Cardiac Valve Disorders Research Articles

Mitral Stenosis Berat pada Penyakit Jantung Rematik

Rheumatic Heart Disease (RHD) has high morbidity and mortality. Cardiac valve disorders after rheumatic fever are the leading cause of heart failure in children and young adults. A comprehensive understanding of RHD can help early diagnosis and provide optimal management in the future. It has been reported that a 55-year-old man came to the heart clinic of Bhayangkara Hospital Denpasar for routine control of heart disease. The patient has been diagnosed with rheumatic heart disease since 2018. The patient complains of shortness of breath when walking long distances and doing strenuous activities. The patient was diagnosed with CHF FC II ec RHD + MS moderate-severe (Wilkins score 8) + AF NVR (CHA2DS2VASc 3) and treated with heart failure and antiplatelet medication. Mitral stenosis due to RHD produces the typical pathological features seen in Transthoracic echocardiography (TTE), including fibrous thickening and calcification of the valve leaflets, fusion of the commissures, and thickening and shortening of chordae tendineae. Chronic stress overload on the LA due to MS can cause LA dilatation and trigger AF. RHD patients with AF are recommended for anticoagulation for stroke prevention. Patients with acute rheumatic fever clinical features should be evaluated further and given long-term therapy to prevent more severe heart problems.Keywords: atrial fibrillation, mitral stenosis, rheumatic heart disease

Impact of Catheter Ablation on Mitral Regurgitation and Atrial Fibrillation: A Case Study

Mitral regurgitation is recognized as the most common valvulopathy among cardiac valve disorders, with causes divided into primary and secondary components. Traditionally, the secondary component has been associated with the dilation of the ventricular cavity and ring; however, recent interpretations also include the dilation of the left atrium as a significant factor, especially when the dimensions of the left ventricular cavity are preserved. This new perspective has led to a reinterpretation of the pathogenesis, diagnosis, and treatment of atrial functional mitral regurgitation. The research focused on a case study of patients with this condition and atrial fibrillation, who were treated through catheter ablation. This approach was supported by an exhaustive bibliographic review conducted in databases such as MEDLINE via PUBMED. The findings reveal that atrial functional mitral regurgitation, now recognized as a distinct pathological entity, challenges the previous belief that only the dilation of the left ventricle and mitral ring were the causes of the disease. Furthermore, it was determined that catheter ablation is effective not only for restoring sinus rhythm but also for improving valvular function and quality of life in patients with this condition and atrial fibrillation

Cardiac arrhythmias associated with immune checkpoint inhibitors: A comprehensive disproportionality analysis of the FDA adverse event reporting system.

Introduction: With the widespread application of Immune checkpoint inhibitors (ICIs), it is important to explore the association between ICIs and cardiac arrhythmias and to characterize the clinical features of ICI-associated cardiac arrhythmias in real-world studies. Objective: The purpose of this study was to characterize the main features of ICI-related cardiac arrhythmias. Methods: From January 2017 to June 2021, data in the Food and Drug Administration Adverse Event Reporting System (FAERS) database were retrieved to conduct the disproportionality analysis. For the ICI-related cardiac arrhythmia detection, signals were detected by reporting odds ratio (ROR) and information component (IC), calculated using two-by-two contingency tables The clinical characteristics of patients reported with ICI-related cardiac arrhythmias were compared between fatal and non-fatal groups, and the time to onset (TTO) following different ICI regimens was further investigated. Multivariate logistic regression was used to evaluate the association between concurrent cardiotoxicities and ICI-associated arrhythmias. Results: We identified a total of 1957 ICI-associated cardiac arrhythmias reports which appeared to influence more men (64.44%) than women (30.76%), with a median age of 68 [interquartile range (IQR) 60-75] years. Cardiac arrhythmias were reported most often in patients with lung, pleura, thymus and heart cancers (38.02% of 1957 patients). Compared with the full database, ICIs were detected with pharmacovigilance of cardiac arrhythmias (ROR025 = 1.16, IC025 = 0.19). Anti-PD-1 and anti-PD-L1 monotherapies were found to be related to higher reporting of arrhythmias, corresponding to ROR025 = 1.03, IC025 = 0.06 and ROR025 = 1.27, IC025 = 0.29, respectively, with the exception of anti-CTLA-4 monotherapies (ROR025 = 0.57, IC025 = -1.21). The spectrum of arrhythmias induced by ICIs differed among therapeutic regimens. There was no significant difference in the onset time between monotherapy and combination regimen. Moreover, reports of ICI-associated arrhythmias were associated with other concurrent cardiotoxicity, including cardiac failure [ROR 2.61 (2.20-3.09)], coronary artery disorders [ROR 2.28 (1.83-2.85)], myocardial disorders [ROR 5.25 (4.44-6.22)], pericardial disorders [ROR 2.76 (2.09-3.64)] and cardiac valve disorders [ROR 3.21 (1.34-7.68)]. Conclusion: ICI monotherapy and combination therapy can lead to cardiac arrhythmias that can result in serious outcomes and tend to occur early. Our findings underscore the importance of early recognition and management of ICI-related cardiac arrhythmias.

