bluuebunny/crossref_metadata_2025 huggingface dataset:
Risk Stratification for Coronary Bypass Surgery in Patients With Left Ventricular Dysfunction
Authors: Argenziano Michael , Spotnitz Henry M. , Whang William , Bigger J. T. , Parides Michael , Rose Eric A.
Published: July 2021

Background
—Preoperative characteristics may influence morbidity and mortality in patients undergoing coronary artery bypass grafting (CABG). The CABG Patch Trial was designed to assess the impact of prophylactic insertion of an implantable cardioverter-defibrillator in patients undergoing high-risk CABG. This database was used to investigate the influence of symptomatic congestive heart failure (CHF) and angina on morbidity and mortality in CABG patients with ventricular dysfunction.

Methods and Results
—Data were analyzed for 900 randomized patients with an ejection fraction ≤35% and an abnormal signal-averaged ECG. Single-variable and stepwise multiple logistic regression analyses were used for mortality and length-of-stay (LOS) data. Severity of CHF and angina was graded by the New York Heart Association (NYHA) and Canadian Cardiovascular Society (CCS) classifications, respectively. Perioperative mortality was 3.5% in 454 patients without clinical signs of heart failure versus 7.7% in 443 patients with NYHA class I to IV heart failure (
P
=0.018). By multiple logistic regression analysis, mortality was significantly higher in patients with preoperative symptomatic (NYHA class I to IV) heart failure (odds ratio, 2.4;
P
=0.01) or reoperation (odds ratio, 3.8;
P
<0.0001). Mortality was not significantly influenced by age, sex, the presence or severity of angina, hypertension, left main coronary artery disease, pulmonary disease, or severity of CHF (although LOS was increased 0.7 days per NYHA class). Patients with a history of stroke had a higher rate of perioperative stroke (16.4% versus 3.6%,
P
=0.001) and an increased LOS (by 3.5 days).

Conclusions
—Symptomatic heart failure and reoperation are predictors of increased operative mortality in patients with ventricular dysfunction and a positive signal-averaged ECG. Conversely, patients without heart failure symptoms may undergo CABG with relatively low mortality despite low ejection fraction. LOS is prolonged significantly by advanced age, history of stroke, and the presence and severity of heart failure.
Intermediate-Term Clinical Outcome Following Transmyocardial Laser Revascularization in Patients With Refractory Angina Pectoris
Authors: Landolfo Carolyn K. , Landolfo Kevin P. , Hughes G. Chad , Coleman Edward R. , Coleman Robin B. , Lowe James E.
Published: July 2021

Background
—This study was conducted to examine the intermediate-term clinical outcomes in patients with refractory angina pectoris treated with transmyocardial laser revascularization (TMR) at our institution. TMR is an alternative surgical technique for the treatment of myocardial ischemia and angina pectoris not amenable to conventional percutaneous or surgical revascularization. Limited data exist evaluating the natural history and duration of clinical improvement in angina pectoris following TMR.

Methods and Results
—Thirty-four patients with severe coronary artery disease unsuitable for treatment with standard revascularization techniques underwent TMR in myocardial regions determined to be ischemic by preoperative SPECT
201
Tl perfusion imaging following dipyridamole stress. Patients were assessed postoperatively at 3, 6, and 12 months for clinical outcomes including death, myocardial infarction, functional class of angina pectoris, and hospitalizations for unstable angina. Myocardial perfusion imaging by
201
Tl scintigraphy was also assessed at these temporal end points. Overall mortality at 1 year was 14.7% (n=5). Nonfatal myocardial infarction occurred in 3 patients (8.8%). Among the patients with complete 12-month follow-up (n =27), mean anginal class improved from 3.5±0.5 pre-TMR to 2.8±0.7 and 2.5±0.7 at 3 and 6 months, respectively, and 2.8±0.9 at 12 months. Overall improvement in angina pectoris was sustained at 1 year by at least one functional class in 50% of patients. Mean hospitalizations per year for unstable angina declined from 2.4±1.6 pre-TMR to 1.7±2.0 post-TMR (
P
=0.01). There was no significant improvement in perfusion by SPECT
201
Tl imaging at any temporal end point post-TMR.

Conclusions
—Despite the lack of demonstrable improvement in perfusion by SPECT
201
Tl imaging, TMR improved the functional class of angina pectoris in patients with end stage coronary artery disease to a modest degree. Although the maximal benefit in symptoms occurred at 6 months post-TMR, mild sustained clinical improvement above baseline was evident in 50% of patients at 1 year.
Measurement of Myocardial Blood Flow With Positron Emission Tomography Before and After Transmyocardial Laser Revascularization
Authors: Rimoldi Ornella , Burns Sharon M. , Rosen Stuart D. , Wistow Trevor E. , Schofield Peter M. , Taylor Gordon , Camici Paolo G.
Published: July 2021

Background
—Transmyocardial laser revascularization (TMLR) has been proposed for treatment of refractory angina. It has been hypothesized that transmural left ventricular channels created by laser improve myocardial blood flow (MBF) in the treated zones. We aimed to assess the effect of TMLR on MBF and coronary vasodilator reserve (CVR).

