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The South Carolina cystic fibrosis (CF) newborn screening (NBS) program changed in 2019 to include CFTR genotyping for babies with top 4% immunoreactive trypsinogen, which improves sensitivity and timeliness but increases carrier detection. Carrier identification has genetic implications for the family and parents of NBS+ babies have increased emotional distress. Genetic counseling (GC) may increase parent understanding and reduce anxiety yet is not uniformly offered at CF centers. We report our early results after implementing GC for NBS+ families at the time of sweat chloride testing based on GC availability, which resulted in an unselected GC- control arm. Sixteen mothers (GC+ = 9, GC- = 7) participated in an online survey about their experience. Responses were analyzed in aggregate and for differences between GC+ and GC- groups. All-respondent sadness and anxiety increased with notification of the NBS+ result and decreased after sweat test results. Anxiety and sadness were greater in GC- compared to GC+ until after the diagnosis was resolved, though emotional differences between the groups were not statistically significant. On a scale of 0 = not at all to 10 = extremely, GC was rated very helpful (mean 9.0, range 5-10), informative (mean 8.9, range 4-10), comforting (mean 9.1, range 6-10), and minimally distracting (mean 1.8, range 0-9). All participants correctly identified that a risk for a child to have CF exists when both parents are (at least) carriers. Delivery of NBS results to respondents varied by timing, informant, and information given. The child's pediatrician notified 10 (62.5%) of the NBS+ result. Parents felt they were notified in a timely manner (68.8%), by someone knowledgeable about NBS (62.5%), the sweat test (62.5%), CF (43.8%), and genetics (43.8%) and who cared about them (81.3%). Parents felt worried (81.3%), confused (81.3%), empowered (25%), and other (sad, shocked, scared, overwhelmed, devastated, defeated). Data from this single-center study suggest benefit of GC, that families would value earlier contact with an expert, and that prompt diagnostic resolution may reduce duration of parental distress., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Strong emphasis has been placed historically on increasing weight and improving nutritional status in cystic fibrosis patients. Due to correlation between nutritional indices (e.g. BMI) and lung function, CF Nutrition Guidelines have recommended BMI percentile goals at the 50th percentile or higher. Trends in increasing BMI across CF programs suggest significantly increasing proportions of overweight and obese status in recent years. We identify that between 2000 and 2019 there has been a relative decrease in underweight status by ∼40%, simultaneously with a > 300% increase in overweight status, and >400% increase in obesity. Patient specific factors associated with higher prevalence of obesity included age ≥46, living in a zip code where the median income was < $20,000, having at least one allele with a class IV or V mutation, a ppFEV 1 >90 prescribed ivacaftor, and not prescribed pancreatic enzymes. Program specific factors were not identified., Competing Interests: Declaration of Competing Interest The authors whose names are listed immediately below certify that they have NO affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers’ bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript., (Copyright © 2022. Published by Elsevier B.V.)

We report elexacaftor-tezacaftor-ivacaftor (ETI) treatment of a F508del carrier who was pregnant with a F508del homozygous fetus. At 23-weeks gestation meconium ileus (MI) was evident on ultrasound including dilated, hyperechoic bowel, which persisted on subsequent imaging. Through shared decision-making, the mother began ETI at 32 weeks with intent to treat fetal MI. The ultrasound findings persisted at treatment day 13, but bowel dilation had resolved by imaging on treatment day 27. A female infant was delivered vaginally at 36 weeks with no complications. The mother continued ETI while breastfeeding. Stool elastase at age 2 weeks was 240 mcg/g. Sweat chloride measurement was 64 and 62 mEq/L. Maternal and infant liver function testing have been normal. Maternal ETI treatment likely led to resolution of the MI and there is evidence supporting continued infant benefit through breastmilk. Logistical and ethical considerations regarding treatment of a carrier mother for infant benefit are discussed., Competing Interests: Declaration of Competing Interest Patrick Flume receives research support and consultation fees from Vertex Pharmaceuticals. All other authors declare no conflict of interest., (Copyright © 2022 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.)