Classification of heart sounds associated with murmur for diagnosis of cardiac valve disorders

Background: Nowadays, cardiovascular diseases have been a major cause of death in the world. The heart sound is still used as a primary tool for screening and diagnosing many pathological conditions of the human heart. The abnormality in the heart sounds starts appearing much earlier than the symptoms of the disease.

A change of heart: new roles for cilia in cardiac development and disease.

Although cardiac abnormalities have been observed in a growing class of human disorders caused by defective primary cilia, the function of cilia in the heart remains an underexplored area. The primary function of cilia in the heart was long thought to be restricted to left-right axis patterning during embryogenesis. However, new findings have revealed broad roles for cilia in congenital heart disease, valvulogenesis, myocardial fibrosis and regeneration, and mechanosensation. In this Review, we describe advances in our understanding of the mechanisms by which cilia function contributes to cardiac left-right axis development and discuss the latest findings that highlight a broader role for cilia in cardiac development. Specifically, we examine the growing line of evidence connecting cilia function to the pathogenesis of congenital heart disease. Furthermore, we also highlight research from the past 10 years demonstrating the role of cilia function in common cardiac valve disorders, including mitral valve prolapse and aortic valve disease, and describe findings that implicate cardiac cilia in mechanosensation potentially linking haemodynamic and contractile forces with genetic regulation of cardiac development and function. Finally, given the presence of cilia on cardiac fibroblasts, we also explore the potential role of cilia in fibrotic growth and summarize the evidence implicating cardiac cilia in heart regeneration.

Mechanical effects of ranolazine on normal and diabetic-isolated rat heart

Background and purpose:Diabetic cardiomyopathy is a complication of diabetes defined as cardiac dysfunction without the involvement of pericardial vessels, hypertension, or cardiac valve disorders. Ranolazine, an antianginal drug, acts through blocking of cardiac late sodium channels and/or inhibiting beta-oxidation of fatty acids. With regard to its mechanism of action, the present work has been carried out to investigate the potential useful effects of ranolazine on the systolic and diastolic dysfunctions in an experimental rat model of diabetic cardiomyopathy. Lidocaine, as a sodium channel blocker, was used to have a clearer image of the involved mechanisms.Experimental approach:Diabetes was induced by streptozocin. After 8 weeks, the effects of cumulative concentrations of ranolazine and lidocaine were evaluated on diabetic and normal hearts by the Langendorff method. Finally, the hearts were isolated from the Langendorff system and adenosine three phosphates (ATP) and adenosine diphosphate (ADP) concentrations were measured to assay the metabolic effect of ranolazine.Findings/Results:Ranolazine significantly decreased the velocity of systolic contraction (+dP/dt) and the velocity of diastolic relaxation (-dP/dt) and developed pressure in normal and diabetic rat hearts. However, this negative effect was greater in normal hearts compared to diabetics. Ranolazine (100 μM) decreased the ATP level only in normal hearts and the ATP/ADP ratio decreased significantly (P < 0.05) in both groups. This reduction was more prominent in normal hearts.Conclusion and implications:It is concluded that in the isolated rat heart preparation, ranolazine has no benefit on diabetic cardiomyopathy and may even worsen it. It seems that these effects are related to the metabolic effects of ranolazine.