Methods and Results
—We measured MBF by means of PET with
15
O-labeled water in 7 patients with refractory angina, Canadian Cardiovascular Society (CCS) class 3.6±0.5, on 3 occasions: before and at 7.5±2.8 weeks (FU-1) and 34.6±4.7 weeks (FU-2) after TMLR performed with a synchronized, high-powered CO
2
laser. In each study, MBF was measured at rest and during maximal intravenous dobutamine. CVR was computed as dobutamine divided by resting MBF. After TMLR, CCS class was 2.2±1.7 at FU-1 and 2.4±1 at FU-2 (
P
=0.04 versus pre-TMLR). Resting MBF in both lasered and nonlasered regions was unchanged after TMLR. Dobutamine MBF at baseline was 1.45±0.52 and 1.55±0.52 mL · min
−1
· g
−1
in lasered and nonlasered regions, respectively (
P
=NS). At FU-1, dobutamine MBF in nonlasered regions had increased significantly to 1.89±0.82 mL · min
−1
· g
−1
(
P
<0.05) and was higher than in lasered regions (1.51±0.61 mL · min
−1
· g
−1
;
P
<0.05 versus nonlasered). At FU-2, dobutamine MBF in nonlasered regions was still higher than in lasered regions (1.56±0.54 versus 1.21±0.44 mL · min
−1
· g
−1
;
P
<0.01). CVR was comparable in nonlasered and lasered regions at baseline and FU-1, whereas it was higher in nonlasered regions at FU-2 (1.86±0.67 versus 1.53±0.72 mL · min
−1
· g
−1
;
P
<0.05).

Conclusions
—TMLR has been shown to reduce angina in severely diseased patients. The results of our study do not support the hypothesis that the symptomatic benefit of TMLR can be ascribed to improved myocardial perfusion or CVR in lasered areas.
Repair of Tetralogy of Fallot in Neonates and Young Infants
Authors: Pigula Frank A. , Khalil Philipe N. , Mayer John E. , del Nido Pedro J. , Jonas Richard A.
Published: July 2021

Background
—The timing of repair of tetralogy of Fallot (TOF) remains controversial. Advantages to early complete repair include removal of right ventricular outflow tract obstruction, alleviation of systemic hypoxia, and avoidance of palliation with an arteriopulmonary shunt.

Methods and Results
—This is a retrospective review of 99 children with TOF pulmonary stenosis (TOF/PS) or TOF pulmonary atresia (TOF/PA) who were <90 days of age undergoing early complete repair. Fifty-nine were prostaglandin E dependent, and 91% of neonates were symptomatic at the time of repair. Univariate and multivariate analyses of patient characteristics, anatomic features, and operative management showed the diagnosis of TOF/PA and smaller body surface area to be the only independent risk factors for death. Early mortality was 3% (3 of 99), and actuarial survival rates were 94% at 1 year and 91.6% at 5 years. Freedom from catheterization was 86% at 1 year and 73% at 5 years. Patients repaired for TOF/PA had a significantly lower freedom from reoperation than did those repaired for TOF/PS.

Conclusions
—Early complete TOF repair can be accomplished with a low mortality. Children with TOF/PA repaired had a lower freedom from reoperation that did those with TOF/PS. Longer follow-up, with emphasis on arrhythmias and right ventricular function, is required to define the long-term benefits of early repair.
Surgical Patent Foramen Ovale Closure for Prevention of Paradoxical Embolism–Related Cerebrovascular Ischemic Events
Authors: Dearani Joseph A. , Ugurlu Baran S. , Danielson Gordon K. , Daly Richard C. , McGregor Christopher G. A. , Mullany Charles J. , Puga Francisco J. , Orszulak Thomas A. , Anderson Betty J. , Brown Robert D. , Schaff Hartzell V.
Published: July 2021

Background
—The role of surgical closure of patent foramen ovale (PFO) for cerebral infarction (CI) or transient ischemic attack (TIA) resulting from paradoxical embolism is unclear, and its effect on recurrence is unknown. Our objective was to determine the outcome of surgical closure of PFO in patients with a prior ischemic neurological event, define the rate of CI or TIA recurrence after PFO closure, and identify risk factors for these recurrences.

Methods and Results
—We retrospectively analyzed 91 patients (58 men, 33 women) with ≥1 previous cerebrovascular ischemic events who underwent surgical PFO closure between April 1982 and March 1998. The presence of a PFO with a right-to-left shunt was confirmed with transesophageal echocardiography. Mean age was 44.2±12.2 years. The index event was a CI in 59 and a TIA in 32; a Valsalva-like episode preceded the event in 15 patients. Deep venous thrombosis was documented in 9 patients, and a hypercoagulable state was identified in 10. Surgical closure was performed with extracorporeal circulation by either direct suture (n=82) or patch closure (n=9). Limited incisions were used in 18.7% of patients. There was no operative mortality. Morbidity included transient atrial fibrillation (n=11), pericardial drainage for effusion (n=4), exploration for bleeding (n=3), and superficial wound infection (n=1). Follow-up totaled 176.3 patient-years, and mean follow-up was 2.0 years. No one had a CI, and 8 had a TIA during follow-up, with 1 caused by temporal arteritis. Transesophageal echocardiography demonstrated all closures to be intact in these patients. The overall freedom from TIA recurrence during follow-up was 92.5±3.2% at 1 year and 83.4±6.0% at 4 years. Having multiple neurological events before PFO closure was the only significant risk factor for TIA or CI recurrence after closure by univariate analysis (
P
=0.05); the small number of post-PFO closure cerebral ischemic events precluded multivariate analysis.

Conclusions
—Surgical closure of PFO can be performed with minimal morbidity and mortality. PFO closure may decrease the risk of recurrent stroke or TIA and may avoid lifelong anticoagulation in the young adult if there is no other indication. Recurrent cerebrovascular ischemic events after surgery should prompt further evaluation to identify causes other than paradoxical embolism.
Impaired Glucose Transporter Activity in Pressure-Overload Hypertrophy Is an Early Indicator of Progression to Failure
Authors: Friehs Ingeborg , Moran Adrian M. , Stamm Christof , Colan Steven D. , Takeuchi Koh , Cao-Danh Hung , Rader Christine M. , McGowan Francis X. , del Nido Pedro J.
Published: July 2021

Background
—Severe hypertrophy and heart failure are important risk factors in cardiac surgery. Early adaptive changes in hypertrophy include increased ventricular mass-to-cavity volume ratio (M/V ratio) and increased dependence on glucose for energy metabolism. However, glucose uptake is decreased in the late stages of hypertrophy when ventricular dilatation and failure are present. We hypothesized that impaired glucose uptake would be evident early in the progression of hypertrophy and associated with the onset of ventricular dilatation.