Purpose of Review: Pulmonary exacerbations are described as worsening of the daily symptoms of cystic fibrosis airways disease, typically with increased cough and sputum production. There are often associated signs such as weight loss and reduced lung function. These events occur frequently and are associated with considerable cost and morbidity. Although approved maintenance therapies are shown to reduce exacerbations, they still occur and are associated with poor outcomes despite treatment. Guidelines to define best practices found a paucity of evidence upon which to base recommendations., Recent Findings: There are ongoing studies that are trying to build the evidence upon which to improve our practice. Antibiotics remain a core aspect of treatment, but there is high variance in practice patterns including selection of antibiotics and duration of therapy. In addition, there is a discordance between antibiotic susceptibility test results and clinical outcomes, suggesting we need better approaches to guide antibiotic selection., Summary: Treatment durations are highly variable but recent evidence has demonstrated worse outcomes with shorter durations; longer durations may be associated with complications of treatment, suggesting an optimal duration could be identified. New studies aim to define best practices to improve outcomes with treatment of pulmonary exacerbations.

Background: Lung ventilation defects identified by using hyperpolarized 3-helium gas ((3)He) lung magnetic resonance imaging (MRI) are prevalent in asthmatic patients, but the clinical importance of ventilation defects is poorly understood., Objectives: We sought to correlate the lung defect volume quantified by using (3)He MRI with clinical features in children with mild and severe asthma., Methods: Thirty-one children with asthma (median age, 10 years; age range, 3-17 years) underwent detailed characterization and (3)He lung MRI. Quantification of the (3)He signal defined ventilation defect and hypoventilated, ventilated, and well-ventilated volumes., Results: The ventilation defect to total lung volume fraction ranged from 0.1% to 11.6%. Children with ventilation defect percentages in the upper tercile were more likely to have severe asthma than children in the lower terciles (P = .005). The ventilation defect percentage correlated (P < .05 for all) positively with the inhaled corticosteroid dose, total number of controller medications, and total blood eosinophil counts and negatively with the Asthma Control Test score, FEV1 (percent predicted), FEV1/forced vital capacity ratio (percent predicted), and forced expiratory flow rate from 25% to 75% of expired volume (percent predicted)., Conclusion: The lung defect volume percentage measured by using (3)He MRI correlates with several clinical features of asthma, including severity, symptom score, medication requirement, airway physiology, and atopic markers., (Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

We present a case of an adult patient who had anomalous origin of the right coronary artery (RCA) from the left sinus of Valsalva that had been treated surgically in the past and who presented years later with chest pain and runs of nonsustained ventricular tachycardia. Coronary angiography showed a patent unroofed RCA with appropriately repositioned origin and no obstructive coronary artery disease. This case presents angiographic documentation of a technically satisfactory repair of anomalous aortic origin of a coronary artery and suggests that potentially lethal arrhythmia can occur despite a technically satisfactory repair.

Phosphodiesterase 5 inhibitors are cardioprotective against myocardial reperfusion ischemic injury in animal models but are contraindicated in patients with coronary disease who take nitrates because of a risk for hypotension. We investigated the safety of vardenafil in patients undergoing coronary artery bypass grafting (CABG) surgery. A single dose of vardenafil was given to 10 patients before CABG surgery. The postoperative course of these 10 patients was compared with the postoperative course of 47 patients who did not receive vardenafil before CABG surgery. There were no perioperative deaths and no episodes of hypotension in the group receiving vardenafil. The clinical and operative characteristics of the 2 study groups were similar. There were no significant differences in postoperative serum troponin levels (9.1 ± 8.3 vs 12.5 ± 9.3 ng/mL; P = 0.29, respectively), duration of postoperative intubation (21.4 ± 10.1 vs 27.4 ± 15.2 hours; P = 0.14, respectively), or length of hospital stay (11.1 ± 13.2 vs 10.0 ± 4.7 days; P = 0.8, respectively) between the group receiving vardenafil and the control group. This pilot study of 10 patients suggests that vardenafil use is safe in patients before CABG surgery. A larger study is needed to explore the myocardial protective effect of the drug.

