Thursday, February 24, 2011

Hybrid Procedure: Intraop. VSD closure

Catheterization and Cardiovascular Interventions 2011;77:557-563







A novel method of hybrid intraoperative catheter-based closure of ventricular septal defects using the Amplatzer® PDA occluder
Christian Neukamm MD, et al.

Oslo, Norway & Kiel, Germany

Background: In five patients, an apical muscular septal defect was closed in a hybrid approach using the Amplatzer® duct occluder during open heart surgery, whereas concomitant defects were treated surgically. In addition to their different heart defects that needed surgery, all had a muscular ventricular septal defect in the apex of the heart, poorly accessible for traditional, surgical approach. We describe the method and outcome in these patients.

Methods: The tip of a forceps was advanced from the left into the right ventricle through the ventricular septal defect. The delivery sheath was caught under visual control in the right ventricle and pulled back into the left ventricle. The disc was developed and pulled back until it was felt tugging at the septum. Then the core was developed. The end of the device was visible in the right ventricle and was secured with a Prolene® suture.

Results: The procedures were event-free. During early follow-up there were either no or only insignificant shunts in the region of the prior trabecular defects in four patients. The unsatisfactory result in the last patient was caused by inaccurate preoperative assessment.

Conclusion: The method seems valuable in patients in need of other intracardiac surgery.
© 2010 Wiley-Liss, Inc.

Tuesday, February 22, 2011

Remote Ischemic Preconditioning - Animal Study

Circulation. 2011;123:714-721
Full Text

Remote Ischemic Preconditioning Protects the Brain Against Injury After Hypothermic Circulatory Arrest

Hanna A. Jensen, MD, PhD*; et al.
Correspondence to Hanna Jensen, MD, Clinical Research Center, Oulu University Hospital, P.O. Box 5000, Oulu University 90014, Finland. E-mail hanna.alaoja.jensen@gmail.com

Background— Ischemic preconditioning (IPC) is a mechanism protecting tissues from injury during ischemia and reperfusion. Remote IPC (RIPC) can be elicited by applying brief periods of ischemia to tissues with ischemic tolerance, thus protecting vital organs more susceptible to ischemic damage. Using a porcine model, we determined whether RIPC of the limb is protective against brain injury caused by hypothermic circulatory arrest (HCA).

Methods and Results— Twelve piglets were randomized to control and RIPC groups. RIPC was induced in advance of cardiopulmonary bypass by 4 cycles of 5 minutes of ischemia of the hind limb. All animals underwent cardiopulmonary bypass followed by 60 minutes of HCA at 18°C. Brain metabolism and electroencephalographic activity were monitored for 8 hours after HCA. Assessment of neurological status was performed for a week postoperatively. Finally, brain tissue was harvested for histopathological analysis.

Study groups were balanced for baseline and intraoperative parameters. Brain lactate concentration was significantly lower (P<0.0001, ANOVA) and recovery of electroencephalographic activity faster (P<0.05, ANOVA) in the RIPC group. RIPC had a beneficial effect on neurological function during the 7-day follow-up (behavioral score; P<0.0001 versus control, ANOVA). Histopathological analysis demonstrated a significant reduction in cerebral injury in RIPC animals (injury score; mean [interquartile range]: control 5.8 [3.8 to 7.5] versus RIPC 1.5 [0.5 to 2.5], P<0.001, t test).

Conclusions— These data demonstrate that RIPC protects the brain against HCA-induced injury, resulting in accelerated recovery of neurological function. RIPC might be neuroprotective in patients undergoing surgery with HCA and improve long-term outcomes. Clinical trials to test this hypothesis are warranted.

Monday, February 21, 2011

ProBNP in newborn with PDA

Article
Arch Dis Child Fetal Neonatal Ed 2008'93:F257-F260.

49 infants were analyzed (median GA 30 wks, weight 1220g)
18 had hemodynamically-significant PDA - Day 3 NT-proBNP was high (median 32,907 pg/ml; Range: 11,396 - 127,155 pg/ml).
31 controls (no PDA, no Sepsis) - Day 3 median NT-pro-BNP was 3147 pg/ml (Range: 521 - 10,343 pg/ml).

Cut-off value for Day 3, NT-pro-BNP is 11,395 pg/ml for hemodynamically-significant PDA (Sensitivity 100% and Specificity 95%)

Sepsis: Day 10 NT-pro-BNP was elevated in infants who developed sepsis. Animal studies suggest that inflammatory cytokines may stimulate production and release of BNP during sepsis.