The effect of in-hospital physiotherapy on handgrip strength and physical activity levels after cardiac valve surgery: a randomized controlled trial.

Patients who undergo cardiac valve surgery undertake routine physical therapy program. Despite its routine use, its influence on physical activity level post- surgery has not been illustrated. This study was to investigate whether 5 days of in-hospital physiotherapy could improve physical activity levels after cardiac valve surgery. The study is a single-blind randomized controlled trial which performed in Cardiothoracic Surgery Department. Patients who underwent cardiac valve surgery (n=34) for confirmed cardiac valve disorders were assessed during hospitalization. The intervention group received a daily post-operative physiotherapy intervention, consisting of individualized mobilization, breathing exercises, ambulation with or without a walking aid. There was no physiotherapy treatment in the control group. Measurements: physical activity was assessed with the handgrip strength test and the timed up and go test. The treatment group showed significantly greater handgrip strength [20.58 (7.17) vs. 12.96 (4.65) kg] and less time on the timed up and go test [5.92 (2.91) vs. 6.53 (1.60) s] compared to the control group on the 5th post-operative day. Whilst there was no significant difference on the timed up and go test between the 2 groups, handgrip strength on the 5th post-operative day was significantly different between the 2 groups. Patients who received physiotherapy during hospitalization showed increased levels of handgrip strength and physical activity on the 5th day after cardiac valve surgery compared to the control group. The clinical value of increased levels of physical activity after in-hospital physiotherapy following cardiac valve surgery requires further investigation.

The packet wavelet transform in the analysis of phonocardiogram's signals (aortic stenosis and mitral stenosis)

Heart murmurs are the first signs of cardiac valve disorders. Indeed, heart auscultation through a stethoscope has been recognised for a long time as an important tool for the diagnosis of heart disease. But, it remains insufficient for an efficient treatment of cardiovascular pathologies. The efficiency and accuracy of diagnosis can be improved considerably by using digital signal processing techniques to analyse the phonocardiographic (PCG) signals. The wavelet packet transforms (WPT) was successfully used as a feature to distinguish different heart sounds. It is introduced to analyse and identify the phonocardiogram's signals. The importance of application of the wavelet packet transform (WPT) to analyse the pathological severity of the aortic stenosis 'AS' and mitral stenosis 'MS' was presented. Then, the calculation of various parameters was performed for each patient.

The packet wavelet transform in the analysis of phonocardiogram's signals (aortic stenosis and mitral stenosis)

Heart murmurs are the first signs of cardiac valve disorders. Indeed, heart auscultation through a stethoscope has been recognised for a long time as an important tool for the diagnosis of heart disease. But, it remains insufficient for an efficient treatment of cardiovascular pathologies. The efficiency and accuracy of diagnosis can be improved considerably by using digital signal processing techniques to analyse the phonocardiographic (PCG) signals. The wavelet packet transforms (WPT) was successfully used as a feature to distinguish different heart sounds. It is introduced to analyse and identify the phonocardiogram's signals. The importance of application of the wavelet packet transform (WPT) to analyse the pathological severity of the aortic stenosis 'AS' and mitral stenosis 'MS' was presented. Then, the calculation of various parameters was performed for each patient.

Contemporary Burden of Atrial Fibrillation and Associated Mortality in Northeastern Italy

