Each Congenital Heart Defect Has a Distinctive Murmur Pattern. Here Is When to Refer to Pediatric Cardiology.

What It Is

Why the Differential Changes Across the Lifespan

The murmurs heard at different ages reflect the age-specific prevalence of underlying conditions:

Newborn period (0 to 3 months): Murmurs are common in newborns because of the normal transition from fetal to postnatal circulation. The foramen ovale closes in the first hours to days; the ductus arteriosus normally closes by 24 to 48 hours. Murmurs in this period may be transitional (and benign) or may represent significant congenital heart disease that requires intervention within days.

Infancy and early childhood (3 months to 5 years): Congenital defects are the dominant murmur source. Ventricular septal defects, atrial septal defects, patent ductus arteriosus, and pulmonic stenosis are the most common pathological murmurs. Innocent murmurs (Still’s murmur, pulmonary flow murmur) emerge in this period as well.

School age and adolescence (5 to 18 years): Innocent murmurs peak and then decline. Previously undetected congenital defects (particularly ASDs and small VSDs) may be first identified. Acquired rheumatic disease, now rare in the US but common globally, may appear. HCM may present with its exertional murmur.

Young adulthood and beyond: Congenital murmurs that were never repaired or that have residual hemodynamic consequences after repair. Acquired valvular disease (degenerative AS, MR, AR) begins to emerge. Murmur diagnosis shifts from congenital to acquired pathology.

The Mechanism

Ventricular Septal Defect (VSD)

VSD is the most common congenital heart defect, occurring in 3 to 4 per 1,000 live births 5 / Solid 01886-7). An opening in the interventricular septum allows blood to shunt from the high-pressure left ventricle to the lower-pressure right ventricle (left-to-right shunt).

The murmur of VSD is holosystolic, harsh, grade 3 to 5/6, loudest at the left lower sternal border, often with a palpable thrill. In small (“restrictive”) VSDs, the high pressure gradient across the small defect produces a loud murmur (the maladie de Roger). Paradoxically, very large VSDs may produce softer murmurs because the LV-RV pressure difference is small.

Natural history: approximately 30 to 40 percent of small muscular VSDs close spontaneously in the first two years of life 5 / Solid . Perimembranous VSDs have a lower spontaneous closure rate. Large unrepaired VSDs lead to pulmonary overcirculation, pulmonary hypertension, and eventually Eisenmenger syndrome.

Atrial Septal Defect (ASD)

ASD occurs in 1 to 2 per 1,000 live births. The three anatomical types are:

• Secundum ASD (70 to 75%): In the fossa ovalis, the midportion of the atrial septum.
• Primum ASD (15 to 20%): Adjacent to the AV valves; associated with partial atrioventricular canal defects and mitral cleft.
• Sinus venosus ASD (5 to 10%): Near the SVC-RA junction, associated with anomalous pulmonary venous drainage.

The ASD murmur is not produced by the defect itself. The defect causes a left-to-right atrial shunt, increasing right heart volume, which produces increased flow across the pulmonic valve. The murmur is a soft systolic ejection murmur at the left upper sternal border (pulmonic area), accompanied by fixed splitting of S2 (the pulmonic component of S2 is delayed by increased RV stroke volume and does not vary with respiration, unlike normal splitting). Fixed S2 splitting is the clinical hallmark of ASD 5 / Solid .

ASD is the classic “late presentation” congenital defect: many are not detected in childhood, may produce minimal symptoms for decades, and present in the third to fifth decade with exertional dyspnea, palpitations from atrial arrhythmias (including AF from atrial enlargement), or RV dilation on routine echo. The woman in the opening scene is a prototypical example.

ASD closure (via transcatheter Amplatzer or Gore Cardioform device for secundum defects; surgical for primum or sinus venosus defects) reduces RV volume overload, prevents pulmonary hypertension progression, and reduces AF risk 5 / Solid .

Patent Ductus Arteriosus (PDA)

The ductus arteriosus connects the pulmonary artery to the descending aorta in fetal circulation, diverting blood away from the non-functional fetal lungs. It normally closes at 24 to 48 hours of life. A PDA that remains open produces a continuous (“machinery”) murmur at the left infraclavicular area: the murmur persists through both systole and diastole because the aortic pressure exceeds pulmonary artery pressure throughout the cardiac cycle.