Wednesday, February 16, 2011

Hypertension with Dexmedetomidine

Genetic Variations in the α2A-Adrenoreceptor Are Associated with Blood Pressure Response to the Agonist Dexmedetomidine
Daniel Kurnik et al.

CIRC GENETICS.110.957662 Published online before print February 15, 2011​

Background—α2A-Adrenoceptors (α2AA-ARs) have important roles in sympathetic cardiovascular regulation. Variants of ADRA2A affect gene transcription and expression and are associated with insulin release and risk for type 2 diabetes. We examined whether ADRA2A variants are also associated with cardiovascular responses to the selective α2-AR-agonist, dexmedetomidine.

Methods and Results—73 healthy subjects participated in a placebo-controlled single-blind study. After 3 infusions of placebo, subjects received 3 incremental infusions of dexmedetomidine (cumulative dose, 0.4 mcg/kg). Primary outcomes were changes in systolic blood pressure (SBP) and plasma norepinephrine concentrations, measured as difference of the area-under-the-curve during placebo and dexmedetomidine infusions (ΔAUC). We used multiple linear regression analysis to examine the associations between 9 ADRA2A tagging variants and 5 inferred haplotypes and ΔAUC after adjustment for covariates. Homozygous carriers of rs553668, and the corresponding haplotype 4, previously associated with increased α2A-AR expression, had a 2.2-fold greater decrease in AUCSBP after dexmedetomidine (adjusted P=0.006); similarly, the maximum decrease in SBP was 24.7±8.1 mmHg compared to 13.6±5.9 mmHg in carriers of the wildtype allele (P=0.007). Carriers of haplotype 3, previously associated with reduced α2A-AR expression, had a 44% smaller decrease in AUCSBP (P=0.013). Haplotype information significantly improved the model predicting the decrease in SBP (P<0.001). There were similar but non-significant trends for diastolic blood pressure and heart rate. Genotypes were not significantly associated with norepinephrine responses.

Conclusions—Common ADRA2A variants are associated with the hypotensive response to dexmedetomidine. Effects of specific variants/haplotypes in vivo are compatible with their known effects on gene expression in vitro.

Tuesday, February 15, 2011

Hypothermia and Arrhythmogenesis

Enhanced Dispersion of Repolarization Explains Increased Arrhythmogenesis in Severe Versus Therapeutic Hypothermia

Joseph S. Piktel, MD, et al.

Circulation: Arrhythmia and Electrophysiology. 2011; 4: 79-86

From The Heart and Vascular Research Center, MetroHealth Campus, Case Western Reserve University, Cleveland, OH.

Background— Hypothermia is proarrhythmic, and, as the use of therapeutic hypothermia (TH) increases, it is critically important to understand the electrophysiological effects of hypothermia on cardiac myocytes and arrhythmia substrates. We tested the hypothesis that hypothermia-enhanced transmural dispersion of repolarization (DOR) is a mechanism of arrhythmogenesis in hypothermia. In addition, we investigated whether the degree of hypothermia, the rate of temperature change, and cooling versus rewarming would alter hypothermia-induced arrhythmia substrates.

Methods and Results— Optical action potentials were recorded from cells spanning the transmural wall of canine left ventricular wedge preparations at baseline (36°C), during cooling and during rewarming. Electrophysiological parameters were examined while varying the depth of hypothermia. On cooling to 26°C, DOR increased from 26±4 ms to 93±18 ms (P=0.021); conduction velocity decreased from 35±5 cm/s to 22±5 cm/s (P=0.010). On rewarming to 36°C, DOR remained prolonged, whereas conduction velocity returned to baseline. Conduction block and reentry was observed in all severe hypothermia preparations. Ventricular fibrillation/ventricular tachycardia was seen more during rewarming (4/5) versus cooling (2/6). In TH (n=7), cooling to 32°C mildly increased DOR (31±6 to 50±9, P=0.012), with return to baseline on rewarming and was associated with decreased arrhythmia susceptibility. Increased rate of cooling did not further enhance DOR or arrhythmogenesis.

Conclusions— Hypothermia amplifies DOR and is a mechanism for arrhythmogenesis. DOR is directly dependent on the depth of cooling and rewarming. This provides insight into the clinical observation of a low incidence of arrhythmias in TH and has implications for protocols for the clinical application of TH.

