Inducible nitric oxide synthase in severe human heart failure: impact of mechanical unloading.
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Heart Failure↗
Biomedical subjects
Randall C Starling
Publications and source records attributed to Randall C Starling.
Multicenter intravascular ultrasound validation study among heart transplant recipients: outcomes after five years.
OBJECTIVES: We sought to assess the validity of first-year intravascular ultrasound (IVUS) data as a surrogate marker for long-term outcome after heart transplantation. BACKGROUND: Cardiac allograft vasculopathy (CAV) is a major impediment to long-term graft survival. Intravascular ultrasound is more sensitive than coronary angiography and detects intimal thickening (early CAV) in the coronary arteries of the donor heart. Single-center studies have suggested first-year IVUS results might be a surrogate marker for long-term outcome. METHODS: First-year IVUS results and subsequent five-year clinical follow-up data were reviewed in 125 heart transplant recipients from five institutions. The IVUS tapes (at baseline and one year) were re-analyzed at a core IVUS laboratory. The change in maximal intimal thickness (MIT) from baseline to one year was recorded for several matched sites in the same coronary artery. Patients were classified into two groups: those with >/=0.5 mm in the MIT in any matched site (group 1) and those with MIT <0.5 mm (group 2). RESULTS: Group 1 patients compared with group 2 patients had a higher incidence of death or graft loss (D/GL, 20.8% vs. 5.9%; p = 0.007), had more nonfatal major adverse cardiac events and/or D/GL (45.8% vs. 16.8%; p = 0.003), and had more findings of newly occurring angiographic luminal irregularities (65.2% vs. 32.6%, p = 0.004). CONCLUSIONS: This multicenter study suggests that progression of intimal thickening >/=0.5 mm in the first year after transplantation appears to be a reliable surrogate marker for subsequent mortality, nonfatal major adverse cardiac events, and development of angiographic CAV through five years after heart transplantation.
Adult↗
Bench repair of donor aortic valve with minimal access orthotopic heart transplantation.
While the number of people waiting heart transplantation increases, the number of organ donors decreases. This shrinking donor pool has prompted reassessment of donor selection for heart transplantation. Bench repair of a donor aortic valve was performed before minimal access orthotopic heart transplantation. Aortic insufficiency in the structurally normal tricuspid aortic valve was due to annular dilatation and was corrected with subcommissural annular plication. The postoperative period was uneventful. Follow-up at 4.5 years showed good results and no evidence of aortic regurgitation.
Aortic Valve↗
Minimally invasive left ventricular epicardial lead placement: surgical techniques for heart failure resynchronization therapy.
BACKGROUND: Epicardial lead placement for biventricular pacing is often a rescue procedure after failed coronary sinus cannulation. This study aims to determine perioperative and early postoperative outcome of minimally invasive left ventricular lead placement as a management strategy for heart failure, comparing minithoracotomy and endoscopic approaches. METHODS: From October 2002 through October 2003, 41 patients underwent minimally invasive left ventricular lead placement, 23 (56%) by minithoracotomy and 18 (44%) endoscopically. Thirty-one (76%) were males, 19 (46%) had previous cardiac surgery, 21 (51%) had ischemic cardiomyopathy, 17 (41%) were in New York Heart Association class III or IV, and 28 (65%) had implantable cardioverter-defibrillators. RESULTS: There were no in-hospital deaths, intraoperative complications, or failures to implant the left ventricular lead. Median operative time was longer for the endoscopic approach (188 minutes) than for minithoracotomy (151 minutes; p = 0.006). Preoperatively, the endoscopic group had more mitral regurgitation (median, 2.5 versus 1.0, respectively; p = 0.009). QRS duration was shorter postoperatively (mean change from preoperative, -32 +/- 24 ms; p < 0.0001); this change was unrelated to surgical approach. Impedance also was less postoperatively (mean change, -490 +/- 300 ohms; p < 0.0001), and the change was unrelated to surgical approach. Changes were greater the larger their preoperative values (p < 0.0001). Threshold increased with follow-up time (adjusted p < 0.0001), but impedance decreased (adjusted p = 0.0009); these trends were similar for both approaches. No changes were evident in left ventricular dimensions. CONCLUSIONS: Minimally invasive left ventricular epicardial lead placement is safe and effective, offering selection of the best pacing site with minimal morbidity; it can be considered a primary option for resynchronization therapy.