Premature infants are at highest risk for PDA. In term infants, spontaneous closure within the first year is common for small PDAs. Large PDAs require intervention (catheter-based occlusion with Amplatzer duct occluder, or surgical ligation in premature infants for whom catheter intervention is less feasible) 5 / Solid .

Pulmonic Stenosis

Pulmonic stenosis (PS) produces a harsh systolic ejection murmur at the left upper sternal border with a systolic ejection click (a brief high-pitched sound just after S1 caused by the doming stenotic valve). The ejection click of PS is the only right-sided click that decreases with inspiration. The murmur radiates to the left clavicle and back.

PS is usually isolated and valvular in etiology (domed pulmonic valve, distinct from the subvalvular infundibular stenosis seen in tetralogy of Fallot). Mild PS (peak gradient < 30 mmHg) is well-tolerated indefinitely. Moderate-to-severe PS (peak gradient > 40 mmHg) benefits from balloon pulmonic valvotomy 5 / Solid .

The Congenital Defects Associated with Down Syndrome

Down syndrome (trisomy 21) is associated with congenital heart disease in approximately 40 to 50 percent of affected individuals 5 / Solid . The most common lesion is atrioventricular septal defect (AVSD, also called complete AV canal): a primum ASD with a VSD and cleft mitral and tricuspid valve leaflets. The murmur reflects both the AV valve regurgitation (holosystolic) and the increased pulmonic flow (ejection murmur). AVSD requires surgical repair in infancy to prevent irreversible pulmonary hypertension.

The Murmur of Tetralogy of Fallot

Tetralogy of Fallot (TOF) is the most common cyanotic congenital heart defect, accounting for approximately 10 percent of all congenital heart disease. Its four components are: RV outflow tract obstruction, large VSD, overriding aorta, and right ventricular hypertrophy.

The murmur of TOF is a systolic ejection murmur from the RV outflow obstruction, louder than the VSD component (because the RVOTO creates the primary turbulence). Unlike unrepaired simple VSD, TOF murmur does not have a prominent holosystolic quality because the VSD pressure gradient is reduced by the equal (or suprasystemic) RV pressure from the outflow obstruction. Cyanosis, not just murmur, defines the clinical presentation.

How We Diagnose / How It Is Used

Neonatal Echocardiographic Screening

In the United States, pulse oximetry screening for critical congenital heart disease (CCHD) has been universally recommended for all newborns since 2011 5 / Solid . Pre- and post-ductal SpO2 measurement at 24 hours detects the majority of CCHD lesions dependent on ductal patency, though it misses some aortic valve and arch lesions and atrial level defects.

Echocardiographic screening of all newborns is not currently standard in the US (unlike some European countries). Screening is performed on infants with abnormal pulse oximetry, detected murmurs, or clinical features suggesting cardiac disease.

Physical Examination Across the Lifespan

In the newborn: The cardiac examination includes heart rate, respiratory rate, liver edge position (hepatomegaly from right heart failure), femoral pulses (absent or weak in coarctation of the aorta), oxygen saturation differential (pre-ductal vs post-ductal).

In the child: The examination should include measurement of supine blood pressure in both arms (coarctation of the aorta produces a blood pressure gradient between the arms and legs), careful auscultation in multiple positions, and documentation of the S2 splitting (fixed splitting for ASD).

In the adolescent and young adult: Dynamic auscultation for HCM (standing increases murmur), auscultation for the late systolic click of MVP (most common cardiac abnormality in young women), and screening for features of Marfan syndrome (tall stature, arm span > height, pectus deformity, arachnodactyly, high-arched palate) for which aortic root dilation is a primary cardiac concern.

The ACHD Clinic: Who Should Be There

The American College of Cardiology/American Heart Association 2018 ACHD Guidelines 5 / Solid categorize ACHD patients by complexity:

Simple ACHD (managed by general cardiologist): Small VSD (no hemodynamic significance), small ASD (closed transcutaneously), isolated mild pulmonic stenosis, mild bicuspid aortic valve (no dilation).

Moderate ACHD (periodic ACHD specialist evaluation): Significant VSDs, ASDs (unrepaired or repaired with residual), coarctation of the aorta (repaired), Ebstein anomaly (mild/moderate), single uncomplicated pulmonic valve disease.

Complex ACHD (all care at ACHD center): TOF (repaired or unrepaired), Eisenmenger syndrome, Fontan circulation, congenitally corrected transposition, pulmonary arterial hypertension from Eisenmenger.