Tricuspid Valve Implantation in Fontan Patient

Circulation: Cardiovascular Interventions. 2011;4:112-3.
Images in Cardiology























History:
Tricuspid Atresia - type 1c
(Tricuspid atresia, Normally-related Great Arteries, VSD, no PS)

14 yrs: Fontan-Bjork Operation (RA-RV Hancock Prosthesis, Closure of ASD and VSD)

24 yrs: Obstruction of Hancock prosthesis. Therefore, replaced with 23 mm Aortic Homograft

38 yrs: Complete Heart Block - Dual Chamber pacemaker (RV lead via homograft)

45 yrs: PLE, failure of medical therapy, Severe TR

47 yrs: Melody Valve in Tricuspid position (inside Aortic Homograft). Resolution of PLE

14 mo follow-up: No recurrence of PLE.

Melody Valve in Branch PA in Tetralogy of Fallot with RV failure

Melody Valve Implantation Into the Branch Pulmonary Arteries for Treatment of Pulmonary Insufficiency in an Ovine Model of Right Ventricular Outflow Tract Dysfunction Following Tetralogy of Fallot Repair.

J. Daniel Robb, et al.

Circulation: Cardiovascular Interventions. 2011; 4: 80-87

Correspondence to Matthew J. Gillespie, MD, The Children's Hospital of Philadelphia, Room 6NE42, Main Building, 34th and Civic Center Blvd, Philadelphia, PA 19104. E-mail Gillespie@email.chop.edu

Background— Transannular patch (TAP) repair of tetralogy of Fallot often results in significant right ventricular outflow tract (RVOT) dilation and distortion. We hypothesized that insertion of Melody valves into the proximal right and left branch pulmonary arteries (PAs) would reduce pulmonary regurgitation fraction (PRF) in an ovine model of pulmonary insufficiency and dilated RVOT.

Methods and Results— Ten sheep underwent baseline cardiac catheterization, surgical pulmonary valvectomy, and TAP placement. A subset (n=5) had Melody valves (2 devices per animal) inserted into the proximal right and left PAs during the surgical procedure. Melody valves were placed distal to the right-upper-lobe (RUL) artery branch, leaving the RUL “unprotected.” Preoperative MRIs (n=5) were used to determine baseline RV ejection fraction (RVEF) and left ventricular (LV) EF. All surviving animals (n=9) underwent MRI and catheterization 6 weeks postsurgery.

Mean PRF was lower in the Melody valve group (15±6% versus 37±3%; P=0.014). The unprotected RUL was responsible for 64% of the PRF measured in the Melody valve group. In the non-Melody group, the RVEF was lower than baseline (P=0.003) and than in the Melody group (P=0.05). The LVEF was also lower in the non-Melody group versus baseline (P=0.004) and versus Melody (P=0.01).

Conclusions— Bilateral branch PA Melody valve implantation significantly reduced PRF and altered RV and LV function favorably in a model of TAP for tetralogy of Fallot. This novel intervention may offer potential benefit in treating patients with anatomically heterogeneous disease of the RVOT.

TGF-Beta pathway in Kawasaki Disease

Transforming Growth Factor-β Signaling Pathway in Patients With Kawasaki Disease
Chisato Shimizu, MD, at al.
Circulation: Cardiovascular Genetics. 2011; 4: 16-25

Background— Transforming growth factor (TGF)-β is a multifunctional peptide that is important in T-cell activation and cardiovascular remodeling, both of which are important features of Kawasaki disease (KD). We postulated that variation in TGF-β signaling might be important in KD susceptibility and disease outcome.

Methods and Results— We investigated genetic variation in 15 genes belonging to the TGF-β pathway in a total of 771 KD subjects of mainly European descent from the United States, the United Kingdom, Australia, and the Netherlands. We analyzed transcript abundance patterns using microarray and reverse transcriptase–polymerase chain reaction for these same genes, and measured TGF-β2 protein levels in plasma. Genetic variants in TGFB2, TGFBR2, and SMAD3 and their haplotypes were consistently and reproducibly associated with KD susceptibility, coronary artery aneurysm formation, aortic root dilatation, and intravenous immunoglobulin treatment response in different cohorts. A SMAD3 haplotype associated with KD susceptibility replicated in 2 independent cohorts and an intronic single nucleotide polymorphism in a separate haplotype block was also strongly associated (A/G, rs4776338) (P=0.000022; odds ratio, 1.50; 95% confidence interval, 1.25 to 1.81). Pathway analysis using all 15 genes further confirmed the importance of the TGF-β pathway in KD pathogenesis. Whole-blood transcript abundance for these genes and TGF-β2 plasma protein levels changed dynamically over the course of the illness.