Aged↗
Non-invasive evaluation of orthotopic heart transplant rejection by echocardiography.
BACKGROUND: Heart transplant recipients require frequent myocardial biopsies to screen for acute rejection. The purpose of this study was to identify demographic and echocardiographic factors associated with transplant rejection and develop a predictive model, which may reduce the number of cardiac biopsies. METHODS: From January 1998 to December 2001, we performed 406 echocardiographic studies on 264 heart transplant patients who had biopsies performed on the same day. Two-dimensional, pulsed and tissue Doppler echocardiographic variables were compared between patients with and without rejection, and their predictive ability for detecting rejection was determined by uni- and multivariate analyses. RESULTS: In 268 biopsies there was no significant rejection (ISHLT Grade <==II), whereas 138 showed rejection (ISHLT Grade > or =IIIa). By multivariate analysis, pericardial effusion, isovolumic relaxation time (IVRT) <90 milliseconds and mitral inflow E/A ratio >1.7, diameter of inferior vena cava and duration of pulmonary vein atrial reversal were independently associated with rejection. Because the odds ratios were similar for all 5 predictors, a simplified model was developed based on the sum of the number of abnormal predictors present (0 to 5). The probability of rejection increased from 15.9%, in the absence of any predictor, to 39.7%, 52.0% and 71.1%, if 1, 2 or 3 predictors were present, respectively. CONCLUSIONS: Recipient age, pericardial effusion, IVRT and ratio of pulsed Doppler E/A are significant predictors of acute cardiac allograft rejection. However, no single predictor or combination of predictors were powerful enough to eliminate surveillance endomyocardial biopsies.
Adult↗
Brain natriuretic peptide levels do not correlate with acute cellular rejection in De Novo orthotopic heart transplant recipients.
BACKGROUND: The changes in brain natriuretic peptide (BNP) levels after orthotopic heart transplantation have not been previously described. The use of brain natriuretic peptide levels as a surrogate marker for cellular rejection remains controversial, with conflicting data. METHODS: We prospectively evaluated the potential utility of BNP levels in the first 6 months after transplantation and sought correlation with histologic grade of rejection and hemodynamic status. RESULTS: Thirty-five patients and 265 biopsy samples were included in the study. BNP levels did not correlate with histologic grade of rejection. They showed good correlation with central venous pressure and pulmonary capillary wedge pressure. BNP levels were elevated after transplant and showed a steep time-dependent decline. BNP levels correlated with echocardiographically derived indices of diastolic dysfunction. CONCLUSIONS: BNP levels are not a surrogate marker for rejection in the first 2 months after orthotopic heart transplantation and do not obviate the necessity for endomyocardial biopsy. Whether BNP levels have long-term prognostic significance is unclear and remains the subject of ongoing prospective study.
Acute Disease↗
Systemic activation of integrin alphaVbeta3 in donors with spontaneous intracerebral hemorrhage is associated with subsequent development of vasculopathy in the heart transplant recipient.
