Age gives crucial clues to the diagnosis of the disease. The pediatric age group with a palpable pulse with two strokes should indicate PDA with a left to right shunt. The younger patient usually points towards a diagnosis of hypertrophic cardiomyopathy with an obstruction or bicuspid valve disease, whereas mixed aortic valve disease is more common in the elderly population. Pulsus bisferiens can be more pronounced by the Valsalva maneuver.

History

Common clinical presentations are syncope, dyspnea, chest pain, and palpitations. Long-standing problems can remain asymptomatic and later can present with signs of acute pulmonary edema and heart failure. HOCM can present with sudden cardiac death and life-threatening arrhythmias, especially in younger athletes.[4]

Physical Examination

On palpation of a peripheral pulse (radial artery), two upstrokes distinguished by a mid-systolic gap in the systole are characteristic of pulsus bisferiens.

• Wider pulse pressure is seen in aortic regurgitation.[6]
• JVP examination may reveal classical 'a' wave in HOCM.
• The apex beat is displaced in severe aortic regurgitation, whereas; in HOCM double beats can be felt at the apex.
• Auscultation: On careful cardiac evaluation, various murmurs can be heard during auscultation. The following murmurs can be seen along with pulsus bisferiens, which may clinch the clinical diagnosis. Ejection systolic murmur in the aortic area (aortic stenosis), early diastolic murmur on the left sternum (AR), mid-diastolic or early diastolic low pitch rumble murmur at the apex (severe AR) which is also called as Austin Flint murmur, ejection systolic murmur along the left parasternal area (HOCM).[7]

Aortic regurgitation can also present with other clinical signs such as blanching and flushing of the forehead and face (Lighthouse sign), bobbing of the head synchronous with the arterial pulse (De Musset sign), repeated flushing and blanching of the capillaries in the nail beds (Quincke sign), alternating systolic miosis and diastolic mydriasis in both pupils (Landolfi sign), pulsations of the retinal arteries on the fundoscopic examination (Becker Sign), pulsations of the uvula (Muller sign), systolic pulsations of the liver (Rosenbach sign) and spleen (Gerhard sign), a pistol shot sound both during systole and during diastole on auscultation (Traube sign), diastolic-systolic murmur over the femoral arteries (Duroziez murmur).

Serum Biomarkers: High sensitivity troponin T (Tn-T) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels are elevated in bicuspid aortic valve disease.[8]

Chest X-Ray: Chest X-ray can reveal LVH, left atrial enlargement, and heart failure (pulmonary edema).

ECG: Conduction abnormalities, AF, left ventricular hypertrophy, and left atrial hypertrophy are seen in both aortic valvular disease and HOCM.

2D-Echo: Echocardiography is the main diagnostic tool for diagnosing mixed aortic valve disease and HOCM. Assessment of valve morphology, determination of the aortic regurgitation jet, aortic regurgitation quantification, measurement of the aortic root and ascending aorta can be done with 2D-echocardiography. Help in left ventricular assessment and measurement of its dimensions in valvular disease and hypertrophic cardiomyopathy. It also can be used to assess the morphology of the aorta and determine the feasibility of aortic surgery or valve repair.[7]

MRI: Cardiac magnetic resonance imaging is increasingly used to assess regurgitant lesion severity and ventricular function. Advances in noninvasive imaging help in objective measurements of valve disease severity, hemodynamic fluctuation, and structural complications. MRI is also used increasingly in the quantification of LV remodeling accurately. Cardiac MRI is the gold standard test in assessing patients with HOCM.[4][9]

CT: Cardiac and vascular CT has become an indispensable tool for the appropriate planning of transcatheter interventions. Useful in acquiring intracardiac and vascular access route dimensions with accuracy.[10]

Nuclear Imaging and Fluoroscopy: The extent of local infectious, metabolic activity, the extent of calcium deposits can be evaluated with nuclear imaging and fluoroscopy.

Management of pulsus bisferiens is based on its etiology. Early diagnosis and referral to the cardiologists hold the key to success in the management, reducing mortality and morbidity. Mixed aortic valve disease and hypertrophic cardiomyopathy with obstruction are the most common causes of pulsus bisferiens.

