Top Five Overseas Cardiovascular Device Companies File for IPO: Innovations in Non-Invasive Diagnostics, Heart Failure Therapies, and Pain-Free AF Treatment

Cardiovascular disease has been defined by the World Health Organization as the leading cause of death globally. In the United States, cardiovascular disease is also the primary cause of mortality. According to a report by the American Heart Association, one in every three deaths is caused by cardiovascular disease. VCBeat has compiled a list of five medical device companies in the cardiovascular field: AUM Cardiovascular, CircuLite (acquired), Heartflow, CardioKinetix, and CardiaLen. Their respective core products include electronic stethoscopes, circulatory support pumps, non-invasive computed fractional flow reserve (FFRCT) technology, left ventricular reconstruction (Parachute), and low-energy painless implantation procedures.

AUM Cardiovascular：
In 2009, located in MinnesotaAUMThe company has been established. It has developed CADence™, a non-invasive handheld device that assesses the risk of coronary heart disease in advance, thereby reducing the probability of death caused by coronary artery disease and preventing sudden cardiac death without warning signs. In essence, it functions as an electronic stethoscope placed on the chest, allowing physicians to record the resulting sounds. The device operates on the principle that turbulent flow within the coronary arteries generates unique audio signals, which are identified by proprietary algorithms embedded in the device.



The CADence™ system is indicated for all patients presenting with chest pain, or for those with at least two risk factors for coronary artery disease (CAD), such as obesity and hypertension. It is not suitable for patients who have undergone coronary artery bypass grafting (CABG) or coronary stent implantation, nor for those in whom the algorithm may be confounded, leading to false-negative or false-positive results.

Among all cardiovascular diseases, coronary atherosclerosis is the leading cause of death. The disease is caused by the accumulation of fat that forms plaques, leading to narrowing of the coronary arteries. Statistics show that 785,000 Americans are newly diagnosed with coronary artery disease each year, and 470,000 individuals with established disease experience recurrent episodes. Additionally, sudden first-time myocardial infarctions result in as many as 195,000 deaths annually. (Data source: American Heart Association [AHA], 2012)



The CEO of CADence™ is Marie Johnson, and her original motivation for founding the company stemmed from a sudden and devastating blow she experienced in her personal life. In 2002, her 41-year-old husband, Guion, passed away unexpectedly. At that time, Johnson was collaborating with scientists at 3M as a doctoral candidate, developing a computerized stethoscope. What she never could have anticipated was that this robust man—standing 188 cm tall and weighing 180 pounds—would be struck down by heart disease, leaving her forever.

The autopsy report revealed that Guion’s two coronary arteries were severely blocked, causing the left anterior descending (LAD) artery—which supplies blood to the heart—to rupture under excessive strain. Whether by coincidence or not, Johnson had collected her husband’s cardiac data in the months leading up to his death as raw material for her doctoral dissertation. Consequently, she decided to apply the principles of frequency analysis to develop an acoustic device, creating sensor algorithms to identify characteristic signals such as heart murmurs caused by turbulent blood flow.

Johnson previously served as the Program Director for the Fellowship Program at the University of Minnesota’s Center for Medical Devices. She led the development of a stethoscope system capable of recording acoustic data from the fourth intercostal space on the left side of the patient’s chest, utilizing proprietary algorithms and software to determine whether the patient’s arteries are blocked.

The CADence™ system has received regulatory approval for entry into the European market. It will initially launch in CE-certified countries in the fourth quarter of 2015. Sales in the United States will also be approved in accordance with FDA requirements.



CADence™ Product Introduction:
This technology is used to assess the likelihood of obstructive coronary artery disease in individuals presenting with chest pain or at risk for underlying conditions, offering a novel acoustic detection method for diagnosing significant coronary stenosis. The product features low cost, ease of use, non-invasiveness, and absence of radiation, thereby minimizing monitoring-related side effects.

CADence™ Product Principle:
Under normal conditions, blood flow within vessels is laminar; however, arterial obstruction can disrupt this laminar flow, creating chaotic turbulence that generates acoustic waves. Given that coronary vessels have diameters ranging from 2.5 to 5 mm, these sounds are extremely faint compared to other physiological fluctuations in the body. CADence™ employs advanced technology to overcome these challenges and detect the presence of such acoustic signals.