Adults with moderate or complex ACHD should be followed at an ACHD center with a dedicated adult congenital cardiologist, not a general cardiology practice. The physiological complexity of these patients requires expertise that most general cardiologists do not maintain.

Pregnancy and ACHD: The Specific Risk Calculation

Pregnancy in women with ACHD requires specialized management. The CARPREG II risk score (Silversides et al., JACC 2018) provides a validated risk stratification tool for cardiac complications during pregnancy. Women with moderate-to-severe pulmonary stenosis, systemic right ventricle, Fontan circulation, or pulmonary arterial hypertension face the highest risks (maternal mortality rates of 25 to 50 percent with Eisenmenger syndrome).

The woman in the opening scene, with a large ASD and raised pulmonary pressures at 34 weeks, needed immediate cardio-obstetrics coordination, a plan for delivery, and post-delivery ASD closure before another pregnancy.

The Evidence

Prevalence and Outcomes

Adult Congenital Heart Disease Epidemiology

The number of adults with congenital heart disease in the US now exceeds the number of children with CHD, an inversion that occurred in the late 1980s as surgical outcomes improved 5 / Solid . This population faces a set of late complications that were not anticipated when the original surgical repairs were designed:

• Repaired TOF: RV dilation from pulmonary regurgitation after transannular patch repair; pulmonary valve replacement required when RV end-diastolic volume index > 160 mL/m2
• Repaired coarctation of the aorta: Residual hypertension, late aortic aneurysm at repair site
• Fontan circulation: Progressive Fontan failure, protein-losing enteropathy, plastic bronchitis, hepatic fibrosis
• Repaired TGA: Late RV failure (systemic right ventricle), complete heart block

Eisenmenger Syndrome: The Natural History of Uncorrected Large Left-to-Right Shunts

Eisenmenger syndrome describes the reversal of a left-to-right shunt to right-to-left due to pulmonary arterial hypertension, producing cyanosis. It develops in approximately 10 percent of large unrepaired VSDs and PDAs and a smaller percentage of ASDs 5 / Solid . Once established, Eisenmenger syndrome is not reversible by shunt closure; closure would remove the RV’s only pressure outlet. Management is with pulmonary arterial hypertension-targeted therapy (bosentan, macitentan, sildenafil, tadalafil). Median survival to age 50 to 60 in contemporary ACHD centers 4 / Promising .

The Patient Experience

The “Watched” Childhood Murmur in the Adult Office

When an adult patient mentions that they “had a murmur as a child that was watched,” the cardiologist must determine: what was being watched, what was found, and what happened subsequently. The possibilities range from an innocent murmur that resolved (no action needed) to a small VSD that closed (no action needed) to a moderate ASD that was never repaired (potentially significant now) to a bicuspid aortic valve that has been enlarging its associated aortic root for thirty years without anyone noticing.

The clinical approach: obtain prior records if possible. Perform careful auscultation and echocardiography if the history is uncertain. Do not assume that because no one seemed alarmed in childhood, nothing is wrong.

The Conversation That Did Not Happen at Age Eighteen

The transition from pediatric cardiology to adult cardiology is one of the highest-risk periods for ACHD patients. Patients who have been followed in pediatric programs until age 18 to 21 often disengage from care in young adulthood: they feel well, they are busy, the pediatric program no longer follows them, and no one explicitly hands them to an ACHD center. The data show that 30 to 50 percent of ACHD patients have gaps in care of more than three years at some point 5 / Solid .

During those gaps, subclinical deterioration occurs: arrhythmias develop, valves deteriorate, RV function declines. When these patients re-enter care in their thirties or forties (often triggered by pregnancy, palpitations, or incidental echo), they are often at a later stage of their disease than the pediatric cardiologist would have allowed.

The ACHD transition program, which includes explicit planning for the transfer of care to an adult ACHD specialist, is the structural solution. Many pediatric programs now include this in their care pathway, but implementation is imperfect.

Decisions and Trade-Offs

When to Close an ASD in an Adult

The threshold for ASD closure in adults is hemodynamic significance: Qp:Qs above 1.5 (more than 50 percent extra pulmonary flow compared to systemic), RV volume overload on echocardiography, or pulmonary arterial pressure below 2/3 systemic (if pulmonary pressures are too high, closure carries risk) 5 / Solid .