Conclusions— These studies suggest that genetic variation in the TGF-β pathway influences KD susceptibility, disease outcome, and response to therapy, and that aortic root and coronary artery Z scores can be used for phenotype/genotype analyses. Analysis of transcript abundance and protein levels further support the importance of this pathway in KD pathogenesis.

Echo: Hypoplastic Left Heart Syndrome - RV function

J Am Coll Cardiol Img, 2011; 4:128-137
© 2011 by the American College of Cardiology Foundation

Novel Insights Into RV Adaptation and Function in Hypoplastic Left Heart Syndrome Between the First 2 Stages of Surgical Palliation
Nee Scze Khoo, MBChB*,*, Jeffrey F. Smallhorn, MD*, Sachie Kaneko, MD*, Kimberly Myers, MD*, Shelby Kutty, MD, Edythe B. Tham, MBBS*

Objectives: This study sought to examine the changes in ventricular function of hypoplastic left heart syndrome (HLHS) between the first 2 stages of surgical palliation.

Background: The mortality risk between first and second stages of surgical palliation in HLHS remains high. Right ventricular (RV) dysfunction predicts mortality. Postulated mechanisms include a maladaptive contraction pattern, myocardial ischemia, or contraction asynchrony. Speckle tracking imaging allows accurate measurement of myocardial deformation without geometric assumptions.

Methods: Prospective echocardiography pre-Norwood and pre-bidirectional cavopulmonary anastomosis (BCPA) examinations were performed in 20 HLHS patients, with comparisons made between stages. Measurements of ventricular function included: longitudinal/circumferential strain ratio, reflecting changes in contraction pattern; post-systolic strain index, a potential marker of myocardial ischemia; and mechanical dyssynchrony index. Relationships between echocardiographic variables and magnetic resonance imaging RV parameters before BCPA were examined.

Results: Before BCPA, myocardial contractility estimated by isovolumic acceleration and strain rate was reduced, paralleled by an increased in post-systolic strain index (p < 0.01). Right ventricular longitudinal/circumferential strain ratio decreased, becoming similar to a left ventricle–like contraction pattern, and this correlated with decreased mechanical dyssynchrony index (r = 0.65, p < 0.01), magnetic resonance imaging RV end-diastolic volume (r = 0.65, p < 0.05) and mass (r = 0.71, p < 0.01). Ventricular strain (r = –0.72, p < 0.01), strain rate (r = –0.85, p < 0.001), and mechanical dyssynchrony index (r = –0.73, p < 0.01) correlated linearly with magnetic resonance imaging–derived RV ejection fraction.

Conclusions: Reduced RV contractility occurred before BCPA. RV with a left ventricle–like contraction pattern was associated with improved contraction synchrony as well as a reduction in RV size and mass in HLHS. The finding of increased post-systolic strain index before BCPA is novel and its potential link with myocardial ischemia warrants further investigation. RV strain, strain rate, and contraction synchrony measured by speckle tracking imaging correlated closely with ventricular function and might be useful for monitoring ventricular function in HLHS.

Monday, February 14, 2011

Images: Raghib complex

Raghib complex:
Persistent LSVC to LA
Absent Coronary sinus (considered unroofed)
ASD at the inferior part of atrial septum
JACC 2022;57:e15 (Images in Cardiology)







EP: Risk Factors for Recurrent Syncope in LQTS (A negative Study?!)

J Am Coll Cardiol, 2011; 57:941-950

Risk Factors for Recurrent Syncope and Subsequent Fatal or Near-Fatal Events in Children and Adolescents With Long QT Syndrome

Judy F. Liu, MD et al. for International Long QT Syndrome Registry

Objectives: We aimed to identify risk factors for recurrent syncope in children and adolescents with congenital long QT syndrome (LQTS).

Background: Data regarding risk assessment in LQTS after the occurrence of the first syncope episode are limited.