Effective management of patients after the implantation of mechanical cardiac valves includes correct recognition of each valve and its related complications. Herein, we present the case of a patient who had undergone implantation of a floating-disc Beall-Surgitool mitral valve in 1976 and developed multiple valve-related complications. Over 30 years and in multiple medical centers, the device was mistakenly assumed to be a "ball" valve. The correct identification of the prosthesis led to the recognition of valvular failure, and the patient underwent its replacement with an On-X bileaflet carbon valve. Pathologic and microscopic examination of the explanted Beall valve showed massive pannus formation that extended over the sewing cuff on the atrial and ventricular side, preventing complete disc closure; disrupted fabric coating of the sewing ring, with exposure of the underlying metal; and a marked inflammatory reaction. We report one of the longest intervals on record between the implantation and replacement of a Beall-Surgitool valve.

Background and Aim of the Study: This ongoing, longitudinal, multi-center, North American study was designed to evaluate the safety and effectiveness of the On-X valve., Methods: The On-X valve was implanted in isolated aortic (AVR) and mitral (MVR) valve replacement patients at nine North American centers. Follow up was 98.6% complete. Anticoagulation compliance was evaluated by collection of international normalized ratio (INR) results in all patients throughout their postoperative follow up. Adverse events were recorded according to the AATS/STS guidance criteria. Hematologic studies were conducted postoperatively to evaluate hemodynamics and hemolysis., Results: In total, 142 AVR and 142 MVR implants were performed; the mean follow up was 4.5 years; total follow up was 1,273 patient-years (pt-yr). At implant, the mean patient age was 59.2 years (range: 28 to 85 years); 71.8% of patients who underwent AVR and 33.1% who underwent MVR were males. Preoperatively, 89.4% of AVR patients and 56.3% of MVR patients were in sinus rhythm. The cardiac disease etiology was primarily stenotic, calcific degeneration in AVR and rheumatic or degenerative regurgitation in MVR. Hemolysis represented by postoperative elevation of serum lactate dehydrogenase was very low (median 217 IU after AVR and 251 IU after MVR at one year (82% AVR and 98% MVR of upper normal). Late adverse event rates were low, most notably thromboembolism (0.9%/pt-yr after AVR; 1.6%/pt-yr after MVR) and thrombosis. Kaplan-Meier event-free rates at five years were correspondingly high. Anticoagulation compliance analysis showed only about 40% of INR readings to be within target ranges postoperatively; thus, the control range achieved was much greater than the desired target, as might generally be expected for clinic-controlled INR., Conclusion: The On-X valve performed well in this study, confirming the original design intent of minimal hemolysis and low adverse event rates.

Background: In a prospective, randomized trial involving 263 patients who would be incompletely revascularized by coronary artery bypass grafting (CABG) alone, CABG plus transmyocardial revascularization (CABG/TMR) provided an early mortality benefit with similar angina relief compared with CABG alone at 1 year. We evaluated the long-term outcome of patients randomized to CABG/TMR or CABG alone., Methods: Thirteen centers that enrolled 83% (218/263) of the patients in the original trial participated in this longitudinal study. Between 1996 and 1998, these centers randomized 218 patients who would be incompletely revascularized by CABG alone because of diffusely diseased target vessels to either holmium:yttrium-aluminum-garnet (holmium:YAG) CABG/TMR (n = 110) or CABG alone (n = 108). Baseline demographics and operative characteristics were similar between groups. Follow-up (mean 5.0 +/- 1.7 years) included survival and blinded angina class assessment., Results: At this 5-year follow-up both groups experienced significant angina improvement from baseline, however, the CABG/TMR group had a lower mean angina score (0.4 +/- 0.7 vs 0.7 +/- 1.1, p = 0.05), a significantly lower proportion of patients with severe angina (class III/IV: 0% [0/68] vs 10% [6/60], p = 0.009), and a trend towards greater number of angina-free patients (78% [53/68] vs 63% [38/60], p = 0.08), compared with CABG alone patients. Kaplan-Meier survival at 6 years was similar between CABG/TMR and CABG alone patients (76% vs 80%, p = 0.90)., Conclusions: Five-year follow-up of prospectively randomized patients who would be incompletely revascularized because of diffuse coronary artery disease indicates that the addition of TMR to conventional CABG provides superior angina relief compared to CABG alone.

