Paul Kurlansky

Impact of community-wide police car deployment of automated external defibrillators on survival from out-of-hospital cardiac arrest

Background—Disappointing survival rates from out-of-hospital cardiac arrests encourage strategies for faster defibrillation, such as use of automated external defibrillators (AEDs) by nonconventional responders. Methods and Results—AEDs were provided to all Miami-Dade County, Florida, police. AED-equipped police (P-AED) and conventional emergency medical rescue (EMS) responders are simultaneously deployed to possible cardiac arrests. Times from 9-1-1 contact to the scene were compared for P-AED and concurrently deployed EMS, and both were compared with historical EMS experience. Survival with P-AED was compared with outcomes when EMS was the sole responder. Among 420 paired dispatches of P-AED and EMS, the mean±SD P-AED time from 9-1-1 call to arrival at the scene was 6.16±4.27 minutes, compared with 7.56±3.60 minutes for EMS (P <0.001). Police arrived first to 56% of the calls. The time to first responder arrival among P-AED and EMS was 4.88±2.88 minutes (P <0.001), compared with a historical response time of 7.64±3.66 minutes when EMS was the sole responder. A 17.2% survival rate was observed for victims with ventricular fibrillation or pulseless ventricular tachycardia (VT/VF), compared with 9.0% for standard EMS before P-AED implementation (P =0.047). However, VT/VF benefit was diluted by the observation that 61% of the initial rhythms were nonshockable, reducing the absolute survival benefit among the total study population to 1.6% (P-AED, 7.6%; EMS, 6.0%). Conclusions—P-AED establishes a layer of responders that generate improved response times and survival from VT/VF. There was no benefit for victims with nonshockable rhythms.

Thirty-Year Follow-Up Defines Survival Benefit for Second Internal Mammary Artery in Propensity-Matched Groups

BACKGROUND The value of the left internal mammary artery (LIMA) graft is well established. However, the incremental value of a second IMA graft is controversial. Despite reports of improved survival with bilateral IMA (BIMA) grafting, the Society of Thoracic Surgeons reports its use in 4% of coronary artery bypass graft operations. We report the influence of BIMA vs SIMA grafting on hospital and late mortality in comparable groups. METHODS Retrospective review was conducted of 4584 consecutive isolated coronary artery bypass graft operations (2369 SIMA and 2215 BIMA) performed from 1972 to 1994. The influence of the second IMA was assessed by multivariate analyses of risk factors associated with hospital and late mortality and by propensity score analysis that compares patients with similar baseline characteristics for receiving a second IMA graft. All patients were monitored clinically to assess outcomes. RESULTS Hospital mortality was 4.5% for SIMA vs 2.6% for BIMA patients (p = 0.001). When stratified by propensity score to undergo BIMA grafting, no difference in hospital mortality was found. Multivariate analyses showed SIMA grafting was significantly associated with late but not hospital mortality. Survival curves after 52,572 patient-years of follow-up (mean, 11.5 years; range, 6 weeks to 32 years) demonstrated improved long-term survival for BIMA vs SIMA patients in all quintiles except those with the greatest propensity for SIMA, wherein late survival was comparable between groups. In matched groups, survival favored BIMA patients (p = 0.001). CONCLUSIONS BIMA grafting offers a long-term survival advantage over SIMA grafting in propensity-matched groups.