Experimental Process Developed by CADence™:
Establish a clinical trial center to monitor the effects of the device on specific patients. The study will separately enroll patients with severe coronary artery disease and those without coronary artery disease, assessing their myocardial blood flow perfusion status via nuclear stress testing.

A positive nuclear stress test result requires suspected patients to undergo standard coronary angiography and fractional flow reserve assessment. If the test result is negative, patients will be advised to undergo CT angiography and receive treatment as recommended by their physician.

Device Monitoring Process:
Experimental Conditions: Licensed physician, 15 minutes, handheld CADence™ device, CADence™ user manual, quiet room, internet-connected computer.
Experimental Procedure: The device collects three sets of data, uploads them to a web-based electronic database, and performs algorithm evaluation and report generation.

Financing Status:
On July 7, 2011, secured $456,000 in debt financing;
On July 10, 2015, it secured $5 million in venture capital funding.

CircuLite：
On March 5, 2013, the German company announced that its SYNERGY circulatory support system had received Investigational Device Exemption (IDE) approval from the U.S. Food and Drug Administration (FDA). The company plans to conduct a clinical trial in the United States to evaluate whether the product can deliver transformative therapeutic effects for tens of thousands of patients with end-stage heart failure. The initiation of this trial signifies that healthcare institutions and heart failure patients now have a new technological option available.

CircuLite’s SYNERGY® Circulatory System is specifically developed for patients with heart failure. Its primary component is a miniature blood pump designed for long-term implantation; the device, which is only the size of an AA battery, is implanted via a minimally invasive procedure. It is indicated for ambulatory patients with chronic heart failure who require hospitalization but whose condition is not severe enough to necessitate dependence on intravenous inotropic agents.



CircuLite’s financing history is as follows: On April 1, 2009, it secured $11.5 million in venture capital; on January 5, 2010, it raised $32.5 million in Series C funding, led by Forbion Capital, with participation from Flare Capital, Omnes Capital, and Oxford Life Sciences Investments; on November 30, 2011, it obtained $30 million in Series D financing, led by Forbion Capital, with MacAndrews & Forbes Incorporated also participating.

On December 1, 2013, HeartWare, an industry-leading innovator and a technology company focused on minimally invasive therapies for heart failure patients, announced the acquisition of CircuLite for $350 million. While CircuLite developed implantable cardiac assist devices for patients with mild symptoms, HeartWare focused more on product development for patients with severe heart failure. The transaction included $30 million in upfront consideration ($18 million in equity and $12 million in cash) and $320 million in contingent payments.

Introduction to HeartWare Products and Services:
Developed the HVAD® system to provide treatment options for heart failure patients worldwide. The product features a simple and user-friendly implantation procedure, along with broad applicability.



It features a unique integrated inflow cannula HVAD pump, suitable for patients with small ventricles undergoing implantation, while also being applicable to those with larger ventricles or obesity. Although ventricular and bodily changes occur after device implantation, the HVAD pump ensures secure fixation of the inflow cannula within the left ventricle. Its main advantages include a small incision, elimination of the need for air venting, and an optional drive system.


Whether in terms of anatomy and physiology, since each patient’s condition is unique, physicians must evaluate and flexibly adjust the approach to ensure treatment efficacy. The novel design of the HVAD® pump allows for accommodation of the diverse clinical presentations of different patients within the pericardial space through only three simple steps.


In addition to focusing on the development of small pumps, HeartWare is also developing technologies based on transcutaneous energy transfer (TET) and fully implantable electronic systems.

HeartWare's CEO and Chairman, Doug Godshall

Heartflow:
In 2007, HeartFlow, Inc. was founded in Redwood City, California. Its core product integrates high-performance computing with non-invasive fractional flow reserve derived from CT (FFRCT) technology to assist physicians in diagnosing coronary artery disease through non-invasive means.

Unlike traditional invasive procedures guided by pressure wires, HeartFlow’s fractional flow reserve technology can measure blood pressure in coronary arteries at specific locations.