Transcatheter closure with the Amplatzer Septal Occluder (Abbott, FDA-cleared PMA device) is preferred for secundum ASDs with adequate rims. Success rates above 97 percent for complete closure, complication rate approximately 1 percent for major events. Surgical closure is required for primum and sinus venosus defects.

Pulmonary Valve Replacement in Repaired TOF

The timing of pulmonary valve replacement (PVR) in adults with repaired TOF and chronic pulmonary regurgitation is one of the most debated topics in ACHD management. The current Class I indication: PVR when RVESVI > 80 mL/m2 or RVEDVI > 160 mL/m2, declining RV function, severe PR with symptoms, or sustained ventricular arrhythmia 5 / Solid .

The transcatheter pulmonic valve replacement (TPVR, Melody valve or Sapien-XT pulmonic, both FDA-cleared) is now available for patients with adequate conduit anatomy, avoiding repeat open surgery. For patients with native RVOT anatomy from prior transannular patch repair, surgical PVR with a tissue valve or homograft remains standard.

The Genetics of Congenital Heart Disease

Approximately 20 to 30 percent of congenital heart disease has an identifiable genetic cause: chromosomal (Down syndrome, 22q11 deletion for conotruncal defects), single-gene mutations (NOTCH1 for bicuspid aortic valve families, MYH7, MYBPC3 for HCM), or copy number variants 5 / Solid .

First-degree relatives of individuals with CHD have a 2 to 10 percent risk of a cardiac defect, depending on the specific lesion. Genetic counseling and cardiac screening of first-degree relatives is appropriate for many CHD diagnoses, particularly for conditions with known genetic architecture (bicuspid aortic valve, HCM, AVSD in Down syndrome families, conotruncal defects from 22q11).

Clinical Synthesis

Pediatric and adult congenital heart disease murmurs span the widest range of clinical significance in cardiology: from the innocent murmur that resolves before kindergarten to the Eisenmenger syndrome requiring a multidisciplinary evaluation at an ACHD center. The common thread is that every murmur discovered in a child, and every “watched” or “corrected” cardiac lesion from childhood, deserves a current clinical assessment at some point in adulthood.

The program addresses the ACHD transition gap directly:

In the Chicago metropolitan area, Northwestern Memorial Hospital and the University of Chicago Medicine have dedicated ACHD programs. Lurie Children’s Hospital provides transition planning and adult referral. In Champaign-Urbana, Carle Foundation Hospital provides initial ACHD evaluation with referral to Chicago-based ACHD centers for complex cases. In rural central Illinois, patients with ACHD identified or suspected at regional hospitals should be referred to Peoria’s Children’s Hospital of Illinois or Chicago ACHD centers.

The woman who arrived at the Chicago cardio-obstetrics clinic at 34 weeks with an unrepaired, hemodynamically significant ASD she did not know about should not have been in that situation. A structured cardiovascular assessment would have flagged her history two or three pregnancies earlier. She would have had her echocardiogram in her late twenties, her ASD closed before any pregnancy, and she would have walked into this pregnancy with a structurally repaired heart.

That is the preventive architecture this program is built around.

Tetralogy of Fallot and Complex Congenital Heart Disease: What Adults Need to Know

Tetralogy of Fallot is the most common cyanotic congenital heart disease, accounting for approximately 10 percent of all CHD 5 / Solid . The four components ( ventricular septal defect, overriding aorta, right ventricular outflow tract obstruction (RVOTO), and right ventricular hypertrophy ) together produce a clinical picture that, without intervention, leads to progressive cyanosis, clubbing, polycythemia, and death in childhood in most cases.

Surgical repair of TOF has been performed since the 1950s, with the Blalock-Taussig-Thomas shunt providing the first palliative option (1944) and complete intracardiac repair established by the 1960s. Today, complete repair is performed in infancy, typically between 3 and 6 months of age, with hospital mortality below 1 percent at high-volume centers 5 / Solid . The cohort of adults alive today with repaired TOF numbers in the hundreds of thousands in the United States alone.

The murmur in unrepaired TOF is a harsh systolic ejection murmur at the LUSB, produced by flow across the stenotic RVOT. After complete repair, the murmur pattern changes: a residual pulmonary regurgitation murmur (soft early diastolic, LUSB) is common, along with residual RVOTO murmur in some patients. Pulmonary regurgitation after TOF repair is the central long-term management problem: chronic PR causes RV dilation, RV dysfunction, arrhythmias, and ultimately right heart failure.