Design, Synthesis, and Actions of a Novel Chimeric Natriuretic Peptide: CD-NP

OBJECTIVES Our aim was to design, synthesize and test in vivo and in vitro a new chimeric peptide that would combine the beneficial properties of 2 distinct natriuretic peptides with a biological profile that goes beyond native peptides. BACKGROUND Studies have established the beneficial vascular and antiproliferative properties of C-type natriuretic peptide (CNP). While lacking renal actions, CNP is less hypotensive than the cardiac peptides atrial natriuretic peptide and B-type natriuretic peptide but unloads the heart due to venodilation. Dendroaspis natriuretic peptide is a potent natriuretic and diuretic peptide that is markedly hypotensive and functions via a separate guanylyl cyclase receptor compared with CNP. METHODS Here we engineered a novel chimeric peptide CD-NP that represents the fusion of the 22-amino acid peptide CNP together with the 15-amino acid linear C-terminus of Dendroaspis natriuretic peptide. We also determined in vitro in cardiac fibroblasts cyclic guanosine monophosphate-activating and antiproliferative properties of CD-NP. RESULTS Our studies demonstrate in vivo that CD-NP is natriuretic and diuretic, glomerular filtration rate enhancing, cardiac unloading, and renin inhibiting. CD-NP also demonstrates less hypotensive properties when compared with B-type natriuretic peptide. In addition, CD-NP in vitro activates cyclic guanosine monophosphate and inhibits cardiac fibroblast proliferation. CONCLUSIONS The current findings advance an innovative design strategy in natriuretic peptide drug discovery and development to create therapeutic peptides with favorable properties that may be preferable to those associated with native natriuretic peptides.

Bilateral Internal Mammary Artery Grafting Enhances Survival in Diabetic Patients: A 30-Year Follow-Up of Propensity Score-Matched Cohorts

Background— The prevalence of diabetes mellitus is increasing at an unprecedented rate, affecting nearly 8% of the population. Previous studies have demonstrated a potential benefit for surgical over interventional revascularization in this group of patients. Similarly, studies have shown the superiority of bilateral internal mammary artery (BIMA) grafting over single internal mammary artery (SIMA) grafting in select populations. However, concerns about sternal wound infection have discouraged the use of BIMA grafting in diabetics. Therefore, we studied the long-term results of BIMA versus SIMA grafting in a large population of diabetic patients in whom BIMA grafting was broadly applied. Methods and Results— Between February 1972 and May 1994, 1107 consecutive diabetic patients underwent coronary artery bypass grafting with either SIMA (n=646) or BIMA (n=461) grafting. Optimal matching with the propensity score was used to create matched SIMA (n=414) and BIMA (n=414) cohorts. Cross-sectional follow-up (6 weeks to 30.1 years; mean, 8.9 years) determined long-term survival. There was no difference in operative mortality, sternal wound infection, or total complications between matched SIMA and BIMA groups (operative mortality, 10 of 414 [2.4%] versus 13 of 414 [3.1%]; P =0.279; sternal wound infection, 7 of 414 [1.7%] versus 13 of 414 [3.1%]; P =0.179); total complications, 71 of 414 [17.1%] versus 71 of 414 [17.1%]; P =1.000). Late survival was significantly enhanced with the use of BIMA grafting (median survival: SIMA, 9.8 years versus BIMA, 13.1 years; P =0.001). Use of BIMA was found to be associated with late survival on Cox regression ( P =0.003). Conclusion— Compared with SIMA grafting, BIMA grafting in propensity score–matched patients provides diabetics with enhanced survival without any increase in perioperative morbidity or mortality. # Clinical Perspective {#article-title-42}Background— The prevalence of diabetes mellitus is increasing at an unprecedented rate, affecting nearly 8% of the population. Previous studies have demonstrated a potential benefit for surgical over interventional revascularization in this group of patients. Similarly, studies have shown the superiority of bilateral internal mammary artery (BIMA) grafting over single internal mammary artery (SIMA) grafting in select populations. However, concerns about sternal wound infection have discouraged the use of BIMA grafting in diabetics. Therefore, we studied the long-term results of BIMA versus SIMA grafting in a large population of diabetic patients in whom BIMA grafting was broadly applied. Methods and Results— Between February 1972 and May 1994, 1107 consecutive diabetic patients underwent coronary artery bypass grafting with either SIMA (n=646) or BIMA (n=461) grafting. Optimal matching with the propensity score was used to create matched SIMA (n=414) and BIMA (n=414) cohorts. Cross-sectional follow-up (6 weeks to 30.1 years; mean, 8.9 years) determined long-term survival. There was no difference in operative mortality, sternal wound infection, or total complications between matched SIMA and BIMA groups (operative mortality, 10 of 414 [2.4%] versus 13 of 414 [3.1%]; P=0.279; sternal wound infection, 7 of 414 [1.7%] versus 13 of 414 [3.1%]; P=0.179); total complications, 71 of 414 [17.1%] versus 71 of 414 [17.1%]; P=1.000). Late survival was significantly enhanced with the use of BIMA grafting (median survival: SIMA, 9.8 years versus BIMA, 13.1 years; P=0.001). Use of BIMA was found to be associated with late survival on Cox regression (P=0.003). Conclusion— Compared with SIMA grafting, BIMA grafting in propensity score–matched patients provides diabetics with enhanced survival without any increase in perioperative morbidity or mortality.