Methods and Results
—Ten-day-old rabbits underwent banding of the descending aorta. Development of hypertrophy was followed by transthoracic echocardiography to measure left ventricular M/V ratio. Glucose uptake rate, as determined by
31
P-nuclear magnetic resonance spectroscopy measuring 2-deoxyglucose conversion to 2-deoxyglucose-6-phosphate, was measured in isolated perfused hearts obtained from banded rabbits when M/V ratio had increased by 15% from baseline (compensated hypertrophy) and by 30% from baseline (early-decompensated hypertrophy). In age-matched control animals, the rate of glucose uptake was 0.61±0.08 μmol · g of wet weight
−1
· 30 min
−1
(mean±SEM). With a 15% M/V ratio increase, glucose uptake rate remained at control levels (0.6±0.05 μmol · g of wet weight
−1
· 30 min
−1
), compared with hearts with 30% increased M/V ratios, where glucose uptake was significantly lower (0.42±0.05 μmol · g of wet weight
−1
· 30 min
−1
;
P
≤0.05). Glucose transporter protein expression was the same in all groups.

Conclusions
—Glucose uptake rate is maintained during compensated hypertrophy. However, coinciding with severe hypertrophy, preceding ventricular dilatation, and glucose transporter protein downregulation, glucose uptake is significantly decreased. Because of the increased dependence of the hypertrophied hearts on glucose use, we speculate that this impairment may be a contributing factor in the progression to failure.
Myocardial Gene Expression of Regulators of Myocyte Apoptosis and Myocyte Calcium Homeostasis During Hemodynamic Unloading by Ventricular Assist Devices in Patients With End-Stage Heart Failure
Authors: Bartling Babett , Milting Hendrik , Schumann Heike , Darmer Dorothea , Arusoglu Lativ , Koerner Michael Matthias , El-Banayosy Aly , Koerfer Reiner , Holtz Juergen , Zerkowski Hans-Reinhard
Published: July 2021

Background
—In patients with end-stage heart failure, characterized by an increased susceptibility to cardiomyocyte apoptosis and a labile cardiomyocyte calcium homeostasis, a ventricular assist device (VAD) is implanted for bridging to cardiac transplantation and results in myocardial unloading. Although phenotype changes in the failing heart are assumed to result from hemodynamic overload, the reversibility of these changes under unloading is unknown.

Methods and Results
—By use of quantitative reverse-transcription polymerase chain reaction, mRNA expression analyses were performed on left ventricular specimens obtained from 10 nonfailing donor hearts (from 8 patients with dilated cardiomyopathy and 2 patients with coronary heart disease) at the time of VAD implantation and 36 to 169 days later during VAD removal with subsequent cardiac transplantation. In terminally failing hearts before VAD support, left ventricular mRNA analyses revealed increased Pro-ANP, reduced antiapoptotic Bcl-x
L
and antiapoptotic Fas isoform FasExo6Del, and a decreased ratio of sarcoplasmic reticulum Ca
2+
-ATPase per sarcolemmal Na
+
-Ca
2+
exchanger in comparison with nonfailing ventricles. After VAD unloading, ventricular transcription of Pro-ANP was immediately normalized, and apoptotic DNA fragmentation was attenuated. In patients with dilated cardiomyopathy, mRNAs of Bcl-x
L
and FasExo6Del/Fas were enhanced depending on time on VAD. The Bcl-x
L
mRNA level correlated positively with that of the Bcl-x
L
protein. Transcription of sarcoplasmic reticulum Ca
2+
-ATPase/Na
+
-Ca
2+
exchanger demonstrated recovery in only 4 of 10 patients.

Conclusions
—Mechanical support of the failing heart induces a time-dependent change in myocardial gene expression compatible with a decreased susceptibility to apoptosis.
Physiological and Hemodynamic Evaluation of Nonuniform Direct Cardiac Compression
Authors: Artrip John H. , Yi Geng-Hua , Levin Howard R. , Burkhoff Daniel , Wang Jie
Published: July 2021

Background
—Biventricular direct cardiac compression (DCC) has the potential to support the failing heart without the complications associated with a blood/device interface encountered with the use of current ventricular assist devices. A clinically designed DCC device that provides compression pressure around the base of the heart in synchrony with native ventricular contractions was evaluated with the use of an ex vivo and in vivo canine model of heart failure.

Methods and Results
—The device was tested over a series of ventricular preloads with the use of an ex vivo canine heart preparation and computerized afterload system that mimicked the conditions of heart failure. The end-systolic pressure-volume relation of the left and right ventricles was shifted upward in parallel by DCC, with the magnitude of the shift averaging 40% of the device compression pressure. The device was tested in vivo with the use of a canine model of acute ischemic heart failure in which graded reductions in ventricular function were created through serial coronary artery embolizations. Under the most severe condition of heart failure, DCC improved cardiac output (CO) by 104% (0.80±0.33 to 1.63±0.40 L/min) and mean arterial pressure by 95% (45.6±11 to 89.0±18.2 mm Hg). The CO was typically restored to ≈60% of the normal baseline value, despite attempts to further increase CO by increasing the amount or duration of compression pressure.