The ACHD Surveillance Imperative

Adults with repaired CHD represent the fastest-growing segment of the ACHD population. There are now more adults with CHD in the United States than children with CHD, approximately 1.4 million adults versus 1 million children 5 / Solid . This shift occurred because surgical and medical advances converted previously fatal conditions into manageable chronic diseases. It created a population that requires lifelong subspecialty surveillance but was not uniformly transitioned from pediatric cardiology care into adult ACHD programs.

The transition failure is well-documented. Studies of ACHD populations in multiple countries find that a substantial minority ( estimates range from 30 to 60 percent ) experience gaps in care during the transition from pediatric to adult cardiology, sometimes lasting years 5 / Solid . During these gaps, patients develop complications including LV dysfunction, arrhythmias, infective endocarditis, and hemodynamic deterioration that would have been detected and managed under continuous surveillance.

The ACHD clinic at Northwestern Medicine in Chicago and the University of Chicago Medicine provide dedicated transition programs with structured handoff protocols. Lurie Children’s Hospital maintains a formal transition program with defined age-based milestones and written transition readiness assessments. In Champaign-Urbana, Carle Foundation Hospital provides initial ACHD evaluation with echocardiography and cardiac MRI capability, with complex cases referred to Chicago-based ACHD programs for surgical or catheter-based intervention.

The murmur heard in the adult ACHD patient in a general cardiology or primary care clinic is often the first clinical signal prompting evaluation of a gap in ACHD follow-up. The 38-year-old with a childhood history of “heart surgery” who presents to a Champaign primary care practice with a new murmur and no cardiologist in over 10 years represents a patient who has lived through the transition gap and has, until that murmur, not been detected. That conversation, and the clinical pathway that follows it, defines whether the next decade of that patient’s life is spent with managed or unmanaged complex CHD.

Infective Endocarditis Risk in Congenital Heart Disease

Patients with unrepaired or residual CHD are among the highest-risk populations for infective endocarditis. The endothelial disruption created by abnormal intracardiac flow, the presence of turbulent jets, and the foreign material from prosthetic valves or closure devices all create surfaces susceptible to bacterial seeding.

The 2007 AHA revision of endocarditis prophylaxis guidelines substantially narrowed the indications for antibiotic prophylaxis before dental procedures. Current Class I indications include:

1. Prosthetic cardiac valves (mechanical or bioprosthetic)
2. Prior IE
3. Unrepaired cyanotic CHD, including palliative shunts and conduits
4. Repaired CHD with residual defects adjacent to prosthetic material
5. Cardiac transplant recipients with structural valve abnormalities 5 / Solid

Patients with simple, successfully repaired defects (e.g., ASD or VSD closed with no residual defect, confirmed 6 months after closure) do not require endocarditis prophylaxis. This is frequently misunderstood: the patient who received a ventricular septal defect closure device at age 3, had a normal echocardiogram at the 6-month follow-up, and is now 25 years old does not need amoxicillin before dental cleanings. The patient with a residual small VSD adjacent to the closure device does.

The cardiologist’s role is to communicate the endocarditis prophylaxis status clearly to the patient’s dentist, oral surgeon, and primary care team, and to update that status when it changes. An the patient with CHD has their prophylaxis status documented in plain English in their care summary, not buried in an echocardiogram report.

Ventricular Septal Defect: Spectrum and Natural History

The ventricular septal defect is the most common congenital heart defect at birth, present in approximately 1 in 250 live births 5 / Solid . The clinical spectrum is enormous: small, restrictive VSDs produce a loud, high-pitched pansystolic murmur at the lower left sternal border but cause minimal hemodynamic consequence and close spontaneously in the majority of cases. Large, non-restrictive VSDs produce left-to-right shunting with volume overload of the LV and pulmonary vasculature, and require surgical or catheter-based closure.

The natural history of the small VSD is generally favorable. In infants with small muscular VSDs (the most common type), spontaneous closure rates by age 5 exceed 80 percent 5 / Solid . Perimembranous VSDs close spontaneously in approximately 35 to 40 percent of cases. Outlet (supracristal) VSDs rarely close spontaneously and are associated with aortic valve prolapse, which increases over time.