Objective: We sought to assess the safety and efficacy of transmyocardial revascularization combined with coronary artery bypass grafting in patients not amenable to complete revascularization by coronary bypass alone., Methods: A total of 263 patients whose standard of care was coronary artery bypass grafting and who had one or more ischemic areas not amenable to bypass grafting were prospectively randomized to receive coronary bypass of suitable vessels plus transmyocardial revascularization to areas not graftable (n = 132) or coronary bypass alone with nongraftable areas left unrevascularized (n = 131). Group preoperative demographics and operative characteristics were similar., Results: The operative mortality rate after coronary bypass/transmyocardial revascularization was 1.5% (2/132) versus 7.6% (10/131) after coronary bypass alone (P =.02). Patients undergoing both coronary bypass and transmyocardial revascularization required less postoperative inotropic support (30% vs 55%, P =.0001) and had a trend toward fewer insertions of intra-aortic balloon pumps (4% vs 8%, P =.13) than did patients having coronary bypass alone. Multivariable predictors of operative mortality were coronary artery bypass alone (odds ratio, 5.3; 95% confidence interval, 1.1-25.7; P =.04) and increased age (odds ratio, 1.1; 95% confidence interval, 1. 0-1.2; P =.03). One-year Kaplan-Meier survival (95% vs 89%, P =.05) and freedom from major adverse cardiac events defined as death or myocardial infarction (92% vs 86%, P =.09) favored the combination of coronary bypass and transmyocardial revascularization. Baseline to 12-month improvement in angina and exercise treadmill scores was similar between groups., Conclusions: In a prospective, randomized, multicenter trial, transmyocardial revascularization combined with coronary artery bypass grafting in patients not amenable to complete revascularization by coronary bypass alone was safe; however, angina relief and exercise treadmill improvement were indistinguishable between groups at 12 months of follow-up. Operative and 1-year survival benefits observed after adjunctive transmyocardial revascularization require confirmation by a larger validation study, which is ongoing.

Background and Aims of the Study: Combined aortic and mitral valve replacement continues to result in significant morbidity and mortality. Although mitral repair has improved the results of mitral valve surgery, its influence on combined aortic valve replacement has not been assessed., Methods: We reviewed 38 consecutive patients who underwent aortic valve replacement (AVR) and mitral repair (MR) between 1985 and 1995. The average age was 57 years; 20 were men and 18 women. Nineteen patients were considered high risk: six had previous cardiac surgery, three were on chronic dialysis, two required emergency surgery for low output syndrome, one had a chronic tracheotomy for chronic lung disease, and seven had left ventricular ejection fraction < 30%. MR consisted of ring application alone in 28 patients, chordal shortening in nine, posterior leaflet transfer in six and posterior leaflet resection in four. AVR was accomplished with 21 bioprostheses, 14 mechanical and three allograft valves. The mean (+/-SD) cross-clamp time was 133 +/- 41 min. Additional procedures included coronary bypass in six patients and tricuspid procedures in three., Results: There were no operative deaths. Six patients died between 4 and 73 months postoperatively. Patient survival was 75% five and 67% 10 years after surgery. The causes of death were heart failure (two cases), and respiratory failure, drug overdose, electrolyte imbalance and unknown (one each). Logistic risk analysis was significant for females and rheumatic valve disease, bacterial endocarditis, and degenerated valve patients. During follow up there were no valve failures or endocarditis, but three embolic episodes occurred without permanent sequel., Conclusions: With increased surgical expertise, improved myocardial protection of MR combined with AVR offers excellent short- and long-term results, optimal chordal preservation, no valve failure and no endocarditis; it is the ideal choice where anti-coagulation is contraindicated. The prolonged cross-clamp time was well tolerated.