Conclusions
—Nonuniform DCC significantly improves the left and right ventricular pressure-generating capability and, in the setting of acute heart failure, can increase CO and mean arterial pressure. Such DCC devices can potentially avoid the complications associated with currently available ventricular support devices that involve a blood/device interface.
Autologous Transplantation of Bone Marrow Cells Improves Damaged Heart Function
Authors: Tomita Shinji , Li Ren-Ke , Weisel Richard D. , Mickle Donald A. G. , Kim Eung-Joong , Sakai Tetsuro , Jia Zhi-Qiang
Published: July 2021

Background
—Autologous bone marrow cells (BMCs) transplanted into ventricular scar tissue may differentiate into cardiomyocytes and restore myocardial function. This study evaluated cardiomyogenic differentiation of BMCs, their survival in myocardial scar tissue, and the effect of the implanted cells on heart function.

Methods and Results
—In vitro studies: BMCs from adult rats were cultured in cell culture medium (control) and medium with 5-azacytidine (5-aza, 10 μmol/L), TGFβ1 (10ng/mL), or insulin (1 nmol/L) (n=6, each group). Only BMCs cultured with 5-aza formed myotubules which stained positively for troponin I and myosin heavy chain. In vivo studies: a cryoinjury-derived scar was formed in the left ventricular free wall. At 3 weeks after injury, fresh BMCs (n=9), cultured BMCs (n=9), 5-aza–induced BMCs (n=12), and medium (control, n=12) were autologously transplanted into the scar. Heart function was measured at 8 weeks after myocardial injury. Cardiac-like muscle cells which stained positively for myosin heavy chain and troponin I were observed in the scar tissue of the 3 groups of BMC transplanted hearts. Only the 5-aza–treated BMC transplanted hearts had systolic and developed pressures which were higher (
P
<0.05) than that of the control hearts. All transplanted BMCs induced angiogenesis in the scar.

Conclusions
—Transplantation of BMCs induced angiogenesis. BMCs cultured with 5-aza differentiated into cardiac-like muscle cells in culture and in vivo in ventricular scar tissue and improved myocardial function.
Unilateral Antegrade Cerebral Perfusion Through the Right Axillary Artery Provides Uniform Flow Distribution to Both Hemispheres of the Brain
Authors: Ye Jian , Dai Guangping , Ryner Lawrence N. , Kozlowski Piotr , Yang Luojia , Summers Randy , Sun Jiankang , Salerno Tomás A. , Somorjai Rajmund L. , Deslauriers Roxanne
Published: July 2021

Background
—Bilateral antegrade cerebral perfusion (ACP) has decreased in popularity over the past decade because of its complexity and the risk of cerebral embolism. We used magnetic resonance (MR) perfusion imaging to assess flow distribution in both hemispheres of the brain during unilateral ACP through the right carotid artery via a cannula placed in the right axillary artery in conjunction with hypothermic circulatory arrest.

Methods and Results
—Twelve pigs were randomly exposed to 120 minutes of either bilateral ACP through both carotid arteries (n=6) or unilateral ACP through the right axillary artery (n=6) at pressures of 60 to 65 mm Hg at 15°C, followed by 60 minutes of cardiopulmonary bypass at 37°C. MR perfusion images were acquired every 30 minutes before, during, and after ACP. The brain was perfusion fixed for histopathology. During initial normothermic cardiopulmonary bypass, MR perfusion imaging showed a uniform distribution of flow in the brain. In both the bilateral and unilateral ACP groups, the same pattern was maintained, with an increase in regional cerebral blood volume during ACP and reperfusion. The changes in regional cerebral blood volume and mean transit time were similar in both hemispheres during and after unilateral ACP. No difference was observed between the 2 groups. Histopathology showed normal morphology in all regions of the brain in both groups.

Conclusions
—Both bilateral ACP and unilateral ACP provide uniform blood distribution to both hemispheres of the brain and preserve normal morphology of the neurons after prolonged hypothermic circulatory arrest.
RSR13, a Synthetic Allosteric Modifier of Hemoglobin, Improves Myocardial Recovery Following Hypothermic Cardiopulmonary Bypass
Authors: Kilgore Kenneth S. , Shwartz Charles F. , Gallagher Marsha A. , Steffen Robert P. , Mosca Ralph S. , Bolling Steven F.
Published: July 2021

Background
—During hypothermic blood cardioplegia, oxygen delivery to myocytes is minimal with ineffective anaerobic metabolism predominating. RSR13, 2-[4-[[(3,5-dimethylanilino) carbonyl]methyl]phenoxy]-2-methylpropionic acid, a synthetic allosteric modifier of hemoglobin (Hb), increases release of oxygen from Hb, increasing oxygen availability to hypoxic tissues, and reverses the hypothermia-dependent increase in Hb oxygen affinity. We studied recovery of myocardial mechanical and metabolic function and examined myocardial morphology after cardioplegia, comparing RSR13 (1.75 mmol/L)-supplemented blood (RSR13-BC) to standard blood cardioplegia (BC).

Methods and Results
—Twelve dogs underwent 15 minutes of 37°C global ischemia on cardiopulmonary bypass, followed by 75 minutes of hypothermic cardioplegia (13°C) with either BC (n=6) or RSR13-BC (n=6). There were no differences in baseline function between groups. Cardiac function was assessed after 30 minutes of 37°C reperfusion (BC versus RSR13-BC, respectively) by measuring: % return to normal sinus rhythm (0/100%), % of baseline+dP/dt (33.7±1.7/76.3±1.9), % of baseline−dP/dt (26.6±2.0/81.1±1.6), stroke volume (3.5±0.5/7.1±0.9 mL), cardiac output (340±20/880±40.3 mL/min), and LVEDP (11.3±2.2/0.3±2.9 mm Hg). Postischemic oxidative and metabolic parameters including myocardial lactate, pyruvate, ATP content, and percent water content also were determined. Histological analysis demonstrated preservation of endothelial and myocyte morphology in hearts receiving RSR13-BC compared with BC.