Technical Platform Overview：
Advanced analytical techniques enable the creation of patient-specific hemodynamic models to non-invasively assess coronary blood flow in patients with heart disease. By utilizing FFRCT, physicians can accurately identify specific coronary lesions that may lead to myocardial ischemia. The platform integrates anatomical and functional data into visual displays, assisting clinicians in determining which patients require further invasive testing or treatment.

Platform Workflow:
1. Standard coronary artery disease CT data can be easily uploaded by physicians to HeartFlow’s cloud platform;
2. HeartFlow analysis utilizes high-performance computing to generate color-coded 3D models that display coronary FFRCT results and anatomical findings;
3. The physician receives the analysis report.

Platform's Key Advantages:
1Non-invasive Diagnosis of Cardiovascular Diseases:
Focus on the research and development of non-invasive diagnostic technologies for coronary artery disease. Based on coronary CT scans and proprietary computational fluid dynamics algorithms, it provides patient-specific coronary blood flow analysis. This offers physicians a non-invasive test that delivers functional and anatomical data to aid in the diagnosis of coronary artery disease.

FFR-CT provides physicians with additional data to determine which coronary artery lesions may lead to myocardial ischemia. The integration of cCTA (coronary CT angiography) and FFR-CT technologies helps clinicians identify patients who may require further invasive testing.

Multiple multicenter clinical studies have demonstrated that FFRCT can accurately identify significant coronary artery lesions and coronary artery lesions that do not impede blood flow.



2Improving the Accuracy of CT Diagnosis
HeartFlow conducted a clinical study to compare the diagnostic accuracy of computed fractional flow reserve (FFRCT) technology and coronary CT angiography in identifying or ruling out significant coronary artery stenosis.
Heartflow conducted annual studies in 2011, 2012, and 2013, respectively:
A 、HeartFlow NXT Study (2013)
It was the largest-scale study, involving 254 participants from 10 clinics across Europe, Asia, and Australia. The results demonstrated that FFRCT provides more accurate diagnoses than CT alone.
B、DeFACTO Study (2012)
Covering 252 patients. The diagnostic performance remains high, with an accuracy of 73% for FFRCT testing and 64% for CT alone.
C、DISCOVER-FLOW Study (2011)
Covering 103 patients, the accuracy of FFRCT testing was 84%, compared to 59% for CT alone.



3FFR-Guided Therapy Improves Treatment Outcomes and Reduces Healthcare Costs


Funding Status:
On April 19, 2010, it secured $1.6 million in venture capital funding;
On June 14, 2010, secured $10 million in debt financing;
On February 4, 2011, secured $20.4 million in venture capital funding;
On February 27, 2014, secured $104.7 million in private equity funding from Capricorn Investment Group.

CardioKinetix：
Founded in 2003, CardioKinetix is a leading medical device company specializing in catheter-based therapies for heart failure. The company has developed the Parachute series of transcatheter implants to treat heart failure. The device is implanted between the left ventricle and the damaged myocardium, isolating non-functional muscle from functional tissue to help restore normal function to the impaired myocardial segments.

The implant material consists of a fluoropolymer (expanded polytetrafluoroethylene) membrane covering a nitinol alloy frame. The umbrella-shaped device is positioned between the apex of the left ventricle and the septum formed by partial ventricular closure induced by damaged myocardium, to treat patients with ischemic heart failure.



In addition to its umbrella-shaped device, CardioKinetix has also developed other products:


Guide Catheter：
Physicians should use the guiding catheter in conjunction with the dilator to facilitate navigation to the apex of the left ventricle. Catheters of various shapes can accommodate ventricles that have undergone morphological changes.

Delivery System：
The delivery system includes two accessories: a loading funnel and a bifurcated introducer. The delivery system features a threaded tip to facilitate attachment of the umbrella-shaped device. Initially, the umbrella is folded; once in position, the loading funnel can be connected to the introducer, which transfers the device to the guiding catheter. When the implant reaches the ventricular apex, the introducer is withdrawn, and a 20 cc balloon is subsequently inflated. After the umbrella is securely anchored to the ventricle, the aforementioned balloon is deflated. The handle of the delivery system is unlocked by pulling out the blue knob, then rotated counterclockwise for five turns to detach it from the implant.