Medical Management

• Mixed Aortic Valve Disease: Vasodilators may help symptomatic patients by reducing preload and increasing cardiac output. Rate control and BP control with ACE inhibitors and ARBs might help. Beta-blockers may be less beneficial in treating patients with aortic regurgitation.[4]
• Hypertrophic Obstructive Cardiomyopathy (HOCM):  β-blockers are the first line of medical management in HOCM. Calcium channel blockers verapamil and diltiazem are beneficial too and are used as second-line in the treatment. ACE inhibitors and ARBs, because of their vasodilating properties, are better avoided. The use of vasodilators is contraindicated.
• Patent Ductus Arteriosus (PDA): Early use of indomethacin, ibuprofen, or acetaminophen to close a PDA soon after birth prevents further complications.[11] Diuretics can be used in treating acute pulmonary edema.

Surgical Management

• Mixed Aortic Valve Disease: Advances in surgical techniques, specifically those associated with valve repair; improved operative results; and enhanced perioperative management strategies, have contributed substantially to better patient outcomes. Valve-sparing surgical repair is becoming popular as a feasible alternative to routine surgeries. Transcatheter aortic valve replacement (TAVR) has revolutionized patients' treatment with symptomatic, severe aortic stenosis (AS) and now provides the least invasive treatment option for many patients.
• Hypertrophic Obstructive Cardiomyopathy (HOCM): Dual chamber pacemaker for severe HOCM and implantable cardioverter-defibrillator insertion may be indicated in the refractory ventricular arrhythmias. The surgical treatment for HOCM is myomectomy, which improves the outcome. Septal alcohol ablation may be effective in 90% of cases in severe HOCM.[12]
• Patent Ductus Arteriosus (PDA): Surgical ligation is indicated in a neonate with significant clinical PDA, but its role is controversial.[13]

An important differential diagnosis for a bisferiens pulse is a dicrotic pulse. It is always difficult to distinguish between these two clinically. In the dicrotic pulse, two peaks are palpable; one in systole and the other in diastole. Whereas in pulsus bisferiens, both peaks are seen in systole.[14] Dicrotic pulse is seen in cardiac failure, sepsis, and occasionally seen in normal individuals after an exercise.

Mixed Aortic Valve Disease: Prognosis is generally good in patients with an isolated severe aortic regurgitation (AR) who are asymptomatic and have a preserved LV function. Patients with moderate to severe AR have a poor outcome. Surgical intervention, aortic valve replacement (AVR) can improve the survival rate in symptomatic patients with LV dysfunction.

Hypertrophic Obstructive Cardiomyopathy (HOCM): The mortality rate is very low for patients with HOCM. Generally, the long-term outcome is good. A small percentage of the population has a risk of sudden cardiac death.

Patent Ductus Arteriosus (PDA): PDA severity scores have been developed, which can be used to predict serious outcomes. Ductus closes spontaneously in most healthy newborns; only 3% of the infants weighing more than 1,000 gms may require a PDA intervention.

Complications in patients who have pulsus bisferiens include:

• Heart failure
• Stroke
• Arrhythmias
• Infective endocarditis
• Sudden cardiac death

• The number of patients with the significant severe mixed aortic disease who could benefit from appropriate intervention increases age. 
• Implementing optimal treatment strategies for patients with severe aortic disease, HOCM, or PDA will improve overall outcomes. 
• Screening echocardiogram helps in early diagnosis and assess the severity of the disease.
• Screening is recommended for all first degree relatives diagnosed with HOCM as it is an inherited disease.

• Pulsus bisferiens are indicative of severe cardiac disease and must be differentiated from a dicrotic pulse.
• It is commonly seen in mixed aortic disease and hypertrophic obstructive cardiomyopathy.
• Best felt in the peripheral arteries like radial, brachial, and femoral artery.
• Echocardiography is the first-line diagnostic modality used to assess the valve severity and its impact on the left ventricle function.
• Genetic screening would help in prevention, diagnostic, and therapeutic benefits in patients with HOCM.

With the recent advances of transcatheter technologies, valve replacement techniques, and surgical repair, the community must establish institutional-based standards to deliver high-quality cardiac care. Early diagnosis at the primary care level with the involvement With the recent advances of transcatheter technologies, valve replacement techniques, and surgical repair, the community must establish institutional-based standards to deliver high-quality cardiac care.

Early diagnosis at the primary care level with providers, cardiologists, interventional cardiologists, and surgeons with timely referral to the higher center can improve outcomes. With optimal care and follow-up, serious side effects of severe aortic valve disease and HOCM such as heart failure, bacterial endocarditis, ventricular arrhythmias that lead to increased patient morbidity and mortality can be prevented. Multidisciplinary team involvement in the assessment and management of cardiac disease will lead to better outcomes.