Based on different estimation methods, mortality attributable to atrial fibrillation (AF) has been demonstrated to increase over time in developed countries, reaching a share ranging from 1% to 5% of overall deaths. To assess the whole burden of AF-associated mortality, all diseases mentioned in death certificates of subjects aged ≥45years resident in the Veneto Region (Northeastern Italy) were analyzed for the 2008 to 2013 period. The prevalence of common chronic co-morbidities was compared between deaths with mention of AF and a sample of age-matched deaths without reported AF. The disease was mentioned among conditions contributing to death in 25,834 subjects, corresponding to 9.8% of all regional deaths. Rates of AF-associated mortality were higher in men and increased steeply with age, being above 1 per 100 among residents aged ≥85years. Compared with non-AF-associated deaths, the strongest associations were observed between AF and hypertensive diseases (prevalence ratio 1.62, 95% CI 1.57 to 1.67), cardiac valve disorders (2.43, 2.25 to 2.61), cardiomyopathies (1.93, 1.70 to 2.19), cerebrovascular diseases (1.55, 1.50 to 1.60), and chronic obstructive pulmonary disease (1.49, 1.42 to 1.57). AF-associated mortality resulted higher than previously reported, probably due to aging of the population with multiple predisposing diseases, an increased recognition of AF among the elderly, and a raised awareness of certifying physicians about the importance of AF. Analyses of all diseases mentioned in death certificates underscored the interaction of AF with several other circulatory and respiratory disorders in pathologic networks leading to an increased risk of death.

Risk of cardiac valvulopathy with use of bisphosphonates: a population-based, multi-country case-control study.

SummaryAnalyses of healthcare data from 30 million individuals in three countries showed that current use of bisphosphonates may be associated with a small increased risk of cardiac valvulopathy (vs. those not exposed within the previous year), although confounding cannot be entirely ruled out. The observed tendency for decreased valvulopathy risk with cumulative duration of bisphosphonate use >6 months may even indicate a protective effect with prolonged use. Further studies are still needed to evaluate whether bisphosphonates increase or decrease the risk of valvulopathy.IntroductionA signal of cardiac valve disorders with use of bisphosphonates was identified in the literature and EudraVigilance database, which contains reports of suspected adverse drug reactions from worldwide sources. The aim of this study was to evaluate the association using population-based healthcare data.MethodsThis was a case-control study among users of bisphosphonates and other drugs for osteoporosis in six healthcare databases covering over 30 million individuals in Italy, Netherlands and the UK from 1996 to 2012. Prescriptions/dispensations were used to assess drug exposure. Newly diagnosed cases of cardiac valvulopathy were identified via disease codes/free-text search. Controls were matched to each case by age, sex, database and index date. Adjusted odds ratios (ORs) were estimated using conditional logistic regression for the pooled data and meta-analysis of individual database risk estimates.ResultsA small but statistically significant association was found between exposure to bisphosphonates as a class and risk of valvulopathy. Overall risk was 18 % higher (95 % CI 12–23 %) in those currently exposed to any bisphosphonate (mainly alendronate and risedronate) vs. those not exposed within the previous year. Risk of valve regurgitation was 14 % higher (95 % CI 7–22 %). Decreased valvulopathy risk was observed with longer cumulative duration of bisphosphonate use, compared to use of less than 6 months. Meta-analyses of database-specific estimates confirmed results from pooled analyses.ConclusionsThe observed increased risks of cardiac valvulopathy with bisphosphonate use, although statistically significant, were quite small and unlikely to be clinically significant. Further studies are still needed to evaluate whether bisphosphonates increase or decrease the risk of valvulopathy and to investigate possible mechanisms for the association.Electronic supplementary materialThe online version of this article (doi:10.1007/s00198-015-3441-2) contains supplementary material, which is available to authorized users.

PMS1 - Treatment With Some Bisphosphonates Is Associated With Aortic and Mitral Valve Calcification