BACKGROUND: Recipients of hearts from donors with spontaneous intracerebral hemorrhage (ICH) are at increased risk of allograft vasculopathy compared with trauma donors. We have recently shown that the vitronectin receptor (integrin alpha(V)beta3) is upregulated in transplant vasculopathy. We hypothesized that donor ICH is associated with systemic activation of alpha(V)beta3 in the donor before transplantation. METHODS: We evaluated mRNA expressions of alpha(V)beta3 (TaqMan PCR) in endomyocardial biopsy samples at 1-week post-transplant in 20 recipients from ICH donors and 20 recipients from trauma donors. To investigate whether systemic activation of alpha(V)beta3 was present in the donor before transplantation, alpha(V)beta3 expression was also evaluated in the corresponding donor spleen lymphocytes. All patients underwent serial coronary intravascular ultrasound to evaluate for coronary vasculopathy. The baseline characteristics were similar except for increased donor age in the ICH Group. RESULTS: The ICH Group showed significant increased mRNA expression of alpha(V)beta3 in the heart biopsy samples (3.8-fold, p = 0.012) and in the corresponding donor spleen lymphocytes (3.5-fold, p = 0.014) compared with the Trauma Group. At 1 year, the ICH Group also showed increased progression of coronary vasculopathy. Multivariate regression analysis found that donor lymphocytic alpha(V)beta3 mRNA expression was independently associated with increased risk of vasculopathy (odds ratio, 1.9; 95% CI, 1.21-3.98, p = 0.03). CONCLUSIONS: Our report demonstrates the presence of systemic activation of alpha(V)beta3 in donors with spontaneous intracerebral hemorrhage and its association with the subsequent development of allograft vasculopathy in the recipient.
Base Sequence↗
The effect of combined Angiotensin-converting enzyme inhibition and calcium antagonism on allograft coronary vasculopathy validated by intravascular ultrasound.
BACKGROUND: Hypertension is a potential risk factor for allograft coronary vasculopathy. We evaluated the efficacy of angiotensin-converting enzyme (ACE) inhibitors and calcium antagonists, and their combined use, on the development of coronary vasculopathy in hypertensive heart transplant recipients. METHODS: Eighty-two heart transplant recipients underwent serial intravascular ultrasound (IVUS) analysis at baseline (within 1 month) and at 1 year after transplantation and were evaluated for the development of coronary vasculopathy. Patients were divided into 4 groups. Nineteen normotensive recipients received no treatment, control (Group A). Hypertensive patients were treated with either ACE inhibitors (Group B, n = 37), calcium antagonists (Group C, n = 16), or both (Group D, n = 10). RESULTS: We found a significant reduction in IVUS indices of coronary vasculopathy in heart transplant recipients who used a combination of an ACE inhibitor and a calcium antagonist compared with recipients who used either drug alone (p < 0.05). This synergistic efficacy was independent of the baseline indices evaluated in a multivariate regression analysis model and was noted despite comparable mean arterial pressure among the 3 hypertensive groups at 1 year, thus suggesting the presence of a synergistic anti-proliferative effect beyond the anti-hypertensive efficacy. CONCLUSIONS: The combined use of an ACE inhibitor and a calcium antagonist is more effective than the individual use of either drug alone on the development of coronary vasculopathy in cardiac transplant recipients. Large randomized clinical trials are warranted to evaluate such a synergistic efficacy.
Aged↗
The impact of CytoGam on cardiac transplant recipients with moderate hypogammaglobulinemia: a randomized single-center study.
BACKGROUND: We have previously shown that the preemptive use of cytomegalovirus (CMV) immunoglobulin (Ig) replacement (CytoGam) decreases the incidence of opportunistic infections in cardiac transplant recipients with severe hypogammaglobulinemia. However, the impact of Ig replacement in moderately hypogammaglobulinemic patients is unknown. METHODS: Periodic monitoring of the IgG levels was done in 300 heart transplant recipients. Moderate hypogammaglobulinemia (IgG, 350-500 mg/dl) developed in 56 patients (18.6%). Thirty-three patients declined randomization but agreed to have their IgG levels monitored. Twenty-three patients were randomized to placebo (n = 10) or CytoGam (n = 13) at 105 +/- 63 days after transplantation. RESULTS: The baseline characteristics were similar. A significant reduction in CMV infection was noted in the CytoGam Group compared with the Placebo Group (15.4% [2/13] vs 60% [6/10], p = .039). Among patients who declined randomization, CMV infection developed in 13 (39.4%) of 33, and 6 (46.1%) of the 13 progressed to severe hypogammaglobulinemia. A trend for reduction in the average episodes of > or =grade 2 rejection during the 6-month period after randomization was noted in the CytoGam group (0.4 +/- 0.6 vs 1.4 +/- 1.3, p = 0.065). CONCLUSIONS: The preemptive use of CytoGam decreases the incidence of CMV infection in patients with moderate hypogammaglobulinemia. A larger randomized study is needed to substantiate these results.
