Arising from: Mohl et al. (2008) Is activation of coronary venous cells the key to cardiac regeneration? Nat Clin Pract Cardiovasc Med 5: 528–530 [doi:10.1038/ncpcardio1298]

Response to: Mohl et al. (2009) Coronary venous pressure elevation 'risks and benefit'. Nat Clin Pract Cardiovasc Med 6: [doi:10.1038/ncpcardio1476]

We thank Professor Mohl and colleagues for raising the concept of 'embryonic recall' as an alternative link between coronary sinus activation and cardiac regeneration.1 This well-written viewpoint shed some more light on a very simple and feasible approach to recover the jeopardized myocardium.

Mercier Fauteux (1946) reported on the first patients who underwent coronary venous ligation2 and Claude Beck operated on the first patients just 11 years later, in 1948.3

In the mid-1990s we investigated the upside-down strategy to support ischemic myocardium—decrease, instead of increase, the output coronary flow and manipulate the intact coronary veins instead of the diseased coronary arteries. Our initial studies in pig models proved that either acute permanent occlusion or constriction of the coronary sinus enriches epicardial and intramyocardial blood vessels network (i.e. neovascularization).

Keeping in mind these observations we both had the great honor to invent the first percutaneous intravenous coronary sinus reducer stent (CSRS) and give it the name “Neovasc”, later known as Neovasc Medical, Inc.

The first human study of the CSRS was started in 2004.4 In this prospective, open-label, multicenter, safety feasibility study the CSRS was percutaneously implanted in 15 patients who had refractory angina pectoris despite optimal medical treatment. Two patients had class IV Canadian Cardiovascular Society (CCS), 12 had class III CCS and one had class II CCS. Six patients underwent previous percutaneous coronary artery interventions, four patients had suffered acute myocardial infarction and three underwent a previous CABG operation. Mean follow-up was 11 ± 1.03 months.

No procedural related complications were observed. All patients were discharged from hospital 1–2 days after CSRS implantation. No major adverse cardiac events were reported during the follow-up period. Six months after CSRS implantation, most of the patients had improved their CCS scores compared to baseline (3.07 vs 1.64; P <0.0001). Improvements were also observed for stress-induced ST-segment depression and for the extent and severity of myocardial ischemia, as shown by either dobutamine echocardiography or thallium single-photon emission CT.

Mohl and colleagues speculated that prolonged and uncontrolled elevation of coronary venous pressure may cause severe adverse effects and impairment in myocardial recovery.1 Our findings contradict this speculation.4 Furthermore, Mohl et al.1 also affirm that the basis for their statement is the high mortality seen in second stage Beck II operations. Second stage Beck II operation has very little in common with permanent coronary sinus constriction procedures, such as CSRS implantation. First stage Beck II operation involves interposition of a vein graft between the aorta and the coronary sinus. Second stage is done three weeks later and involves partial ligation of the coronary sinus over a probe. Both operations are done using large thoracotomy incisions. Two large thoractomies, acute elevation of coronary sinus pressure to near systemic values and further acute elevation of coronary sinus pressure three weeks later are critical enough to be a risk factor for increased mortality. On the other hand, permanent but mild increase (just a few mmHg) in coronary sinus pressure has nothing to do with increased mortality or procedural related complications, as shown by our study.4