Conclusions
—These results indicate that in the setting of hypothermic cardiopulmonary bypass, RSR13 improves recovery of myocardial mechanical and metabolic function compared with standard hypothermic BC. Findings from this study suggest that RSR13-BC, by decreasing hemoglobin oxygen affinity, improves oxidative metabolism and preserves cellular morphology, resulting in significantly improved contractile recovery on reperfusion.
Early Clinical Results After Stentless Mitral Valve Implantation and Comparison With Conventional Valve Repair or Replacement
Authors: Walther Thomas , Walther Claudia , Falk Volkmar , Diegeler Anno , Krakor Ralf , Schneider Johannes , Autschbach Rüdiger , Mohr Friedrich W.
Published: July 2021

Background
—A new quadricusp stentless mitral bioprosthetic valve (QMV) is evaluated and compared with current standards.

Methods and Results
—Since August 1997, 67 patients were prospectively evaluated: 23 patients received a QMV, 23 had mitral valve repair (MVR), and 21 received conventional mitral valve replacement (MVP). Patient age was 69±8, 64±10, and 62±9 years for QMV, MVR, and MVP treatment, respectively. The underlying pathology was mitral stenosis, incompetence, and mixed disease in a corresponding 8, 9, and 6 patients for QMV, 1, 22, and 0 patients for MVR, and 2, 12, and 7 patients for MVP. The papillary muscles were sufficient in all QMV cases to suspend the valve. Cross-clamp time was 59±19 minutes for QMV implantation. In-hospital mortality for QMV, MVR, and MVP was 1, 0, and 0 patients, respectively, and thoracotomy had to be performed again in 1, 1, and 2 patients, respectively (these outcomes were not valve related). At baseline transthoracic echocardiography, respective maximum flow velocities were 1.6, 1.4, and 1.7 m/s, and valve orifice area was 2.6, 3.5, and 3.4 cm
2
. Mild transvalvular reflux was seen in 8, 7, and 2 patients; moderate reflux, in 1, 1, and 1 patients. Left ventricular ejection fraction was 52%, 54%, and 51% in the respective treatment groups. At follow-up, hemodynamic parameters had further improved in all groups.

Conclusions
—One year after clinical implantation, the QMV appears to function well and has no additional risks compared with MVR or MVP. The subvalvular apparatus is preserved by suspending the QMV at the papillary muscles; this arrangement is hemodynamically advantageous. Echocardiography reveals an excellent valve performance that resembles native mitral valve morphology and hemodynamic function. The QMV is a promising alternative for biological mitral valve replacement.
Real-Time Three-Dimensional Echocardiographic Study of Left Ventricular Function After Infarct Exclusion Surgery for Ischemic Cardiomyopathy
Authors: Qin Jian Xin , Shiota Takahiro , McCarthy Patrick M. , Firstenberg Michael S. , Greenberg Neil L. , Tsujino Hiroyuki , Bauer Fabrice , Travaglini Agnese , Hoercher Kathy J. , Buda Tiffany , Smedira Nicholas G. , Thomas James D.
Published: July 2021

Background
—Infarct exclusion (IE) surgery, a technique of left ventricular (LV) reconstruction for dyskinetic or akinetic LV segments in patients with ischemic cardiomyopathy, requires accurate volume quantification to determine the impact of surgery due to complicated geometric changes.

Methods and Results
—Thirty patients who underwent IE (mean age 61±8 years, 73% men) had epicardial real-time 3-dimensional echocardiographic (RT3DE) studies performed before and after IE. RT3DE follow-up was performed transthoracically 42±67 days after surgery in 22 patients. Repeated measures ANOVA was used to compare the values before and after IE surgery and at follow-up. Significant decreases in LV end-diastolic (EDVI) and end-systolic (ESVI) volume indices were apparent immediately after IE and in follow-up (EDVI 99±40, 67±26, and 71±31 mL/m
2
, respectively; ESVI 72±37, 40±21, and 42±22 mL/m
2
, respectively;
P
<0.05). LV ejection fraction increased significantly and remained higher (0.29±0.11, 0.43±0.13, and 0.42±0.09, respectively,
P
<0.05). Forward stroke volume in 16 patients with preoperative mitral regurgitation significantly improved after IE and in follow-up (22±12, 53±24, and 58±21 mL, respectively,
P
<0.005). New York Heart Association functional class at an average 285±144 days of clinical follow-up significantly improved from 3.0±0.8 to 1.8±0.8 (
P
<0.0001). Smaller end-diastolic and end-systolic volumes measured with RT3DE immediately after IE were closely related to improvement in New York Heart Association functional class at clinical follow-up (Spearman’s ρ=0.58 and 0.60, respectively).

Conclusions
—RT3DE can be used to quantitatively assess changes in LV volume and function after complicated LV reconstruction. Decreased LV volume and increased ejection fraction imply a reduction in LV wall stress after IE surgery and are predictive of symptomatic improvement.
What is the Optimal Age for Repair of Tetralogy of Fallot?
Authors: Van Arsdell Glen S. , Maharaj Gyaandeo S. , Tom Julie , Rao Vivek K. , Coles John G. , Freedom Robert M. , Williams William G. , McCrindle Brian W.
Published: July 2021

Background
—Controversy regarding the timing for the repair of tetralogy of Fallot centers around initial palliation versus primary repair for the symptomatic neonate/young infant and the optimal age for repair of the asymptomatic child. We changed our approach from one of initial palliation in the infant to one of primary repair around the age of 6 months, or earlier if clinically indicated. We examined the effects of this change in protocol and age on outcomes.