Adult↗
The impact of donor gender on cardiac peri-transplantation ischemia injury.
BACKGROUND: Cardiac allografts from female donors have been shown to be associated with increased risk of transplant vasculopathy. However, the influence of donor gender on peri-transplantation ischemic injury has not been evaluated. METHODS: A total of 361 patients (mean age, 52 +/- 10 years) underwent cardiac transplantation between January 1998 and December 2002. Patients were divided into 4 groups according to their donor-recipient gender status: Group A, male-male, 156; Group B, male-female, 37; Group C, female-male, 114; and Group D, female-female, 54. Serial right ventricular endomyocardial biopsy specimens were evaluated for ischemic injury during the first 4 weeks after transplantation. RESULTS: Patients were similar in baseline characteristics. An increased incidence of ischemic injury complicated by fibrosis (12.9%, p = 0.03) and subsequent development of transplant vasculopathy (Kaplan-Meier 6-year freedom from vasculopathy, 53.4%; p = 0.012) was noted in Group D. No survival difference was observed among the 4 groups, however. In Group D (F-F), 2 patients underwent retransplantation and 2 patients underwent revascularization. CONCLUSIONS: The transplantation of a female cardiac allograft into a female recipient is associated with increased risk of ischemic injury complicated by fibrosis and subsequent transplant vasculopathy.
Adult↗
Residual high incidence of ventricular arrhythmias after left ventricular reconstructive surgery.
OBJECTIVE: Left ventricular reconstruction is performed in patients with ischemic cardiomyopathy and akinetic or dyskinetic left ventricular regions. These patients may remain at risk for malignant ventricular arrhythmias and hence may benefit from prophylactic implantable cardioverter-defibrillators. Specific guidelines for electrophysiologic testing and implantable cardioverter-defibrillator implantation in patients undergoing left ventricular reconstruction are lacking. We aimed to assess the residual risk and timing of ventricular arrhythmias after left ventricular reconstruction to determine whether electrophysiologic risk stratification or implantable cardioverter-defibrillator implantation can be safely deferred. METHODS: Data were prospectively gathered on 217 consecutive patients with left ventricular ejection fractions less than 40% undergoing left ventricular reconstruction at our institution from 1997 to 2002. Patients were divided into 3 groups: group 1, implantable cardioverter-defibrillator present before surgery; group 2, implantable cardioverter-defibrillator implanted early after surgery; and group 3, no implantable cardioverter-defibrillator implanted. End points were all-cause mortality (censored for cardiac transplantation) and appropriate implantable cardioverter-defibrillator therapies. RESULTS: Of 217 patients (mean age, 61 +/- 10 years [mean +/- SD]), survival after a median follow-up of 381 days was 90%. Electrophysiologic studies successfully identified patients at low risk. Appropriate implantable cardioverter-defibrillator therapies occurred in 20% of group 1 and 12% of group 2. The median time to the first implantable cardioverter-defibrillator therapy from the time of left ventricular reconstruction was 43 days, and most first therapies (67%) occurred within the first 63 days. CONCLUSIONS: The early event rates (occurring in the first 90 days after left ventricular reconstruction) support the use of predischarge electrophysiologic studies, implantation of implantable cardioverter-defibrillators before discharge from the hospital, or both.
Adult↗
Therapeutic drug monitoring for everolimus in heart transplant recipients: flawed model or a model for future use?
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Azathioprine↗
Combined minimally invasive pulmonary vein isolation, left atrial appendage excision and cardiac resynchronization therapy for heart failure: case report.