Methods: The Prentice-Williams-Peterson conditional gap time model was used to identify risk factors for recurrent syncope from birth through age 20 years among 1,648 patients from the International Long QT Syndrome Registry.

Results: Multivariate analysis demonstrated that corrected QT interval (QTc) duration (500 ms) was a significant predictor of a first syncope episode (hazard ratio: 2.16), whereas QTc effect was attenuated when the end points of the second, third, and fourth syncope episodes were evaluated (hazard ratios: 1.29, 0.99, 0.90, respectively; p < 0.001 for the null hypothesis that all 4 hazard ratios are identical). A genotype-specific subanalysis showed that during childhood (0 to 12 years), males with LQTS type 1 had the highest rate of a first syncope episode (p = 0.001) but exhibited similar rates of subsequent events as other genotype-sex subsets (p = 0.63). In contrast, in the age range of 13 to 20 years, long QT syndrome type 2 females experienced the highest rate of both first and subsequent syncope events (p < 0.001 and p = 0.01, respectively). Patients who experienced 1 episodes of syncope had a 6- to 12-fold (p < 0.001 for all) increase in the risk of subsequent fatal/near-fatal events independently of QTc duration. Beta-blocker therapy was associated with a significant reduction in the risk of recurrent syncope and subsequent fatal/near-fatal events.

Conclusions: Children and adolescents who present after an episode of syncope should be considered to be at a high risk of the development of subsequent syncope episodes and fatal/near-fatal events regardless of QTc duration.

Saturday, February 12, 2011

Thrombocytopenia and Risk of IVH in neonates

Thrombocytopenia in neonates and the risk of intraventricular hemorrhage: a retrospective cohort study

Jeannette S. von Lindern email, Tjitske van den Bruele email, Enrico Lopriore email and Frans J. Walther email

BMC Pediatrics 2011, 11:16doi:10.1186/1471-2431-11-16

Published:11 February 2011

Abstract (provisional)

Background The overall prevalence of thrombocytopenia in neonates admitted to neonatal intensive care units ranges from 22 to 35%. There are only a few small studies that outline the relationship between the severity of thrombocytopenia and the risk of bleeding. This makes it difficult to form an evidence-based threshold for platelet transfusions in neonatal patients. The aim of this study was to determine the prevalence of thrombocytopenia in a tertiary neonatal intensive care unit and to study the relation between thrombocytopenia and the risk of intraventricular hemorrhage (IVH). Methods We performed a retrospective cohort study of all patients with thrombocytopenia admitted to our neonatal tertiary care nursery between January 2006 and December 2008. Patients were divided into 4 groups according to the severity of thrombocytopenia: mild (100-149x109/L), moderate (50-99x109/L), severe (30-49x109/L) or very severe (< p="0.3)." p="0.4)." p="0.7).">

Wednesday, February 9, 2011

Marfans Syndrome: Revised Ghent Criteria 2010

J Med Genet 2010;47:476-485

The revised Ghent nosology for the Marfan syndrome
Bart L. Loeys et al.

Abstract
The diagnosis of Marfan syndrome (MFS) relies on defined clinical criteria (Ghent nosology), outlined by international expert opinion to facilitate accurate recognition of this genetic aneurysm syndrome and to improve patient management and counselling. These Ghent criteria, comprising a set of major and minor manifestations in different body systems, have proven to work well since with improving molecular techniques, confirmation of the diagnosis is possible in over 95% of patients. However, concerns with the current nosology are that some of the diagnostic criteria have not been sufficiently validated, are not applicable in children or necessitate expensive and specialised investigations. The recognition of variable clinical expression and the recently extended differential diagnosis further confound accurate diagnostic decision making. Moreover, the diagnosis of MFS—whether or not established correctly—can be stigmatising, hamper career aspirations, restrict life insurance opportunities, and cause psychosocial burden. An international expert panel has established a revised Ghent nosology, which puts more weight on the cardiovascular manifestations and in which aortic root aneurysm and ectopia lentis are the cardinal clinical features. In the absence of any family history, the presence of these two manifestations is sufficient for the unequivocal diagnosis of MFS. In absence of either of these two, the presence of a bonafide FBN1 mutation or a combination of systemic manifestations is required. For the latter a new scoring system has been designed. In this revised nosology, FBN1 testing, although not mandatory, has greater weight in the diagnostic assessment. Special considerations are given to the diagnosis of MFS in children and alternative diagnoses in adults. We anticipate that these new guidelines may delay a definitive diagnosis of MFS but will decrease the risk of premature or misdiagnosis and facilitate worldwide discussion of risk and follow-up/management guidelines.