Methods and Results
—The records of 227 consecutive children who had repair of isolated tetralogy of Fallot from January 1993 to June 1998 were reviewed. The median age of repair by year fell from 17 to 8 months (
P
<0.01). The presence of a palliative shunt at the time of repair decreased from 38% to 0% (
P
<0.01). Mortality (6 deaths, 2.6%) improved with time (
P
=0.02), with no mortality since the change in protocol (late 1995/early 1996). Multivariate analysis for physiological outcomes of time to lactate clearance, ventilation hours, and length of stay, but not death, demonstrated that an age <3 months was independently associated with prolongation of times (
P
<0.03). Each of the deaths occurred with primary repair at an age >12 months. The best survival and physiological outcomes were achieved with primary repair in children aged 3 to 11 months.

Conclusions
—On the basis of mortality and physiological outcomes, the optimal age for elective repair of tetralogy of Fallot is 3 to 11 months of age.
Failure of Stroke Volume Augmentation During Exercise and Dobutamine Stress Is Unrelated to Load-Independent Indexes of Right Ventricular Performance After the Mustard Operation
Authors: Derrick Graham P. , Narang Indra , White Paul A. , Kelleher Andrea , Bush Andrew , Penny Daniel J. , Redington Andrew N.
Published: July 2021

Background
—Impaired right ventricular function has been implicated as a cause of reduced maximal exercise capacity after the Mustard operation for transposition of the great arteries.

Methods and Results
—Fourteen asymptomatic survivors of the Mustard operation were studied. Each underwent conventional cardiac catheterization, and after satisfactory hemodynamics were confirmed, load-independent indexes of ventricular function were derived by conductance catheter during dobutamine infusion (0, 5, and 10 μg · kg
−
1
· min
−
1
). Seven patients also underwent upright exercise testing on a bicycle ergometer with analysis of respiratory gas exchange by continuous mass spectrometry. Accessible pulmonary blood flow was measured at each workload with an automated acetylene rebreathing technique. All patients exercised to a satisfactory end point (respiratory quotient >1.1). Maximum oxygen consumption during exercise was impaired compared with predicted values (mean, 77%;
P
<0.02). Both exercise and dobutamine infusion were associated with an increase in cardiac index and heart rate and a reduced stroke volume index response. This was despite significantly improved indexes of myocardial contraction (end-systolic pressure volume relation,
P
<0.001), preload recruitable stroke work index (
P
<0.01), VA coupling (
P
<0.001), and isovolumic relaxation (
P
<0.001) during dobutamine infusion. There were no changes observed in end-diastolic pressure-volume relations, but there was failure to augment ventricular filling manifest by absence of change in dV/dt (
P
=NS).

Conclusions
—The stroke volume response to exercise stress is reduced in patients after the Mustard operation. A similar failure to augment stroke volume occurs during dobutamine stress despite appropriate responses in load-independent indexes of contraction and relaxation. This is due to failure to augment right ventricular filling rates during tachycardia, presumably as a result of impaired AV transport, consequent to the abnormal intra-atrial pathways.
Pulsatile Flow in Patients With a Novel Nonpulsatile Implantable Ventricular Assist Device
Authors: Potapov Evgenij V. , Loebe Matthias , Nasseri Boris A. , Sinawski Hendryk , Koster Andreas , Kuppe Hermann , Noon George P. , DeBakey Michael E. , Hetzer Roland
Published: July 2021

Background
—Ventricular assist devices (VADs) are an accepted therapy for patients with end-stage heart failure. The implantable devices that are available produce a pulsatile flow and are very large. In 6 patients, beginning in November 1998, we started to use the continuous-flow implantable DeBakey VAD device, which weighs 93 g. To detect the flow in peripheral vessels, we measured transcranial Doppler signals in patients after implantation.

Methods and Results
—Transcranial Doppler studies were performed with the MULTI-DOP X4 device with two 2-MHz probes (for the middle cranial arteries) in 4 patients for up to 12 weeks twice weekly after implantation. The blood velocity was measured, and the pulsation index (PI) calculated. The measured pump flow and rotations per minute were registered. The preoperative echocardiographic assessment values were compared with those acquired 6 weeks after implantation. The PI increased continually in all patients after VAD implantation, left ventricular (LV) ejection fraction did not improve, but right ventricular (RV) ejection fraction after implantation improved compared with preoperative values. The LV end-diastolic diameter after implantation decreased between 11% and 46% intraindividually. There was no correlation between PI and blood pressure or, except in 1 patient, between PI and blood flow through the VAD.

Conclusions
—The DeBakey VAD unloads the LV, which leads to a decrease in LV end-diastolic LV diameter and to the restoration of RV function. The unloaded LV and partially recovered RV provide a nearly physiological pulsatile flow despite the continuous flow of the VAD. Pulsatility is independent of peripheral vascular resistance. The first clinical experience with the DeBakey VAD was positive and has resulted in its continued use.
Heart Cell Transplantation Improves Heart Function in Dilated Cardiomyopathic Hamsters
Authors: Yoo Kyung-Jong , Li Ren-Ke , Weisel Richard D. , Mickle Donald A. G. , Jia Zhi-Qiang , Kim Eung-Joong , Tomita Shinji , Yau Terrance M.
Published: July 2021

Background
—Little is known about the effect of heart cell transplantation into the dilated cardiomyopathic myocardium. This study was designed to evaluate the effect of heart cell transplantation into dilated cardiomyopathic hamsters.