A 76-year-old male with ischemic cardiomyopathy presented with heart failure symptoms in the absence of angina. Several hospitalizations were required due to heart failure exacerbation and paroxysmal atrial fibrillation. Electrocardiography and tissue synchronization imaging confirmed ventricular dyssynchrony, requiring biventricular pacing. After a failed attempt of percutaneous placement of the left ventricular lead, a novel minimally invasive approach was indicated. It consisted of left ventricular epicardial lead placement, microwave pulmonary vein isolation, and left atrial appendage excision through bilateral minithoracotomies. The postoperative recovery was unremarkable, with reestablishment of the ventricular synchrony and regular rhythm.
Aged↗
Genetics and cardiomyopathy: where are we now?
Many cases of cardiomyopathy have a genetic component: 90% of cases of hypertrophic cardiomyopathy are familial, and genetic factors may be responsible for 30% to 50% of cases of dilated cardiomyopathy. Clinical genetic testing for hypertrophic cardiomyopathy is becoming available, with significant implications for the clinician. This article gives an overview of how these genetic discoveries were made and how these new insights from genetics will affect clinical practice.
Cardiomyopathy, Dilated↗
Tricuspid valve repair for biopsy-induced regurgitation in a heart transplant recipient.
Tricuspid regurgitation (TR) is a frequent complication after heart transplantation. The etiology of TR is multifactorial, but biopsy-induced flail leaflet is one of the most important mechanisms. A 61-year-old woman underwent heart transplant, but experienced several rejection episodes which required multiple surveillance endomyocardial biopsies. At three months after transplant, she required tricuspid valve repair due to symptomatic severe TR. The anterior leaflet was flail, with rupture of primary and secondary chordae. Valve repair was performed with a triple leaflet edge-to-edge technique. The procedure consisted of suture fixation of the prolapsed anterior leaflet joining to the septal and posterior leaflets, and placement of a 30-mm annuloplasty ring. The patient was uneventfully discharged home on day 7 with trivial TR. At a four-years post-transplant evaluation, she was in NYHA functional class I, with preserved ventricular function and trivial TR. She has been followed closely because of post-transplant coronary artery disease.
Biopsy↗
Preload-adjusted right ventricular maximal power: concept and validation.
Right ventricular (RV) maximal power (PWR(mx)) is dependent on preload. The objective of this study was to test our hypothesis that the PWR(mx) versus end-diastolic volume (EDV) relationship, analogous to the load-independent stroke work (SW) versus EDV relationship (preload-recruitable SW, PRSW), is linear, with the PWR x-axis intercept (V(0PWR)) corresponding to the PRSW intercept (V(0SW)). If our hypothesis is correct, the preload sensitivity of PWR(mx) could be eliminated by adjusting for EDV and V(0PWR). Ten dogs were instrumented with a pulmonary flow probe, micromanometers, and RV conductance catheter. Data were obtained during bicaval occlusions under various conditions and fitted to PWR(mx) = a.(EDV - V(0PWR))(beta), where a is the slope of the relationship. The PWR(mx) versus EDV relationship did not deviate from linearity (beta = 1.09, P = not significant vs. 1), and V(0PWR) correlated with V(0SW) (r = 0.93, P <0.0001). V(0PRW) was related to steady-state EDV and left ventricular end-diastolic pressure, allowing for estimation of V(0PWR) (V(0Est)) and single-beat PWR(mx) preload adjustment. Dividing PWR(mx) by the difference of EDV and V(0PWR) (PAMP(V0PWR)) eliminated preload dependency down to 50% of the baseline EDV. PWR(mx) adjustment using V(0Est) (PAMP(V0Est)) showed similar preload independency. Enhancing contractility increased PAMP(V0PWR) and PAMP(V0Est) from 176 +/- 52 to 394 +/- 205 W/ml x 10(4) and 145 +/- 51 to 404 +/- 261 W/ml x 10(4), respectively, accompanied by an increase of PRSW from 13.0 +/- 4.5 to 29.7 +/- 16.4 mmHg (all P <0.01). PAMP(V0PWR) and PAMP(V0Est) correlated with PRSW (r = 0.85; r = 0.77; both P <0.001). Numerical modeling confirmed the accuracy of our experimental data. Thus preload adjustment of PWR(mx) should consider a linear PWR(mx) versus EDV relationship with distinct V(0PWR). PAMP(V0PWR) is a preload-independent estimate of RV contractility that may eventually be determined noninvasively.