Recurrent Third-Trimester Fetal Loss and Maternal Mosaicism for Long-QT Syndrome

Background—The importance of germ-line mosaicism in genetic disease is probably underestimated, even though recent studies indicate that it may be involved in 10% to 20% of apparently de novo cases of several dominantly inherited genetic diseases. Methods and Results—We describe here a case of repeated germ-line transmission of a severe form of long-QT syndrome (LQTS) from an asymptomatic mother with mosaicism for a mutation in the cardiac sodium channel, SCN5A. A male infant was diagnosed with ventricular arrhythmias and cardiac decompensation in utero at 28 weeks and with LQTS after birth, ultimately requiring cardiac transplantation for control of ventricular tachycardia. The mother had no ECG abnormalities, but her only previous pregnancy had ended in stillbirth with evidence of cardiac decompensation at 7 months’ gestation. A third pregnancy also ended in stillbirth at 7 months, again with nonimmune fetal hydrops. The surviving infant was found to have a heterozygous mutation in SCN5A (R1623Q), previously reported as a de novo mutation causing neonatal ventricular arrhythmia and LQTS. Initial studies of the mother detected no genetic abnormality, but a sensitive restriction enzyme–based assay identified a small (8% to 10%) percentage of cells harboring the mutation in her blood, skin, and buccal mucosa. Cord blood from the third fetus also harbored the mutant allele, suggesting that all 3 cases of late-term fetal distress resulted from germ-line transfer of the LQTS-associated mutation. Conclusions—Recurrent late-term fetal loss or sudden infant death can result from unsuspected parental mosaicism for LQTS-associated mutations, with important implications for genetic counseling.

Bilateral internal thoracic artery grafting improves long-term survival in patients with reduced ejection fraction: A propensity-matched study with 30-year follow-up

OBJECTIVE Bilateral internal thoracic artery (BITA) grafting has been shown to improve long-term survival after coronary artery bypass grafting. However, there has been reluctance to use this technique in higher-risk patients. Patients with reduced ejection fraction (EF) have been shown to present a higher operative risk and reduced long-term survival. We studied the perioperative and long-term results of BITA versus single internal thoracic artery grafting (SITA) in a large population of patients with reduced EF in whom BITA grafting was broadly applied. METHODS Between February 1972 and May 1994, 4537 consecutive patients in whom EF was recorded underwent SITA (2340) or BITA (2197) grafting. Prospectively collected clinical data recorded EF categorically as less than 0.30 (group I; n = 233), 0.30 to 0.50 (group II; n = 1256), or greater than 0.50 (group III; n = 3048). Multivariable analyses were performed to determine correlates of operative and late mortality. Optimal matching using propensity scoring was used to create matched SITA and BITA cohorts: group I, SITA and BITA, n = 87 each; group II, SITA and BITA, n = 448 each; group III, SITA and BITA, n = 1137 each. Equality of survival distribution was tested by the log-rank algorithm. RESULTS There was no difference in operative mortality between matched SITA and BITA groups (group I: SITA vs BITA, 10.3% vs 6.9%, P = .418; group II: 4.7% vs 4.5%, P = .873; group III: 3.2% vs 2.0%, P = .086). SITA versus BITA was not a predictor of operative mortality on logistic regression analysis. There was no difference in freedom from any postoperative complication, including sternal wound infection, between matched SITA and BITA groups. Late survival was significantly enhanced with the use of BITA grafting in groups II and III (10- and 20-year survival, SITA vs BITA, in group II: 57.7% ± 0.3% and 19% ± 2.5% vs 62.0% ± 2.3% and 33.1% ± 3.4%, respectively, P = .016; and in group III: 67.1% ± 1.4% and 35.8% ± 1.7% vs 74.6% ± 1.3% and 38.1% ± 2.1%, respectively, P = .012). Likewise, choice of SITA versus BITA was a significant predictor of late mortality on Cox regression in both groups II (P < .007) and III (P < .001). CONCLUSIONS Broadly applied BITA compared with SITA grafting in propensity-matched patients provides enhanced long-term survival with no increase in operative mortality or morbidity for patients with normal and reduced EF. The expanded use of BITA grafting should be seriously considered.