Methods and Results
—Ventricular heart cells were isolated from 4-week-old BIO 53.58 hamsters and cultured for 2 weeks before transplantation. The cells were labeled with bromodeoxyuridine (BrdU) before transplantation for identification. Adult hamsters (17 weeks old) were used as recipients. Heart cells (4×10
6
cells) or culture medium was transplanted into the left ventricular free wall (transplantation and control groups, respectively, n=12 each). Sham-operated hamsters (n=12) underwent the surgery but not the transplantation. Cyclosporine A was administered subcutaneously to all hamsters daily after the operation. Four weeks after the transplantation, heart function was evaluated with the use of a Langendorff preparation. Histology showed severe focal myocardial necrosis in all groups. BrdU-stained tissue was found at the cell transplantation sites. The transplanted hearts had greater (
P
<0.001) developed pressures at all balloon volumes and improved dP/dt (transplantation 915±253 versus control 453±120 and sham 530±187 mm Hg/s,
P
<0.001, balloon volume of 15 μL). No differences in ventricular function were found between control and sham-operated hamsters.

Conclusions
—The transplanted ventricular heart cells formed cardiac-like tissue in cardiomyopathic myocardium and improved its contractile function.
Closed Relation Between Carotid and Ascending Aortic Atherosclerosis in Cardiac Patients
Authors: Kallikazaros Ioannis E. , Tsioufis Costas P. , Stefanadis Christodoulos I. , Pitsavos Christos E. , Toutouzas Pavlos K.
Published: July 2021

Background
—Carotid atherosclerosis and aortic atherosclerosis are both associated with coronary artery disease and cerebral thromboembolism. However, the relationship between asymptomatic carotid and aortic atherosclerosis is not well known.

Methods and Results
—Sixty-two consecutive cardiac patients (mean age 57 years) without a history of atherosclerotic cardiovascular disease who were referred for transesophageal echocardiography were included. By means of a high-resolution ultrasound technique, normal carotid arteries were found in 12 patients (19.4%), whereas 15 patients (24.2%) had increased intima-media thickness, and the remaining 35 patients (56.5%) had atherosclerotic plaques (intima-media thickness ≥1.3 mm). Transesophageal echocardiography characterized ascending aortic intimal morphology as normal in 1 patient (1.6%), as thickening in 22 patients (35.5%), and as atherosclerotic plaques in 39 patients (62.9%). Patients with both carotid and aortic plaques were older compared with patients without plaques; also, a higher percentage of patients with carotid and aortic plaques suffered from hypertension and diabetes mellitus compared with patients without plaques (
P
<0.001). The incidence of carotid plaques was 74.3% (29 of 39 patients) in the subgroup with aortic plaques; there was a stepwise increase in the percentage of patients with carotid plaques among the patients with increasing grades of aortic atherosclerosis. Furthermore, the incidence of ascending aortic plaques was 82.8% (29 of 35 patients) in the subgroup with carotid plaques. Regression analysis revealed that age and carotid plaques were independently related to the presence of aortic plaques. In the entire study population, the presence of carotid plaques had a high positive predictive value (83%), an acceptable sensitivity (75%) and specificity (74%), and a relatively low negative predictive value (63%) for the presence of aortic plaques.

Conclusions
—In cardiac patients without clinical evidence of atherosclerotic cardiovascular disease, a high prevalence of combined aortic and carotid plaques were detected. The presence of carotid plaque reflects the presence of aortic plaque, whereas the absence of carotid plaque may not reflect the absence of aortic plaque.
Gene Transfer of the Serine Elastase Inhibitor Elafin Protects Against Vein Graft Degeneration
Authors: O’Blenes Stacy B. , Zaidi Syed H. E. , Cheah Alexander Y. L. , McIntyre Brendan , Kaneda Yasufumi , Rabinovitch Marlene
Published: July 2021

Background
—Leukocyte infiltration and serine elastase activity lead to smooth muscle cell proliferation in association with posttransplant coronary arteriopathy and may also be involved in vein graft neointimal formation. A number of therapies have targeted cellular proliferation, but the inhibition of serine elastase–mediated extracellular matrix remodeling has not been investigated as a potential strategy to prevent neointimal formation and subsequent atherosclerotic degeneration in vein grafts.

Methods and Results
—We studied jugular vein grafts 48 hours after interposition into the carotid arteries of rabbits and demonstrated inflammatory cell infiltration and elevated serine elastase activity, a stimulus for matrix remodeling and deposition of elastin. Therefore, elastolytic activity in vein grafts was targeted through transient expression of the selective serine elastase inhibitor elafin with hemagglutinating virus of Japan liposome–mediated gene transfer. Elafin transfection reduced inflammation by 60% at 48 hours and neointimal formation by ≈50% at 4 weeks after implantation. At 3 months, a 74% decrease in neointimal elastin deposition correlated with protection against cholesterol-induced macrophage infiltration and lipid accumulation, which were both reduced by ≈50% in elafin-transfected grafts relative to controls.

Conclusions
—Gene transfer of the selective serine elastase inhibitor elafin in vein grafts is effective in reducing the early inflammatory response. Although transient expression of elafin delays neointimal formation, it is also sufficient to cause an alteration in elastin content of the extracellular matrix, making it relatively resistant to atherosclerotic degeneration.
Cryopreservation of Rat Aortic Valves Results in Increased Structural Failure
Authors: Legare Jean Francois , Lee Timothy D. G. , Ross David B.
Published: July 2021

Background
—The cause of valve allograft failure is most likely multifactorial and may include mechanical, immunological, and other factors. Cryopreservation of these valves is often used to extend storage times. However, there has been considerable confusion as to the effects of cryopreservation on valve durability. Our objective was to determine the effects of cryopreservation on histopathological changes in rat aortic valve grafts.

