1.21 (1.00 to 1.47; P=0.056); and HF hospitalization, 1.39 (1.10 to 1.77; P=0.007). Conclusions— Baseline RVEF <20% is a significant independent predictor of mortality and HF hospitalization in systolic HF.

The scope of coronary heart disease in patients with chronic kidney disease.

Chronic kidney disease (CKD) affects approximately 13% of the U.S. population and is associated with increased risk of cardiovascular complications. Once renal replacement therapy became available, it became apparent that the mode of death of patients with advanced CKD was more likely than not related to cardiovascular compromise. Further observation revealed that such compromise was related to myocardial disease (related to hypertension, stiff vessels, coronary heart disease, or uremic toxins). Early on, the excess of cardiovascular events was attributed to accelerated atherosclerosis, inadequate control of blood pressure, lipids, or inflammatory cytokines, or perhaps poor glycemia control. In more recent times, outcome research has given us further information that relates even lesser degrees of renal compromise to an excess of cardiovascular events in the general population and in those with already present atherosclerotic disease. As renal function deteriorates, certain physiologic changes occur (perhaps due to hemodynamic, inflammatory, or metabolic changes) that decrease oxygen-carrying capacity of the blood by virtue of anemia, make blood vessels stiffer by altering collagen or through medial calcinosis, raise the blood pressure, increase shearing stresses, or alter the constituents of atherosclerotic plaque or the balance of thrombogenesis and thrombolysis. At further levels of renal dysfunction, tangible metabolic perturbations are recognized as requiring specific therapy to reduce complications (such as for anemia and hyperparathyroidism), although outcome research to support some of our current guidelines is sorely lacking. Understanding the process by which renal dysfunction alters the prognosis of cardiac disease might lead to further methods of treatment. This review will outline the relationship of CKD to coronary heart disease with respect to the current understanding of the traditional and nontraditional risk factors, the role of various imaging modalities, and the impact of coronary revascularization on outcome.

Effects of Pressure Overload on Extracellular Matrix Expression in the Heart of the Atrial Natriuretic Peptide–Null Mouse

Abstract—This study tested the hypothesis that atrial natriuretic peptide has direct antihypertrophic actions on the heart by modulating expression of genes involved in cardiac hypertrophy and extracellular matrix production. Hearts of male, atrial natriuretic peptide–null and control wild-type mice that had been subjected to pressure overload after transverse aortic constriction and control unoperated hearts were weighed and subjected to microarray, Northern blot, and immunohistochemical analyses. Microarray and Northern blot analyses were used to identify genes that are regulated differentially in response to stress in the presence and absence of atrial natriuretic peptide. Immunohistochemical analysis was used to identify and localize expression of the protein products of these genes. Atrial natriuretic peptide–null mice demonstrated cardiac hypertrophy at baseline and an exaggerated hypertrophic response to transverse aortic constriction associated with increased expression of the extracellular matrix molecules periostin, osteopontin, collagen I and III, and thrombospondin, as well as the extracellular matrix regulatory proteins, matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase-3, and the novel growth factor pleiotrophin compared with wild-type controls. These results support the hypothesis that atrial natriuretic peptide protects against pressure overload–induced cardiac hypertrophy and remodeling by negative modulation of genes involved in extracellular matrix deposition.

Angiotensin II receptor blockade does not improve left ventricular function andremodeling in subacute mitral regurgitation in the dog

OBJECTIVES We hypothesized that angiotensin II type-1 (AT(1)) receptor blocker (AT(1)RB) would prevent adverse left ventricular (LV) remodeling and LV dysfunction when started at the outset of mitral regurgitation (MR). BACKGROUND Little is known regarding the efficacy of AT(1)RB treatment of MR. METHODS Mitral regurgitation was induced by chordal disruption in adult mongrel dogs. Six normal dogs (NLs) were compared to six untreated MR dogs (MR) and seven dogs treated with the receptor blocker irbesartan (MR+AT(1)RB) started 24 h after induction of MR (60 mg/kg p.o. b.i.d.) and continued for three months. RESULTS Treatment with AT(1)RB decreased systemic vascular resistance but did not significantly improve cardiac output, LV end-diastolic dimension (LVEDD) or LVEDD/wall thickness compared to untreated MR dogs. Resting isolated cardiomyocyte length increased in MR versus NLs and was further increased in AT(1)RB dogs. Left ventricular end-systolic dimension increased to a greater extent from baseline in AT(1)RB dogs versus untreated MR dogs (29 +/- 9% vs. 12 +/- 6%, p < 0.05), despite a significantly lower LV peak systolic pressure in AT(1)RB dogs. Plasma-angiotensin (ANG) II was elevated greater than threefold in both MR and MR+AT(1)RB versus NLs. In contrast, intracardiac ANG II was increased greater than twofold in MR dogs versus NLs, but was normalized by AT(1)RB. CONCLUSIONS The use of AT(1)RB decreased systemic vascular resistance and attenuated local expression of the renin-angiotensin system but did not prevent adverse LV chamber and cardiomyocyte remodeling. These results suggest that blockade of the AT(1) receptor does not improve LV remodeling and function in the early myocardial adaptive phase of MR.