The patient referred for evaluation of a pansystolic murmur at the LLSB at age 6 months, confirmed as a small restrictive VSD by echocardiography, can be followed clinically with annual echocardiograms until the VSD closes. If it remains patent at age 3 to 5 without evidence of LV dilation, raised pulmonary pressures, or aortic valve prolapse, observation continues. The child with a large VSD manifesting with failure to thrive, recurrent respiratory infections, tachycardia, and raised Qp/Qs by echo is referred for closure without waiting for natural history.

The irreversible complication of an uncorrected large left-to-right shunt is Eisenmenger syndrome: the chronically raised pulmonary blood flow causes progressive pulmonary vascular disease, rising pulmonary vascular resistance, and ultimately reversal of the shunt direction from left-to-right to right-to-left. Once Eisenmenger physiology is established, closure of the VSD is contraindicated because it removes the only remaining pressure relief for the RV. The pulmonary hypertension is managed medically with pulmonary vasodilators (sildenafil, bosentan, macitentan), but the prognosis is poor with median survival from symptom onset measured in years 5 / Solid .

Eisenmenger syndrome is a preventable complication. The window for closure is childhood, not adulthood. The pathway to this complication runs through missed echocardiograms, delayed referrals, and lost follow-up in the transition years. A structured cardiovascular assessment framework identifies patients with known or suspected CHD who are outside the appropriate surveillance window and initiates re-engagement before irreversible physiology develops.

Genetic Syndromes and Cardiac Murmurs: The Family History as a Diagnostic Tool

Several genetic syndromes associate predictably with specific congenital heart defects and produce recognizable murmur patterns. Identifying the syndrome diagnoses not just the cardiac lesion but the broader clinical framework for the patient and their family.

Down Syndrome (Trisomy 21)

Approximately 40 to 50 percent of children with Down syndrome have congenital heart disease 5 / Solid . The most common lesion is the atrioventricular septal defect (AVSD, also called atrioventricular canal defect), present in approximately 40 to 45 percent of CHD in Down syndrome patients. The complete AVSD produces a large central cardiac defect combining an ostium primum ASD with an inlet VSD and a common atrioventricular valve.

The murmur in complete AVSD is complex: a pansystolic murmur from the VSD component and AV valve regurgitation, with potential mid-diastolic flow rumble from the common AV valve. The hemodynamic burden of unrestricted left-to-right shunting requires surgical repair, typically at 3 to 6 months of age before Eisenmenger physiology develops. Children with Down syndrome have a susceptibility to early and accelerated pulmonary vascular disease, potentially from abnormal pulmonary vascular development, making early repair even more pressing 4 / Promising .

Routine echocardiography is recommended for all newborns with Down syndrome, regardless of the presence or absence of an audible murmur, because the physical examination is unreliable in this setting: some significant CHD in trisomy 21 is clinically silent in the neonatal period.

Turner Syndrome (45,X)

Turner syndrome affects approximately 1 in 2,500 live female births and is associated with a 25 to 35 percent rate of cardiovascular malformations 5 / Solid . The most common cardiac lesion is bicuspid aortic valve, present in approximately 30 percent. Coarctation of the aorta is present in approximately 12 percent. Aortic dilation and the risk of aortic dissection are the most serious cardiovascular complications, occurring at higher rates and younger ages than in the general population.

The bicuspid aortic valve in Turner syndrome produces the same systolic ejection murmur as other bicuspid aortic valves. The critical addition is the aortic dimension surveillance: women with Turner syndrome require periodic MRI or CT of the entire aorta, not just echocardiography of the valve, because dissection risk correlates with aortic size index (ASI = aortic root diameter/BSA) and the risk is raised even at dimensions that would not trigger intervention in non-Turner patients. An ASI above 2.5 cm/m² carries raised dissection risk in Turner syndrome 5 / Solid .

The woman with Turner syndrome and a known bicuspid aortic valve who presents to a general cardiology practice needs more than a valve evaluation. She needs an aortic imaging protocol, a blood pressure evaluation (hypertension is common in Turner syndrome and directly amplifies aortic dissection risk), an assessment of estrogen status (premature ovarian failure increases cardiovascular risk), and a discussion about pregnancy risk if she is considering conception.