Methods and Results
—Syngeneic rat aortic valve grafts (Lewis to Lewis; n=24) and allogeneic rat aortic valve grafts (Brown Norway to Lewis; n=24) were implanted infrarenally, either fresh or after cryopreservation. At 7, 14, and 28 days, the valves were explanted, and histological and immunohistochemical examinations were performed in a blinded fashion. Fresh syngeneic graft leaflets retained their normal structure for the 28-day period of observation. Cryopreserved syngeneic grafts showed retrovalvar thrombus formation, with leaflet destruction at 7, 14, and 28 days. Fresh allogeneic graft leaflets showed significant leaflet thickening and progressive destruction at 14 and 28 days. Cryopreserved allogeneic grafts had evidence of retrovalvar thrombus formation with leaflet destruction at 7, 14, and 28 days. Cryopreserved syngeneic grafts resulted in significant infiltration of mononuclear (ED1
+
) cells not seen with fresh syngeneic grafts but similar to fresh allogeneic grafts. All allogeneic grafts resulted in significant infiltration of T-lymphocytes (CD3
+
, CD8
+
, CD43
+
).

Conclusions
—Cryopreservation appears to predispose syngeneic and allogeneic rat aortic valve leaflets to accelerated injury and destruction. This mode of failure resembles that of fresh allogeneic valve grafts.
HDL Cholesterol Level Predicts Survival in Men After Coronary Artery Bypass Graft Surgery
Authors: Foody JoAnne Micale , Ferdinand Francis D. , Pearce Gregory L. , Lytle Bruce W. , Cosgrove Delos M. , Sprecher Dennis L.
Published: July 2021

Background
—HDL cholesterol (HDL-C) is an important independent predictor of atherosclerosis, yet the role that HDL-C may play in the prediction of long-term survival after CABG remains unclear. The risk associated with a low HDL-C level in post-CABG men has not been delineated in relation to traditional surgical variables such as the use of arterial conduits, left ventricular function, and extent of disease.

Methods and Results
—We performed a prospective, observational study of 432 men who underwent CABG between 1978 and 1979 in whom preoperative HDL-C values were available. Baseline lipid and lipoprotein values, history of diabetes mellitus and hypertension, left ventricular ejection fraction, extent of disease, and use of internal thoracic arteries were recorded. Hazard ratios (HRs) were determined in the patients with and without a low HDL-C level, which was defined as the lowest HDL-C quartile (HDL-C ≤35 mg/dL). After adjustment for age, as well as for baseline metabolic parameters and surgical variables just noted, HDL-C corresponded to both overall (HR 0.40, CI 0.20 to 0.83,
P
=0.01) and event-free (HR 0.41, CI 0.24 to 0.70,
P
=0.001) survival. Patients with a high HDL-C level (>35 mg/dL) were 50% more likely to survive at 15 years than were patients with low HDL-C level (≤35 mg/dL) (74% versus 57% adjusted survival, respectively; HR 1.72,
P
=0.005). In addition, HDL-C showed a strong effect on time-to-event survival such that patients with an HDL-C level of >35 mg/dL were 50% more likely to survive without a subsequent myocardial infarction or revascularization (HR 1.42,
P
=0.02).

Conclusions
—HDL-C is an important predictor of survival in post-CABG patients. In this study of >8500 patient-years of follow-up, HDL-C was the most important metabolic predictor of post-CABG survival. One third fewer patients survive at 15 years if their HDL-C levels are ≤35 mg/dL at the time of CABG. The measurement of HDL-C provides a compelling strategy for the identification of high-risk subsets of patients who undergo CABG.
Familial Aggregation of Coronary Artery Calcium in Families with Type 2 Diabetes
Authors: Wagenknecht Lynne E. , Langefeld Carl D. , Bowden Donald W. , Carr J. Jeffrey , Freedman Barry I. , Rich Stephen S.
Published: July 2021

P11

Type 2 diabetes is recognized as a major risk factor for atherosclerotic cardiovascular disease including subclinical atherosclerosis as measured by non-invasive procedures. However, the role of genetic factors that contribute to various measures of subclinical atherosclerosis is largely unknown. We hypothesize that subclinical atherosclerosis, measured as coronary artery calcification (CAC), will be extensive in persons with type 2 diabetes, and that its presence depends on both genetic and environmental factors. The genetic factors will result in the familial aggregation of CAC. To determine the extent of familial aggregation of CAC in the presence of type 2 diabetes, we studied 122 persons with type 2 diabetes (mean age 60 years) and 13 persons without diabetes in 56 families. CAC was measured by fast gated helical computed tomography. Other measured factors included blood pressure, body size, lipids, HbA1c, and self-reported medical history. To test for an association between CAC and these factors while accounting for the potential familial correlation of CAC, generalized estimating equations were used. CAC was detectable in 80% of persons with diabetes (median score = 84, range 0 - 5776). Extent of CAC, adjusted for age, was associated with male gender (p=0.0003), reduced HDL (p=0.02), albumin-creatinine ratio (p=0.008), and cigarette pack-years (p=0.03). CAC was also associated with a history of angina, myocardial infarction, stroke and vascular procedure (all p<0.01). HbA1c and fasting glucose were positively, but non-significantly associated with extent of CAC (p=0.14 and 0.08, respectively). CAC, adjusted for age, sex, race and diabetes status was heritable (h

2

= 0.50, p=0.009). In multivariate analysis adjusting for HDL, BMI, hypertension, and smoking, h

2

= 0.40 (p=0.038). These results suggest that strong (independent) genetic factors as well as environmental factors contribute to the variance of CAC in persons with type 2 diabetes. In these data, CAC appears heritable and may serve as an important feature in designing studies to map genes contributing to both atherosclerosis and type 2 diabetes.