The widespread use of the redesigned Endotak lead (CPI, St. Paul, Minnesota), which combines transvenous pacing, sensing, and defibrillation on a single transvenous lead in patients receiving transvenous implantable cardioverter-defibrillators (ICDs), has reduced morbidity and shortened length of hospital stay after ICD implantation. We describe the incidence and management of Endotak sensing lead-related failures in a series of 348 consecutive patients from 4 institutions who underwent implantation between 1990 and 1995. We retrospectively reviewed the databases for patients receiving an ICD with an Endotak lead for the incidence of lead-related sensing abnormalities. Ten patients (2.8%) with lead-related sensing abnormalities were detected at a mean of 15 +/- 11 months after ICD implantation. Sensing abnormalities were detected in 6 patients after they received inappropriate shocks. Noise or oversensing was noted in 7 patients from interrogation of the devices' data logs. Eight patients had a new transvenous sensing lead placed, 1 patient had a new Endotak lead placed, and 1 had a chronic pacemaker sensing lead converted to function as a sensing lead. No further sensing problems were noted in 8 of 10 patients during a mean follow-up of 14 +/- 8 months. The site of the sensing lead failure was localized to the subrectus pocket in 5 patients and to the clavicle-first rib area in 3 patients; it was undetermined and presumed to be in the clavicle-first rib area in the other 2 patients. One patient had late failure of the defibrillation lead. We conclude that Endotak sensing lead failure does not require insertion of a new Endotak lead, but can be managed with close follow-up and insertion of a new transvenous sensing lead. Endotak lead fractures are frequently localized to the ICD pocket.

Seven patients with complex thoracic aortic aneurysms were operated on using profound hypothermia and circulatory arrest through a left thoracotomy. Three patients had false aneurysms, 2 had large aneurysms precluding access for proximal control, 1 patient had had previous hemiarch replacement, and 1 patient had a thoracoabdominal aneurysm. All patients were cooled on partial cardiopulmonary bypass until the electroencephalogram was isoelectric (approximately 15 degrees C rectal temperature). Circulatory arrest times ranged from 7 to 56 minutes (median, 34 minutes). There was one death due to cardiac failure, and paraplegia developed in 1 patient. The 6 survivors are otherwise well at a median of 12 months postoperatively. Hypothermia and circulatory arrest is an invaluable technique for the treatment of complex aortic aneurysms requiring left thoracotomy for resection. The techniques employed are described and the indications for their use are discussed.

An alternative technique of handling the aortic cannulation site blowout is described. The cannulation site is excluded with a side-biting clamp. The area is excised. Pericardial patch is sewn in to cover the defect.

Herein we report the only two long-term survivors of cardiac transplantation who underwent successful repair of symptomatic abdominal aortic aneurysms since the advent of cyclosporine therapy in 1983. Review of the world's literature indicates that the only two recorded cases of repair of symptomatic abdominal aortic aneurysms after cardiac transplantation occurred before the use of cyclosporine. The presentation and clinical course of our patients recently treated are presented, and perioperative care and immunosuppressive management are outlined. As the number of long-term survivors after cardiac transplantation increases, the incidence of other atherosclerotic complications including abdominal aortic aneurysm is likely to become more common, requiring extended cardiovascular follow-up.

Cyclosporine has gained acceptance as the immunosuppressive agent of choice in cardiac transplantation, but the validity of this assumption has yet to be established. Since January 1983, 25 patients have been randomly assigned to receive either conventional immunosuppression (azathioprine/antithymocyte globulin/prednisone) and pretransplant transfusion (PAAP, n = 11) or cyclosporine immunosuppression (cyclosporine and prednisone [CyA], n = 14). There was no difference in the age distribution (41 +/- 9 vs 38 +/- 11 years), indications for transplantation, preoperative serum creatinine level (1.2 +/- 0.2 vs 1.4 +/- 0.3 mg/dl), or postoperative follow-up time (13.5 +/- 5.4 vs 13.5 +/- 5.2 months). Mortality was not different (PAAP = 2, CyA = 3) and there was no difference in rejection episodes per patient (PAAP = 1.8, CyA = 1.9). Patients in the PAAP group had more serious infections (PAAP = 8, CyA = 3; P less than .02), but those in the CyA group developed a greater incidence of systemic hypertension (PAAP = 1, CyA = 10; p less than .02), pericardial effusion (PAAP = 0, CyA = 6; p = .05), and impaired renal function (creatinine 1.5 mg/dl, PAAP = 2, CyA = 11; p less than .02). Thus it appears that in this small series, cyclosporine is not associated with a significant increase in early survival. It does appear that patients on PAAP immunosuppression develop a greater number of serious infections, but the incidence of rejection episodes appears to be the same. Renal dysfunction and hypertension in patients receiving cyclosporine continue to be long-term concerns and may add to the morbidity and mortality of patients treated with this immunosuppressive regimen.