Tuesday, February 8, 2011

Perspective: Mentors

J Am Coll Cardiol, 2011; 57:885-886

EDITOR'S PAGE

Mentors

Anthony N. DeMaria, MD, Editor-in-Chief, Journal of the American College of Cardiology

It is the "fellowship mating" season, and our halls are filled with residents interviewing for our cardiology fellowship program. As part of the ritual, I am frequently consulted by our own medical residents as to what attributes they should look for in a training program and how they can select the best institution to prepare them for a productive career. My answer is getting increasingly simpler. Accepting the significance of a good patient mix, a large number of procedures, diverse and productive research laboratories, and so on, I am more than ever convinced that the most important ingredient to preparing a successful career is an excellent mentor. In my opinion, the ability to serve as a great mentor is one of the most underestimated and underappreciated skills in medicine.

An excellent mentor is important to those who plan to devote themselves primarily to the practice of clinical medicine. Perhaps better characterized as a "role model," an outstanding mentor can provide not only a comprehensive knowledge base and procedural skills, but also the sage clinical judgment that signifies the superior clinician. Perhaps of even greater importance, a mentor can convey a "philosophy of practice," including the optimal interaction with patients and physician colleagues, a regimen for remaining current with advances in the field, and a sound concept of how the practice of medicine fits into a full life. A supportive mentor can also provide guidance in selecting the best practice opportunity and can maintain a close relationship for many years.

As important as a good mentorship is to the clinician, it is even more critical to the success of the academician. In addition to conveying clinical prowess, the mentor must provide the investigative expertise that will enable a productive research career. Laboratory skills must be taught, as well as the investigative mindset to ask the right questions, design the appropriate protocols, and analyze the results correctly. Writing a manuscript that appropriately and convincingly presents the studies and findings must also be mastered. Mentoring an aspiring academician is a demanding task, and requires a skill set for the teacher over and above that required to be successful investigators themselves.

The expertise that must be transmitted by an accomplished mentor and mastered by an eager trainee is summarized very well in an American College of Cardiology Heart House course organized by Valentin Fuster, titled "How to Become a Cardiovascular Investigator." This highly praised symposium covers specific issues required to be a productive researcher in a broad spectrum of individual areas ranging from interventional cardiology to genomics and proteomics. Important lectures are devoted to obtaining grants, writing a paper, and finding a job. The key subject discussed, at least in my opinion, is how to choose a mentor; if you are successful at this task, the rest will be taken care of.

My own personal experience has been that a mentor can provide so much more than mere medical expertise. My mentor, Dean Mason, set a tone for how to navigate the often turbulent waters of academic medicine. He afforded opportunities within medicine that might never have been available otherwise, was a tireless cheerleader and encourager, and offered friendship and counsel outside of the professional setting. His many pithy sayings still often come to mind, such as "no one in a pissing contest stays dry." The affirmation of his influence was that I tried to imitate him as much as possible, especially in my own role as mentor.

Given the complexity and importance of being a great mentor, it has always been my impression that this talent is not adequately appreciated and celebrated. At awards selections (and presentations), at promotion meetings, and when screening potential recruits, a detailed recitation of the candidate's publications, grants, and administrative positions is often followed by only a brief (if any) mention of his or her successful trainees. Nevertheless, the impact that trainees have on medicine is often the greatest contribution that a mentor makes to the field. For me, many of the most satisfying moments I have experienced in my life have been in conjunction with the achievements of those I have had a hand in training.

It is clear that being a mentor is one of the most important functions in medicine. A good mentor is almost always crucial to the success of a trainee. Moreover, multiple skills are required to be an excellent mentor, and like most other talents, these are found in abundance in a relatively modest number of individuals. A mentor has to skillfully transmit not only codified medical expertise, but also a variety of intangibles that help to make the trainee a facile academician as well as a complete person. That this critically important function does not appear to be more highly valued and celebrated continues to astound me, but I intend to lobby for greater recognition. So, it is very easy for me to respond to a resident when asked what qualities to seek in a cardiology fellowship. I just tell them to go for the one with the best proven mentors.