Impact of Atrial Fibrillation on Mortality and Readmission in Older Adults Hospitalized with Heart Failure

Atrial fibrillation is common in older adults with heart failure. It is known to adversely affect outcomes.

Atrial Natriuretic Peptide Dose-Dependently Inhibits Pressure Overload-Induced Cardiac Remodeling

We hypothesized that a single copy of the proatrial natriuretic peptide gene (Nppa+/−) would not be adequate to protect heterozygous mice against exaggerated cardiac hypertrophy and remodeling after pressure-overload stress. Nppa+/+, Nppa+/−, and Nppa−/− mice were subjected to sham surgery or transverse aortic constriction and fed a basal salt diet. Heart weight varied inversely with Nppa gene load by 1 week after either surgery. Fractional shortening did not differ among genotypes at baseline and fell in Nppa−/− mice only after transverse aortic constriction. There was a graded response in collagen deposition related to atrial natriuretic peptide (ANP) expression after either surgery. A robust interstitial and perivascular fibrosis was noted in Nppa−/− and Nppa+/− but not in Nppa+/+ mice after transverse aortic constriction. Our findings are consistent with a growing body of evidence that ANP is an important modulator of cardiac hypertrophy and remodeling in response to hemodynamic stress. The observation that partial ANP deficiency results in exaggerated hypertrophy and remodeling after pressure overload suggests that genetic or environmental variation in ANP levels may play a role in the development of cardiac hypertrophy, remodeling, and failure in humans.

Pressure‐independent enhancement of cardiac hypertrophy in atrial natriuretic peptide–deficient mice

1. Homozygous deletion of the pro‐atrial natriuretic peptide (Nppa) gene (ANP–/–) has been associated with both cardiac hypertrophy and salt‐sensitive hypertension in mice, suggesting that cardiac hypertrophy in ANP–/– mice may be related, at least in part, to increased afterload.

Systolic Dysfunction Portends Increased Mortality among Those Waiting for Renal Transplant

Individuals waiting for a renal transplant experience excessive cardiovascular mortality, which is not fully explained by the prevalence of ischemic heart disease in this population. Overt heart failure is known to increase the mortality of patients with ESRD, but the impact of lesser degrees of ventricular systolic dysfunction is unknown. For examination of the association between left ventricular ejection fraction(LVEF) and mortality of renal transplant candidates, the records of 2718 patients evaluated for transplantation at one institution were reviewed. During 6355 patient-years (median 27 mo) of follow-up, 681 deaths occurred. Patients with systolic dysfunction (LVEF <or= 0.40) had significantly lower survival than those with higher systolic function (median 49 +/- 3.1 versus 72 +/- 4.0 mo; P 0.001) but had similar survival to patients with ischemia (48 +/- 2.5 mo). Multivariate modeling showed that those with systolic dysfunction were nearly twice as likely to die as those with normal systolic function, adjusted for risk factors including diabetes, left ventricular hypertrophy, and ischemia (adjusted hazard ratio 1.7; 95%confidence interval 1.43 to 2.07). In addition, a graded, reverse association between LVEF and mortality was identified. In conclusion, systolic dysfunction is strongly associated with mortality, in a graded manner, in renal transplant candidates.

Magnetic Resonance Imaging With 3-Dimensional Analysis of Left Ventricular Remodeling in Isolated Mitral Regurgitation Implications Beyond Dimensions

Background— Although surgery is indicated in patients with mitral regurgitation (MR) when left ventricular (LV) end-systolic (LVES) dimension is >40 mm, LV ejection fraction may decrease after mitral valve surgery. We hypothesize that significant LV remodeling before surgery is not reflected by standard echocardiographic parameters measured at the base of the heart. Methods and Results— Ninety-four patients (age, 54±11 years; 38% female) with degenerative isolated MR underwent cine magnetic resonance imaging with tissue tagging and 3-dimensional analysis. In 51 control subjects (age, 44±14 years; 53% female), the relation between LVES volume (LVESV) and LVES dimension was quadratic, whereas in 94 MR patients, this relation was cubic, indicating a greater increase in LVESV per LVES dimension among MR patients. Moreover, magnetic resonance imaging LVESV from summated serial short-axis slices was significantly greater than LVESV assessed with the Bullet formula in MR patients, attributed to a more spherical remodeling distal to the tips of the papillary muscles (P<0.001). Thirty-five patients underwent mitral valve repair per current guideline recommendations. LV ejection fraction decreased from 61±7% to 54±8% (P<0.0001) and maximum shortening decreased significantly below normal at 1 year postoperatively (P<0.0001). Despite normalization of LV stroke volume and LV end-diastolic volume/mass ratio, there was a persistent significant increase in distal LVES 3-dimensional radius/wall thickness ratio and LVESV index after surgery. Conclusions— Despite apparently preserved LVES dimension, MR patients demonstrate significant spherical mid to apical LVES remodeling that contributes to higher LVESV than predicted by standard geometry-based calculations. Decreased LV strain after surgery suggests that a volumetric analysis of LV remodeling and function may be preferred to evaluate disease progression in isolated MR.