A signal of bisphosphonate-related cardiac valve calcification leading to cardiac valve insufficiency was detected in the European adverse event monitoring system (EudraVigilance); however no signal detection activity was conducted in the US. This pharmacovigilance analysis investigates and relationship between bisphosphonates and aortic and mitral valve calcification in the FDA Adverse Event Reporting System (FAERS). Bisphosphonate-related adverse event reports submitted to FAERS between 1997 and 2013 were used to investigate the disproportional reporting of cardiac valve disorders (CVD) in relation to bisphosphonates therapy, including aortic and mitral valve calcification. Multi-item Gamma Poisson Shrinker data mining algorithm was used to calculate Empirical Bayes Geometric Mean (EBGM) and corresponding 95% confidence interval as disproportionality measures. Signals that warrant further review are defined as measures with confidence interval lower limit≥2.0. The Anatomical Chemical and Therapeutic classification was used to define bisphosphonate exposure, and the Medical Dictionary for Regulatory Activities, Preferred Term coding hierarchy was used to define cardiac valve calcification. A total of 2,010 CVD events were submitted for bisphosphonates. Of those, 116 events were for cardiac valve calcification, affecting aortic valve (n=32); mitral valve (n=83); and pulmonary valve (n=1). Signals were detected for alendronate (aortic: n=8, EBGM=3.7, 95%CI=2.03-6.34; mitral: n=15, EBGM=3.99, 95%CI=2.58-5.96); pamidronate (aortic: n=7, EBGM=9.94, 95%CI=3.27-30.3; mitral: n=25, EBGM=36.8, 95%CI=26.1-50.6); and Zoledronate (aortic: n=13, EBGM=4.44, 95%CI=2.77-6.86; mitral: n=39, EBGM=7.23, 95%CI=5.45-9.58). No signal was detected for ibadronate (aortic: n=1, EBGM=0.92, 95%CI=0.21-2.92; mitral: n=2, EBGM=1.02, 95%CI=0.32-2.58) and risedronate (aortic: n=3, EBGM=2.6, 95%CI=0.99-5.9; mitral: n=2, EBGM=1.43, 95%CI=0.45-3.61; pulmonary: n=1, EBGM=1.36, 95%CI=0.3-4.38). Treatment with some bisphosphonates might be associated with aortic and mitral valve calcification. It might be necessary for prescribers to monitor patients for CVD before and periodically during bisphosphonates therapy. Signal clarification and evaluation activities by pharmacoepidemiologic studies are recommended.

Risk of new-onset atrial fibrillation in elderly patients with the overlap syndrome: a retrospective cohort study.

ObjectiveCo-existence of obstructive sleep apnea (OSA) and chronic obstructive pulmonary disease (COPD) is referred to as overlap syndrome. Overlap patients have greater degree of hypoxia and pulmonary hypertension than patients with OSA or COPD alone. Studies showed that elderly patients with OSA alone do not have increased risk of atrial fibrillation (AF) but it is not known if overlap patients have higher risk of AF. To determine whether elderly patients with overlap syndrome have an increased risk of AF.MethodsIn this single center, community-based retrospective cohort analysis, data were collected on 2,873 patients > 65 years of age without AF, presenting in the year 2006. Patients were divided into OSA group (n = 60), COPD group (n = 416), overlap syndrome group (n = 28) and group with no OSA or COPD (n = 2369). The primary endpoint was incidence of new-onset AF over the following two years. Logistic regression was performed to adjust for heart failure (HF), coronary artery disease, hypertension (HTN), cerebrovascular disease, cardiac valve disorders, diabetes mellitus, hyperlipidemia, chronic kidney disease (CKD) and obesity.ResultsThe incidence of AF was 10% in COPD group, 6% in OSA group and 21% in overlap syndrome group (P < 0.05). After adjusting for age, sex, HF, CKD, and HTN, patients with overlap syndrome demonstrated a significant association with new-onset AF (OR = 3.66, P = 0.007). HF, CKD and HTN were also significantly associated with new-onset AF (P < 0.05).ConclusionAmong elderly patients, the presence of overlap syndrome is associated with a marked increase in risk of new-onset AF as compared to the presence of OSA or COPD alone.

Wavelet packet entropy for heart murmurs classification.

Heart murmurs are the first signs of cardiac valve disorders. Several studies have been conducted in recent years to automatically differentiate normal heart sounds, from heart sounds with murmurs using various types of audio features. Entropy was successfully used as a feature to distinguish different heart sounds. In this paper, new entropy was introduced to analyze heart sounds and the feasibility of using this entropy in classification of five types of heart sounds and murmurs was shown. The entropy was previously introduced to analyze mammograms. Four common murmurs were considered including aortic regurgitation, mitral regurgitation, aortic stenosis, and mitral stenosis. Wavelet packet transform was employed for heart sound analysis, and the entropy was calculated for deriving feature vectors. Five types of classification were performed to evaluate the discriminatory power of the generated features. The best results were achieved by BayesNet with 96.94% accuracy. The promising results substantiate the effectiveness of the proposed wavelet packet entropy for heart sounds classification.