Animals↗
Angiotensin II receptors from peritransplantation through first-year post-transplantation and the risk of transplant coronary artery disease.
OBJECTIVES: We evaluated whether the angiotensin II (Ang II) receptors from perioperation through one-year post-transplantation predict the transplant coronary artery disease (TCAD) progression. BACKGROUND: The role of Ang II receptors (type 1: AT(1)R; type 2: AT(2)R) in TCAD is uncertain. METHODS: We investigated 28 heart donors and the corresponding recipients. The levels of AT(1)R and AT(2)R messenger ribonucleic acid (mRNA) were examined in lymphocytes from the donor spleen and in the donor heart at one-week and one-year posttransplantation to determine their association with the progression of TCAD, measured as changes in maximal intimal thickness (CMIT) and plaque volume (CPV) by intravascular ultrasound (IVUS) examinations. RESULTS: The AT(1)R mRNA in lymphocytes from the donor spleen (CMIT: r = 0.73, p < 0.0001; CPV: r = 0.69, p < 0.0001) and in the donor hearts at one-week (CMIT: r = 0.52, p = 0.005; CPV: r = 0.56, p = 0.002) and at one-year (CMIT: r = 0.63, p < 0.0001; CPV: r = 0.43, p = 0.004) post-transplantation along with AT(2)R mRNA in the donor hearts at one-year post-transplantation (CMIT: r = 0.3, p < 0.0001; CPV: r = 0.53, p = 0.009) were univariate predictors, whereas AT(1)R mRNA in lymphocytes and in the donor hearts at one-year post-transplantation proved to be multivariate predictors of the progression of TCAD. CONCLUSIONS: These data suggest a role for Ang II receptors in the pathogenesis of TCAD and support a novel concept that TCAD may have its origin in the donor per se and may be modulated by the recipient's inherent biological factors.
Adult↗
Plasma B-type natriuretic peptide levels in systolic heart failure: importance of left ventricular diastolic function and right ventricular systolic function.
OBJECTIVES: This study was designed to characterize the importance of echocardiographic indexes, including newer indexes of diastolic function, as determinants of plasma B-type natriuretic peptide (BNP) levels in patients with systolic heart failure (SHF). BACKGROUND: Plasma BNP levels have utility for diagnosing and managing heart failure. However, there is significant heterogeneity in BNP levels that is not explained by left ventricular size and function alone. METHODS: In 106 patients with symptomatic SHF (left ventricular ejection fraction [LVEF] <0.35), we measured plasma BNP levels and performed comprehensive echocardiography with assessment of left ventricular diastolic function, including color M-mode (CMM) and tissue Doppler imaging (TDI), and of right ventricular (RV) function. RESULTS: Median plasma BNP levels were elevated and increased with greater severity of diastolic dysfunction. We found significant correlations (p < 0.001 for all) between BNP and indexes of myocardial relaxation (early diastolic velocity: r = -0.26), compliance (deceleration time: r = -0.55), and filling pressure (early transmitral to early annular diastolic velocity ratio: r = 0.51; early transmitral flow to the velocity of early left ventricular flow propagation ratio: r = 0.41). In multivariate analysis, overall diastolic stage, LVEF, RV systolic dysfunction, mitral regurgitation (MR) severity, age and creatinine clearance were independent predictors of BNP levels (model fit r = 0.8, p < 0.001). CONCLUSIONS: Plasma BNP levels are significantly related to newer diastolic indexes measured from TDI and CMM in SHF. Heterogeneity of BNP levels in patients with SHF reflects the severity of diastolic abnormality, RV dysfunction, and MR in addition to LVEF, age, and renal function. These findings may explain the powerful relationship of BNP to symptoms and prognosis in SHF.
Aged↗