EP: Short QT syndrome Criteria

Am Coll Cardiol, 2011; 57:802-812,

The Short QT Syndrome: Proposed Diagnostic Criteria

Michael H. Gollob, MD*,,*, Calum J. Redpath, MBChB, PhD and Jason D. Roberts, MD*

Objectives: We aimed to develop diagnostic criteria for the short QT syndrome (SQTS) to facilitate clinical evaluation of suspected cases.

Background: The SQTS is a cardiac channelopathy associated with atrial fibrillation and sudden cardiac death. Ten years after its original description, a consensus regarding an appropriate QT interval cutoff and specific diagnostic criteria have yet to be established.

Methods: The MEDLINE database was searched for all reported cases of SQTS in the English language, and all relevant data were extracted. The distribution of QT intervals and electrocardiographic (ECG) features in affected cases were analyzed and compared to data derived from ECG analysis from general population studies.

Results: A total of 61 reported cases of SQTS were identified. Index events, including sudden cardiac death, aborted cardiac arrest, syncope, and/or atrial fibrillation occurred in 35 of 61 (57.4%) cases. The cohort was predominantly male (75.4%) and had a mean QTc value of 306.7 ms with values ranging from 248 to 381 ms in symptomatic cases. In reference to the ECG characteristics of the general population, and in consideration of clinical presentation, family history, and genetic findings, a highly sensitive diagnostic scoring system was developed.

Conclusions: Based on a comprehensive review of 61 reported cases of the SQTS, formal diagnostic criteria have been proposed that will facilitate diagnostic evaluation in suspected cases of SQTS. Diagnostic criteria may lead to a greater recognition of this condition and provoke screening of at-risk family members.

Genetics Primer for Primary Cardiologist

Circulation. 2011;123:544-550

Genetics Primer for the General Cardiologist. Impact of Genetic Insights Into Mendelian Disease on Cardiovascular Clinical Practice

Luke Kim, MD; Richard B. Devereux, MD; Craig T. Basson, MD, PhD

An extract of the first 250 words of the full text is provided, because this article has no abstract.

Introduction: Recent advances in the field of genetics have significantly enhanced our understanding of many cardiovascular conditions and improved diagnosis as well as management of these disorders. However, mendelian cardiovascular diseases still pose unique challenges to clinicians, especially when presented with inherited conditions that have a wide range of phenotypic presentations. In cardiovascular single-gene disorders with potentially devastating initial manifestations, such as sudden cardiac death (SCD) or aortic dissection, appropriate and prompt identification of individuals at risk is imperative. In addition, the management of the disease is not only applicable to the individuals at risk but also extends to other members in the family. Therefore, the general approach to patients with such diseases and their affected family members needs to be considered in the context of fundamental principles of mendelian inheritance. Numerous examples of cardiovascular mendelian disorders exist in which the importance of genetics has been clearly recognized, and most common monogenic cardiovascular disorders are transmitted in families in an autosomal dominant fashion. In such autosomal dominant disorders, it is important to remember the overriding principle that any first-degree relative of an individual with an autosomal dominant multigenerational familial cardiovascular disorder has a 50% chance of also being affected by this genetic trait. Thus, when added to a family history, any symptom or sign on history, clinical evaluation, or testing that is consistent with the diagnosis in question creates a >50% likelihood that the family member is affected by the disorder as well. In this review, we will focus on a . . . [Full Text of this Article]

Thursday, February 3, 2011

Bicuspid Aortic Valve: Two developmentally-distinct types!

J Am Coll Cardiol, 2009; 54:2312-2318

Bicuspid Aortic Valves With Different Spatial Orientations of the Leaflets Are Distinct Etiological Entities

Borja Fernández, PhD*,*, Ana C. Durán, PhD*, Teresa Fernández-Gallego, BSc*, M. Carmen Fernández, BSc*, Miguel Such, MD, Josep M. Arqué, MD and Valentín Sans-Coma, PhD*
* Department of Animal Biology, Faculty of Science, University of Málaga, Málaga, Spain Department of Cardiovascular Surgery, University Hospital Virgen de la Victoria, Málaga, Spain Department of Cardiovascular Surgery, University Hospital Carlos Haya, Málaga, Spain

Objectives: The aim of this study was to decide whether bicuspid aortic valves (BAVs) with fused right and noncoronary leaflets (R-N) and BAVs with fused right and left leaflets (R-L) have different etiologies or are the product of a single diathesis.