Fifty-two consecutive patients who underwent orthotopic heart transplantation at our institution were evaluated by two-dimensional (2D) echocardiography at frequent intervals for 12 weeks after transplantation and at three monthly intervals for 1 year. Thirty-eight of 52 patients had adequate 2D echocardiograms and comprised the retrospective study group. Pericardial effusion was documented in 15 of 38 patients (40%). Pericardial effusion was moderate in two (5%) and small in seven patients (18%). Large pericardial effusion was demonstrated in six of 38 patients (16%). Three of 38 patients (8%) developed cardiac tamponade manifested by hypotension in the presence of a large pericardial effusion. The diagnosis of cardiac tamponade was aided by 2D echocardiography leading to prompt pericardiocentesis. The presence of pericardial effusion in patients after their transplantation did not demonstrate independent correlation with chest tube output after operation, cyclosporine therapy, acute rejection, level of blood urea nitrogen (BUN), infection or preoperative diagnosis of idiopathic dilated cardiomyopathy. The presence of cyclosporine therapy, acute rejection, and a preoperative diagnosis of idiopathic dilated cardiomyopathy, however, yielded an 86% probability of having pericardial effusion. Follow-up 2D echocardiograms obtained 301 +/- 106 days after transplantation were available in 25 patients. Fifteen patients (60%) had no pericardial effusion present on either the initial or follow-up 2D echocardiogram. The majority of cases of the pericardial effusion present on initial or follow-up echocardiograms were resolving on the follow-up study.(ABSTRACT TRUNCATED AT 250 WORDS)

Heart period variability and arterial baroreceptor-cardiac reflex function were studied in cardiac transplant patients to determine if correction of heart failure restores parasympathetic control mechanisms toward normal. Heart period variability (standard deviation [SD] of 120 consecutive RR or PP intervals) was measured at supine rest in 34 patients with congestive heart failure (23 patients receiving diuretics, digoxin or vasodilators and 11 patients weaned from all medications), 30 cardiac transplant patients (both innervated recipient and denervated donor atrial rates) and 16 age-matched healthy control subjects. Arterial baroreflex gain was evaluated with intravenous bolus injections of phenylephrine in 22 transplant patients. Mean heart period variability (+/- SEM) was significantly lower (p less than 0.05) in the heart failure groups (22 +/- 3 ms for medicated and 17 +/- 3 ms for nonmedicated) than in the transplant patients (41 +/- 5 ms) or control subjects (58 +/- 5 ms). Heart period variability of the transplant patients was less than that of the control patients (p less than 0.05). A stepwise regression model revealed that heart period variability was inversely related to systolic arterial pressure and directly related to time after transplantation (R2 = 0.39; p = 0.03) in the transplant patients. Baroreflex gain of normotensive transplant patients was normal (11.7 +/- 1.0 ms/mm Hg) and correlated directly with heart period variability (r = 0.62; p less than 0.001). These data suggest that subnormal levels of cardiac parasympathetic activity at rest associated with congestive heart failure can be restored progressively toward normal by correction of congestive heart failure after cardiac transplantation. Post-transplant hypertension opposes this correction of baseline parasympathetic activity.

These studies demonstrate that immune monitoring and individualized modulation of recipient immune reactivity using a quality-controlled preparation of rabbit antithymocyte globulin can improve results of cardiac transplantation. The most valuable assay in individualizing drug doses was the serial measurement of T-cell levels using a complete lymphocyte profile technique and monitoring with phytohemagglutinin to rule out false low T-cell levels. Using this system, the incidence and severity of early rejections were markedly reduced and no grafts were lost to rejection in the first month. The recent first-year graft survival has been about 60%, an improvement largely related to a reduction in early rejection and infection. This technique of immunosuppression appears quite promising for improving the results of future cardiac transplantations.