The Parachute percutaneous left ventricular partitioning device has received approval from European regulatory authorities. In October 2014, the first-in-patient clinical studies were also initiated in China, with participating hospitals including Fuwai Hospital and Shanghai Tenth People’s Hospital.

Financing Status：
On September 21, 2011, the company secured $44 million in Series E financing, with New Leaf Venture Partners (lead investor), SV Life Sciences (lead investor), JPMorgan Partners (JPMP), and U.S. Venture Partners (USVP) as investors;
On February 28, 2013, it secured $4 million in Series E financing from Panorama Capital;
On March 1, 2013, the company secured $23 million in Series E financing, led by Handing Healthcare Investment, Handing Life Sciences Investment, New Leaf Capital, Panorama Capital, and SV Life Sciences Investment.
On September 14, 2014, the Company entered into an agreement with Edwards Lifesciences to complete a $50 million Series F financing round. Co-investors included U.S. Venture Partners, Tekla Healthcare Investors, Tekla Life Sciences Investors, SV Health Investors, Panoramic Ventures, New Leaf Venture Partners, and Lexington Partners.

CardiaLen：
CardiaLen, founded in 2008 and headquartered in St. Louis, Missouri, has developed a low-energy, painless implantable device targeted at patients with atrial fibrillation (AF) undergoing cardioversion therapy.

Why Is Painless Treatment Achievable? The Core Lies in Low-Pressure Technology. It utilizes low-energy impulses that are ten times weaker than traditional high-voltage shocks, thereby ensuring no tissue damage or scarring occurs. The approach is non-toxic and allows for repeated initiation and cessation of operation. Its flexible adaptability easily accommodates the highly variable arrhythmia profiles of individual patients.

The delivery of low-energy pulses by this small implantable device will truly revolutionize the treatment of atrial fibrillation. Lower energy levels mean fewer painful side effects, and less pain translates to greater patient well-being. CardiaLen brings hope to over 9 million patients.



Atrial fibrillation is one of the most common arrhythmic disorders, affecting a combined population of 9 million in Europe and the United States. In the United States alone, atrial fibrillation causes 80,000 deaths annually and incurs substantial healthcare costs, with direct treatment expenditures amounting to $7 billion and €16 billion.

Current treatment options have limited efficacy and are associated with various adverse effects, such as the toxicity of antiarrhythmic drugs, pain caused by high-intensity external cardioversion therapy, and irreversible scarring resulting from atrial defibrillation, cardiac ablation, and surgical procedures.

Paula Skjefte is the CEO of CardiaLen. With over 30 years of experience in the healthcare industry, she previously served as a senior executive and Vice President at Medtronic. She is also the former President and Chief Executive Officer (CEO) of Watford Consulting. Ms. Skjefte has held senior board positions at numerous U.S. and international medical companies. She is an NACD Fellow and serves on the Board of Directors of Women Corporate Directors. She frequently delivers keynote addresses on successful strategies for building high-growth enterprises within regulated healthcare markets. Ms. Skjefte holds a Master of Business Administration (MBA) from the University of Minnesota and a Bachelor of Science in Nursing from the University of Wisconsin.

First from the left: Paula Skjefte

Cardialen holds a pioneering U.S. patent. Additional patents surrounding this core technology have been filed, and new U.S. provisional patents have all been published. Furthermore, Cardialen has obtained an exclusive global license for low-energy cardiac cardioversion technology, authorized by Washington University in St. Louis and formerly by Case Western Reserve University.



Funding Status:
On August 17, 2009, it secured $337,400 in debt financing;
On December 19, 2011, secured $2.4 million in debt financing from Broadview Capital;
On September 1, 2012, the company secured $138,000 in angel financing from St. Louis Arch Angels;
On January 20, 2014, it secured $2.5 million in Series A financing;
On March 26, 2015, the company secured $1.5 million in Series B financing from investors including BELLE Capital, BioGenerator, Peiyu Capital, Hualun Angels, LAMBDA Fund Management, St. Louis Arch Angels, and Twin Cities Angels.