Location of the second internal mammary artery graft does not influence outcome of coronary artery bypass grafting.

BACKGROUND Although the use of two internal mammary arteries (IMA) in coronary artery bypass graft surgery has been associated with improved patient survival and clinical status, the optimal use of the second IMA graft remains controversial. We, therefore, explored clinical outcomes in a large cohort of patients undergoing bilateral IMA grafting. METHODS Between February 1972 and May 1994, 2,215 consecutive patients underwent bilateral IMA grafting. The second IMA was used to revascularize the left coronary system (LCS) in 1,479 and the right coronary system (RCS) in 736 patients. Propensity score optimal matching algorithm was used to create the matched LCS group (n=730) and RCS group (n=730). Cross-sectional follow-up (6 weeks to 32.1 years; mean 12.8; 96.7% complete) was performed. Multivariable analyses were performed to determine correlates of operative mortality and late mortality. Patient clinical status and Short Form-36 scores of late survivors were compared. RESULTS There was no difference in either operative mortality or late survival between LCS and RCS patients, in either unmatched or matched groups. Operative mortality unmatched was LCS 38 of 1,479 (2.6%) versus RCS 20 of 736 (2.7%; p=0.837). For matched groups, it was LCS 13 of 730 (1.8%) versus RCS 20 of 736 (2.7%; p=0.284). Median survival in unmatched patients was LCS 15.8 years versus RCS 16.1 years (p=0.803); for matched patients, it was LCS 16.1 years versus RCS 16.1 years (p=0.671). Site of second IMA was not associated with either operative mortality or late survival on multivariable analysis. At follow-up, both groups demonstrated excellent clinical outcomes, with 98.4% of LCS patients and 96.8% of RCS patients in Canadian Cardiovascular Society class I or II, and no significant difference in either the physical (p=0.142) or mental (p=0.542) health summary scores on the Short Form-36. CONCLUSIONS Use of two IMA grafts demonstrates excellent long-term results with no demonstrable difference in outcome between RCS and LCS patients.

Original articleAdult cardiacThe STS AVR + CABG Composite Score: A Report of the STS Quality Measurement Task Force

BACKGROUND The Society of Thoracic Surgeons (STS) is developing a portfolio of composite performance measures for the most commonly performed adult cardiac procedures. This manuscript describes the third composite measure in this series, aortic valve replacement (AVR) combined with coronary artery bypass grafting surgery (CABG). METHODS We identified all patients in the STS Adult Cardiac Surgery Database who underwent AVR+CABG during recent 3-year (July 1, 2009, through June 30, 2012) and 5-year (July 1, 2007, through June 30, 2012) periods. Variables from the STS risk model for AVR+CABG were used to adjust morbidity and mortality outcomes. Evidence for internal mammary artery use in AVR+CABG was examined. We compared composite measures constructed using 3 or 5 years of outcomes with Bayesian credible intervals of 90%, 95%, or 98%. The final STS AVR+CABG composite performance measure is based on 3 years of data and 95% credible intervals. It includes risk-adjusted mortality and morbidity but not internal mammary artery use. RESULTS Median composite score is 91.0% (interquartile range, 89.5% to 92.2%). There were 2.6% (24 of 915) one-star (lower performing) and 6.5% (59 of 915) three-star (higher performing) programs. Morbidity and mortality decrease monotonically as star ratings increase. The percentage of three-star programs increased substantially among programs that performed more than 150 procedures over 3 years compared with those performing 25 to 50 procedures (32.8% versus 1.6 %). Measure reliability was 0.51. CONCLUSIONS The STS has developed a composite performance measure for AVR+CABG based on 3-year data samples and 95% credible intervals. This composite measure identified 9.1% of STS participants as having higher or lower than expected performance.