Heart sound reproduction based on neural network classification of cardiac valve disorders using wavelet transforms of PCG signals

Cardiac auscultatory proficiency of physicians is crucial for accurate diagnosis of many heart diseases. Plenty of diverse abnormal heart sounds with identical main specifications and different details representing the ambient noise are indispensably needed to train, assess and improve the skills of medical students in recognizing and distinguishing the primary symptoms of the cardiac diseases. This paper proposes a versatile multiresolution wavelet-based algorithm to first extract the main statistical characteristics of three well-known heart valve disorders, namely the aortic insufficiency, the aortic stenosis, and the pulmonary stenosis sounds as well as the normal ones. An artificial neural network (ANN) and statistical classifier are then applied alternatively to choose proper exclusive features. Both classification approaches suggest using Daubechies wavelet filter with four vanishing moments within five decomposition levels for the most prominent distinction of the diseases. The proffered ANN is a multilayer perceptron structure with one hidden layer trained by a back-propagation algorithm (MLP–BP) and it elevates the percentage classification accuracy to 94.42. Ultimately, the corresponding main features are manipulated in wavelet domain so as to sequentially regenerate the individual counterparts of the underlying signals.

Abstract 3407: The Transcriptional Mediator Complex Is Essential For Cardiac Valve Formation

The genetic causes of congenital heart diseases especially cardiac valve disorders are mostly unknown. During the last decade, the zebrafish became an excellent and established model organism (1) to uncover these genetic defects and (2) to elucidate the underlying molecular pathomechanisms. We recently isolated the zebrafish mutation ping pong ( png m683 ) in a large-scale ENU-mutagenesis screen for recessive lethal mutations that perturb cardiac function. png mutant zebrafish embryos show pathologically developed cardiac valves. Due to malformation of the cardiac AV valves, png mutant zebrafish embryos exhibit vigorous regurgitation of blood between the atrium and the ventricle. Furthermore, as a result of the cardiac valve malformation and cardiac dysfunction png mutants die at day 6 post fertilization. Expression of several factors known to be crucial for the proper development and formation of the atrio-ventricluar canal (e.g. notch1b, bmp4 or versican) is significantly altered in png mutant zebrafish hearts. By a positional cloning approach we demonstrate that the ping pong phenotype is caused by a promotor mutation in a zebrafish gene encoding for a novel component of the “transcriptional mediator complex”. This mediator complex is a multi-protein complex that acts as a transcriptional coactivator and transduces informations from transcription factors to the RNA polymerase II. png is strongly expressed in zebrafish as well as human cardiomyocytes. Furthermore, sequence alignments demonstrate the evolutionary conservation of the ping pong gene product. Gene specific knock-down studies by means of modified antisense oligonucleotides reveal a phenocopy of the png mutant phenotype whereas injection of the gene-specific mRNA in png mutant embryos restores the mutant phenotype indicating that png is indeed responsible for the observed phenotype. The zebrafish evolved as an excellent model organism to study the molecular signalling pathways involved in cardiac valve formation. By detailed characterization of the zebrafish line ping pong we will obtain new insights into these molecular mechanisms especially the transcriptional control of valve formation and therefore the pathomechanisms of human cardiac valve disorders.

Cabergoline and the risk of valvular lesions in endocrine disease.

The cardiac valvular risk associated with lower exposure to cabergoline in common endocrine conditions such as hyperprolactinemia is unknown. We performed a cross-sectional, case-control echocardiographic study to assess the valvular status in 102 subjects receiving cabergoline for endocrine disorders and 51 matched control subjects. Cabergoline treatment ranged from 12 to 228 months, with a cumulative dose of 18-1718 mg. Valvular regurgitation was equally prevalent in both groups and was almost exclusively mild. Two cabergoline-treated subjects had moderate mitral regurgitation; there was no relationship between cabergoline dose and the presence or severity of mitral valve regurgitation (P=NS). Mitral valve tenting area was significantly greater in the cabergoline group when compared with the control subjects (P=0.03). Mitral valve leaflet thickening was observed in 5.9% of cabergoline-treated subjects; no relationship with the cumulative cabergoline dose was found. No patient had aortic or tricuspid valvular restriction. No significantly increased risk of clinically relevant cardiac valve disorders was found in subjects treated with long-term cabergoline therapy at the doses used in endocrine practice. While exposure to cabergoline appears to be safe during low-dose long-term therapy, an association with subclinical changes in mitral valve geometry cannot be completely excluded.