Noonan Syndrome

Noonan syndrome, caused by gain-of-function mutations in RAS/MAPK pathway genes (PTPN11 in approximately 50 percent of cases), presents with a recognizable facial phenotype, short stature, pectus deformity, and CHD in 50 to 80 percent of cases 5 / Solid . The most common cardiac defect is pulmonary valve stenosis (in approximately 50 to 60 percent of CHD-affected individuals), followed by hypertrophic cardiomyopathy (in approximately 20 percent) and ASD.

The pulmonic stenosis murmur in Noonan syndrome may be atypical: the Noonan PS often involves valve dysplasia (thickened, dysplastic leaflets) rather than simple commissural fusion, which makes the murmur softer and shorter than typical PS, and makes balloon pulmonary valvuloplasty less effective as a treatment (dysplastic valves do not fracture cleanly with balloon dilation; surgical relief is often needed) 4 / Promising .

The HCM in Noonan syndrome deserves separate attention. RAS/MAPK-pathway HCM may respond differently to RAAS inhibition than sarcomere-mutation HCM, and the MEK inhibitor trametinib has shown early evidence of LV hypertrophy regression in Noonan HCM in case series 3 / Early . This represents an emerging pharmacological approach to a genetic cardiomyopathy that has historically been managed only with beta-blockade and device therapy.

The genetic syndrome patient presenting with a murmur in an adult general cardiology practice is often accompanied by a childhood history of cardiac procedures, a complex medical record spanning pediatric cardiology programs, a gap in subspecialty follow-up during the transition years, and incomplete communication between subspecialty and primary care. A structured cardiovascular assessment framework is designed to identify and close this gap: bringing the adult with genetic syndrome CHD into a coordinated care model that addresses the cardiac, metabolic, and systemic aspects of the syndrome rather than treating the murmur in isolation.

Patent Ductus Arteriosus, Coarctation, and the Left-Sided Murmurs of Obstructive Disease

The left-sided obstructive lesions produce characteristic murmur patterns that, when recognized, lead directly to specific diagnostic and management pathways. Understanding these patterns ( their location, timing, and associated physical findings ) is the clinical skill that drives early identification.

Patent Ductus Arteriosus

The ductus arteriosus is a fetal vascular structure connecting the main pulmonary artery to the descending aorta, designed to shunt blood away from the high-resistance fetal pulmonary circulation. It normally closes within 24 to 72 hours of birth in response to increased oxygen tension and declining prostaglandin levels. A patent ductus arteriosus (PDA) represents failure of this closure.

In term infants, PDA occurs in approximately 1 in 2,000 live births 5 / Solid . In premature infants, the rate is far higher: approximately 70 percent of infants born before 28 weeks gestation have a PDA that requires management.

The clinical murmur of a hemodynamically significant PDA is the classic “machinery” or continuous murmur: it begins in systole, peaks at S2, and continues into diastole, heard best at the left infraclavicular region or LUSB. A large PDA produces wide pulse pressure, bounding peripheral pulses, and a hyperdynamic precordium. In premature infants, these clinical signs are often subtle, and the PDA is identified by echocardiography rather than auscultation.

Small PDAs in term infants, if not causing hemodynamic compromise, may be observed for spontaneous closure. Moderate-to-large PDAs require closure. Options include pharmacological closure with indomethacin or ibuprofen (in premature infants, inhibiting prostaglandin synthesis to promote ductal closure), transcatheter device closure using Amplatzer Duct Occluder or coils (now the standard approach for most PDAs in children and adults), or surgical ligation 5 / Solid .

The incidental finding of a small “silent” PDA in an adult (PDA detected only by echocardiography or Doppler, with no audible murmur) is increasingly common as echocardiography is performed more liberally. Whether to close an asymptomatic silent adult PDA remains debated, with current guidelines suggesting closure is reasonable to prevent IE risk (Class IIa; 10.1161/CIR.0000000000001001), though the absolute IE risk from a small silent PDA is low.

Coarctation of the Aorta

Coarctation of the aorta is a narrowing of the aortic lumen, typically at or near the level of the ductus arteriosus insertion (juxtaductal location). Its prevalence is approximately 4 per 10,000 live births, and it represents approximately 6 to 8 percent of CHD 5 / Solid . It is associated with bicuspid aortic valve in approximately 50 to 85 percent of cases.

The classic murmur of coarctation is a systolic ejection murmur heard best at the left infraclavicular region and interscapular area (back). The critical physical examination finding is not the murmur alone but the blood pressure differential: hypertension in the upper extremities with lower or absent pulses in the lower extremities. A right-arm-to-right-leg blood pressure differential exceeding 20 mmHg strongly suggests coarctation 5 / Solid .