Bilateral internal mammary artery grafting in women: A 21-year experience

BACKGROUND Coronary artery bypass grafting traditionally has carried a higher mortality rate in women than in men. It remains the leading cause of death in women despite major advances in diagnosis and treatment over the past 2 decades. METHODS A retrospective analysis was conducted to identify risk factors that adversely influence hospital mortality, morbidity, and long-term clinical results in women undergoing bilateral internal mammary artery grafting. From January 1972 through October 1994, 327 consecutive women received bilateral internal mammary artery grafts and supplemental vein grafts. Patient age ranged from 32 to 84 years (mean, 65.7 years). There were 262 patients (80.1%) with three-vessel disease; 71 (21.7%) had substantial (> 50%) stenosis of the left main coronary artery, 65 (19.9%) had a moderately reduced (0.30 to 0.50) ejection fraction, and 11 (3.4%) had a severely reduced (< 0.30) ejection fraction. Preoperatively, 316 patients (96.6%) were in New York Heart Association class III or IV. RESULTS There were 1,016 coronary artery grafts (mean, 3.1 per patient). The overall hospital mortality rate was 3.4% (11 of 327). Postoperative complications included myocardial infarction in 18 patients (5.5%), stroke in 5 (1.5%), pulmonary insufficiency in 11 (3.4%), reoperation for bleeding in 7 (2.1%), and sternal infection in 8 (2.4%). Independent predictors of operative death were postoperative cardiac arrest (p < 0.001), use of intraaortic balloon pump (p < 0.001), and reoperation for bleeding (p < 0.050). Follow-up was completed on 316 hospital survivors (100%) and ranged from 6 months to 21 years (mean, 5.1 years). Actuarial survival (mean +/- standard error of the mean) was 90.5% +/- 1.9% at 5 years and 65.6% +/- 6.1% at 10 years. At follow-up, 252 patients (94.0%) were asymptomatic in New York Heart Association class I, and 12 (4.5%) were in class II. CONCLUSIONS This longitudinal study demonstrates that bilateral internal mammary artery grafting, though technically demanding, can be achieved in women with low hospital mortality and morbidity rates. Patients experienced reduced late cardiac events, excellent functional improvement, and enhanced long-term survival.

In vivo upregulation of nitric oxide synthases in healthy rats

Periodic acceleration (pGz), sinusoidal motion of the whole body in a head-foot direction in the spinal axis, is a novel noninvasive means for cardiopulmonary support and induction of pulsatile shear stress. pGz increases plasma nitrite levels, in vivo and in vitro. Additionally, pGz confers cardioprotection in models of ischemia reperfusion injury. We hypothesize that pGz may also confer a cardiac phenotypic change by upregulation of the expression of the various NO synthase (NOS) isoforms in vivo. pGz was applied for 1h to awake restrained male rats at 2 frequencies (360 and 600 cpm) and acceleration (Gz) of +/-3.4 m/s(2). pGz did not affect arterial blood gases or electrolytes. pGz significantly increased total nitrosylated protein levels, indicating increased NO production. pGz also increased mRNA and protein levels of eNOS and nNOS, and phosphorylated eNOS in heart. pGz increased Akt phosphorylation (p-AKT), but not total Akt, or phosphorylated ERK1/2. Inducible (i) NOS levels were undetectable with or without pGz. Immunoblotting revealed the localization of nNOS, exclusively in cardiomyocyte, and pGz increased its expression. We have demonstrated that pGz changes myocardial NOS phenotypes. Such upregulation of eNOS and nNOS was still evident 24h after pGz. Further studies are needed to understand the biochemical and biomechanical signal transduction pathway for the observed NOS phenotype changed induced by pGz.