Fifty years of open-heart surgery.

On May 6th, 2003, we celebrate the 50th anniversary of the first successful open-heart operation performed with the use of the heart-lung machine, one of the most important forms of therapy in the history of cardiac disease. On that spring day in Philadelphia, John H. Gibbon, Jr, MD, of the Jefferson University Medical Center, using total cardiopulmonary bypass for 26 minutes, closed a large secundum atrial septal defect in an 18-year-old woman. Beginning with this case, generations of cardiac surgeons have been able to operate on millions of human hearts with alacrity, efficiency, and consistency to correct complicated congenital heart defects, cardiac valve disorders in the young and old, atherosclerotic coronary artery obstructions, and large aneurysms of the thoracic aorta. Until 1953, cardiac surgery was in its infancy and was more of a curiosity, except for treatment of rheumatic mitral stenosis, beginning in 1923 with Cutler’s successful case of a closed mitral commissurotomy with a tenotomy knife at the Peter Bent Brigham Hospital in Boston.1 The only successful heart operations done before 1953 were closed techniques for mitral stenosis,2 a few clinical experiments in 1952 with “open” heart by deep hypothermic arrest by John Lewis at the University of Minnesota,3 and the “blue-baby” operations of the 1940s and 1950s.4 It is not a fluke that John Gibbon was the first to do this procedure. He had studied and worked tirelessly on this project for 23 years before the first successful application. Dr Gibbon, who would have also celebrated his one-hundredth birthday in 2003, was a medical student at Jefferson and finished his residency in surgery at the Pennsylvania Hospital in the late 1920s. In 1930, he obtained a research fellowship with Dr Edward Churchill, the Chief of Surgery at the Massachusetts General Hospital in Boston. On …

A population-based study of appetite-suppressant drugs and the risk of cardiac-valve regurgitation.

Recent case reports suggest that a combination of the appetite suppressants fenfluramine and phentermine is associated with an increased risk of cardiac-valve regurgitation. There are also reports of valvular disorders in persons taking fenfluramine or dexfenfluramine alone, particularly for more than three months. We conducted a population-based follow-up study and a nested case-control analysis of 6532 subjects who received dexfenfluramine, 2371 who received fenfluramine, and 862 who received phentermine to assess the risk of a subsequent clinical diagnosis of a valvular disorder of uncertain origin. For comparison, we identified a group of 9281 obese subjects who had not taken appetite suppressants who were matched to the treated subjects for age, sex, and weight. All subjects were free of diagnosed cardiovascular disease at the start of follow-up. The average duration of follow-up for all subjects was about four years. There were 11 cases of newly diagnosed idiopathic valvular disorders, 5 after the use of dexfenfluramine and 6 after the use of fenfluramine. There were six cases of aortic regurgitation, two cases of mitral regurgitation, and three cases of combined aortic and mitral regurgitation. There were no cases of idiopathic cardiac-valve abnormalities among the subjects who had not taken appetite suppressants or among those who took only phentermine. The five-year cumulative incidence of idiopathic cardiac-valve disorders was 0 per 10,000 subjects among those who had not taken appetite suppressants (95 percent confidence interval, 0 to 15.4) and among those who took phentermine alone (95 percent confidence interval, 0 to 76.6), 7.1 per 10,000 subjects among those who took either fenfluramine or dexfenfluramine for less than four months (95 percent confidence interval, 3.6 to 17.8; P=0.02 for the comparison with subjects who had not taken appetite suppressants), and 35.0 per 10,000 subjects among those who received either of these medications for four or more months (95 percent confidence interval, 16.4 to 76.2; P<0.001). The use of fenfluramine or dexfenfluramine, particularly for four months or longer, is associated with an increased risk of newly diagnosed cardiac-valve disorders, particularly aortic regurgitation.