Background: The BAV is the most common congenital cardiac malformation. The R-N and R-L BAVs are the most frequent BAV subtypes.

Methods: The study was carried out in adult and embryonic hearts of endothelium nitric oxide synthase knock-out mice and inbred Syrian hamsters with a high incidence of R-N and R-L BAVs, respectively. The techniques used were histochemistry, immunohistochemistry, and scanning electron microscopy.

Results: The R-N BAVs result from a defective development of the cardiac outflow tract (OT) endocardial cushions that generates a morphologically anomalous right leaflet. The left leaflet develops normally ("Vertical Orifice" seen in PSSAx echo view). The R-L BAVs are the outcome of an extrafusion of the septal and parietal OT ridges that thereby engenders a sole anterior leaflet. The noncoronary leaflet forms normally ("Horizontal Orifice" seen in PSSAx echo view...more common).

Conclusions: The R-N and R-L BAVs are different etiological entities. The R-N BAVs are the product of a morphogenetic defect that happens before the OT septation and that probably relies on an exacerbated nitric oxide–dependent epithelial-to-mesenchymal transformation. The R-L BAVs result from the anomalous septation of the proximal portion of the OT, likely caused by a distorted behavior of neural crest cells. Care should be taken in further work on BAV genetics because R-N and R-L BAVs might rely on different genotypes. Detailed screening for R-N and R-L BAVs should be performed for a better understanding of the relationships between these BAV morphologic phenotypes and other heart disease.

More postings on this subject

Tuesday, February 1, 2011

Cath Lab: Percutaneous Pulmonary Valve Implantation - Early and Late Functional Outcome

J Am Coll Cardiol, 2011; 57:724-731

Early Versus Late Functional Outcome After Successful Percutaneous Pulmonary Valve Implantation. Are the Acute Effects of Altered Right Ventricular Loading All We Can Expect?

Philipp Lurz, MD*,,,*, Johannes Nordmeyer, MD*,,, Alessandro Giardini, MD, PhD, Sachin Khambadkone, MD, Vivek Muthurangu, MD*, Silvia Schievano, PhD*, Jean-Benoit Thambo, MD,, Fiona Walker¶, Seamus Cullen¶, Graham Derrick, Andrew M. Taylor, MD*, and Philipp Bonhoeffer, MD*

Objectives: The purpose of this study was to assess the potential of late positive functional remodeling after percutaneous pulmonary valve implantation (PPVI) in right ventricular outflow tract dysfunction.

Background: PPVI has been shown to impact acutely on biventricular function and exercise performance, but the potential for further late functional remodeling remains unknown.
Methods: Sixty-five patients with sustained hemodynamic effects of PPVI at 1 year were included. Patients were divided into 2 subgroups based on pre-procedural predominant pulmonary stenosis (PS) (n = 35) or predominant pulmonary regurgitation (PR) (n = 30). Data from magnetic resonance imaging and cardiopulmonary exercise testing were compared at 3 time points: before PPVI, within 1 month (early) and at 12 months (late) after PPVI.

Results: There was a significant decrease in right ventricle end-diastolic volume early after PPVI in both subgroups of patients. Right ventricle ejection fraction improved early only in the PS group (51 ± 11% vs. 58 ± 11% and 51 ± 12% vs. 50 ± 11%, p < 0.001 for PS, p = 0.13 for PR). Late after intervention, there were no further changes in magnetic resonance parameters in either group (right ventricle ejection fraction, 58 ± 11% in the PS group and 52 ± 11% in the PR group, p = 1.00 and p = 0.13, respectively). In the PS group at cardiopulmonary exercise testing, there was a significant improvement in peak oxygen uptake early (24 ± 8 ml/kg/min vs. 27 ± 9 ml/kg/min, p = 0.008), with no further significant change late (27 ± 9 ml/kg/min, p = 1.00). In the PR group, no significant changes in peak oxygen uptake from early to late could be demonstrated (25 ± 8 ml/kg/min vs. 25 ± 8 ml/kg/min vs. 26 ± 9 ml/kg/min, p = 0.48).

Conclusions: In patients with a sustained hemodynamic result 1 year after PPVI, a prolonged phase of maintained cardiac function is observed. However, there is no evidence for further positive functional remodeling beyond the acute effects of PPVI