Coarctation is one of the most commonly missed congenital diagnoses in adolescence. A teenager who has had blood pressure measured only in the arm, who has mild exertional headaches or leg fatigue attributed to deconditioning, and who has not had a careful examination of femoral pulse quality may carry undiagnosed coarctation for years. A simple four-extremity blood pressure measurement ( right arm, left arm, and both legs ) takes 3 minutes and identifies the coarctation pattern when present.

In the newborn period, severe coarctation presents as ductal-dependent systemic circulation: when the PDA closes, the obstruction becomes critical, and the infant develops shock, acidosis, and circulatory collapse. This is the scenario the pediatric cardiologist fears at every neonatal echocardiography consult: the infant who looks well in the nursery with the PDA open and crashes at home on day 3.

Intervention options for coarctation include surgical resection with end-to-end anastomosis or patch repair (preferred in neonates and young infants) and catheter-based balloon dilation with or without stenting (preferred in older children and adults). Recurrence (re-coarctation) after any intervention requires surveillance, and hypertension often persists even after successful repair due to aortic wall remodeling and neurohormonal changes, a fact that is frequently not communicated to patients after pediatric repair 5 / Solid .

The adult who presents to a general internist at age 35 with resistant hypertension, whose childhood history reveals a heart procedure at age 2, who has a systolic murmur at the interscapular area of the back, and whose right-arm blood pressure is 165/95 while femoral pulses are diminished, has a re-coarctation or residual gradient that has been driving uncontrolled hypertension for potentially a decade. An MRI aorta confirms the anatomy; intervention (repeat stenting or surgical repair) is planned. Without the blood pressure differential and the back murmur, this patient continues to receive antihypertensive titration without addressing the structural cause.

Pulmonary Valve Stenosis: Spectrum and Management

Pulmonary valve stenosis accounts for 7 to 10 percent of all CHD 5 / Solid . The classic murmur is a crescendo-decrescendo systolic ejection murmur at the LUSB, typically Grade 2-4/6, with radiation to the lung fields. A pulmonary ejection click precedes the murmur and distinguishes it from the innocent pulmonary flow murmur of childhood (which lacks the click). In more severe PS, the click fuses with S1 as valve opening is delayed; in very severe PS, the click may disappear entirely.

Mild PS (peak gradient below 25 mmHg) requires no intervention in the absence of symptoms and can be followed with echocardiography every 5 years. Moderate PS (peak gradient 25 to 50 mmHg) requires serial surveillance and intervention if progressive. Severe PS (peak gradient above 50 mmHg) is an indication for intervention regardless of symptoms.

Balloon pulmonary valvuloplasty is the intervention of choice for most morphologically suitable PS (non-dysplastic valve). Success rates in typical PS exceed 90 percent, with gradient reduction from above 50 mmHg to below 25 mmHg in the majority of patients 5 / Solid . Residual pulmonary regurgitation after valvuloplasty is common but usually well-tolerated for years. In dysplastic PS (as in Noonan syndrome), surgical valvotomy or replacement may be necessary.

The ACHD patient with a history of childhood balloon valvuloplasty for PS who presents to a primary care practice decades later may have a residual soft diastolic murmur from chronic pulmonary regurgitation, RV dilation, and reduced exercise tolerance that has been attributed to deconditioning. A structured ACHD evaluation with echocardiography and cardiac MRI (which provides the most accurate RV volume and function assessment) defines whether the PR is hemodynamically significant and whether pulmonary valve replacement is approaching indication.

The conversation about late pulmonary valve replacement in adults with repaired TOF or PS is one of the more complex patient education tasks in ACHD cardiology. The patient who underwent successful primary repair 30 years ago and has been living a normal life does not naturally conceive of themselves as needing another procedure. Explaining the concept of asymptomatic RV dysfunction, the threshold for irreversible RV remodeling beyond which replacement may not recover function, and the improved long-term outcomes of timely replacement versus waiting for symptoms requires exactly the kind of clinical communication discipline that this clinical framework is built to support.

The Signal Check is fifteen questions mapping the cardiovascular risk pattern across the physiological domains most commonly missed in standard screenings. It produces a specific starting point for your next clinical conversation.