Patent ID: 12236581

DESCRIPTION OF EXEMPLARY EMBODIMENTS

The details of one or more embodiments of the presently-disclosed subject matter are set forth in this document. Modifications to embodiments described in this document, and other embodiments, will be evident to those of ordinary skill in the art after a study of the information provided in this document. The information provided in this document, and particularly the specific details of the described exemplary embodiments, is provided primarily for clearness of understanding and no unnecessary limitations are to be understood therefrom. In case of conflict, the specification of this document, including definitions, will control.

Embodiments of the system as disclosed herein provide for defining and classifying aortic aneurysm anatomy according to diameters at multiple points of reference.

With reference to the embodiment ofFIG.1, an aorta10of a patient, in which an aneurysm30has formed, includes a proximal treatment segment defined by the diameters at four points of reference (D1-D4) and their relative position (L1-L4) to characterize the interaction between a device, such as the endograft50illustrated inFIG.1, and the proximal seal zone of the aorta10. As used herein, the diameters are taken to be the outer diameter of the blood vessel. However, inner diameter measurements can also be utilized without departing from the spirit and scope of the present invention.

A first diameter, D1, indicates the Start of Devices. In the embodiment illustrated inFIG.1, the Start of Devices is defined as the most proximal end52of the fabric covered portion of the main aortic endograft50that is at least partially apposed to the wall of the aorta10. However, generally speaking, D1indicates the most proximal extent of any therapies used in the treatment of an aneurysm.

A second diameter, D2, indicates a Lowest Preserved Branch Vessel (LPBV) of the aorta. The Lowest Preserved Branch Vessel refers to the pertinent branch vessels of the proximal sealing segment and is defined as the aortic diameter at the distal edge of the orifice of the most distal preserved branch vessel40of that segment. In most cases, including pre-operative morphology assessment, and as illustrated inFIG.1, the Lowest Preserved Branch Vessel will be the more distal renal artery40.

A third diameter, D3, indicates a Point of Divergence (POD) of the aorta10. The Point of Divergence is defined as the point where the aortic contour changes from a cylindrical or conical shape to a reverse conical shape. In other words, it is the point where the diameter of the aorta10begins to increase (i.e., the walls diverge) in relation to the immediately proximal segment.

A fourth diameter, D4, indicates End of Apposition (EOA). The End of Apposition is defined as the most distal point in the proximal sealing segment where the endograft50still maintains contact with the wall of the aorta10. As such, it is dependent on the diameter of the endograft50used in the repair. For pre-operative assessment, a pre-operative fourth diameter, D4′ (shown inFIG.3), is defined as the point distal to the Point of Divergence where the aortic reaches a threshold diameter. In some embodiments, the threshold diameter is between about 10 mm and about 50 mm, between about 20 mm and about 40 mm, or between about 30 mm and about 35 mm. In one particular exemplary embodiment, the threshold diameter is about 32 mm, as this diameter approximates the maximum sealing diameter of the currently available infrarenal devices. Generally speaking, the fourth diameters D4, D4′ indicate the point where the diameter of the aorta10exceeds a maximum diameter of therapeutic effectiveness of a device used in the treatment of the blood vessel, either theoretical (D4′) or realized (D4).

According to exemplary implementations of the present invention, after receiving or otherwise accessing an image of a blood vessel (e.g., an aorta), the image if analyzed to identify the location of these four points of reference of the blood vessel (D1-D4). The relative locations of these four points (D1-D4) are reduced to three length, or distance, measurements (L1, L3, L4), all based on the location of D2(Lowest Preserved Branch Vessel). The lengths, L1, L3, L4are defined as the longitudinal distance from each respective point of reference to D2. They are expressed as a positive value when the respective point of reference is distal to D2. They are expressed as a negative value when the respective point of reference is proximal to D2. With continued reference toFIG.1, L1is the longitudinal distance of D1(Start of Devices) to D2(Lowest Preserved Branch Vessel); L3is the longitudinal distance of D3(Point of Divergence) to D2(Lowest Preserved Branch Vessel); and L4is the longitudinal distance of D4(End of Apposition) to D2(Lowest Preserved Branch Vessel.) From these seven data points, numerous anatomic characteristics can be calculated or inferred.

As used herein, the Point of Divergence (D3) is considered the boundary marking the distal extent of the normal seal zone and the proximal extent of the aneurysm. This definition was chosen for a number of reasons. First, rather than relying on a subjective evaluation of the sealing adequacy of a vessel segment, it is an objectively defined point. Second, normal vessels are cylindrical or slightly conical in morphology. That is, the diameter of normal vessels gradually decreases from proximal to distal. While a vessel segment is conventionally considered aneurysmal once its diameter reaches 1.5 to 2 times that of a normal vessel, any dilation is abnormal by strict definition. Therefore, it is contended that reverse conical morphology is more appropriately included as part of the aneurysmal disease process rather than as part of the normal proximal segment.

However, it must also be recognized that reverse conical segments within the sealing diameter of the some endografts known in the art can still contribute to the sealing mechanism, even if they are diseased by strictest definition. As used herein, such an interaction is referred to as “Sub-Seal” to differentiate from the more robust sealing interaction in normal cylindrical or conical segments. The Sub-Seal zone extends from the Point of Divergence (D3) to the End of Apposition (D4). Mathematically, the length of this segment can be derived as L4minus L3. It should be noted that the actual length of Sub-Seal achieved is not only dependent on the diameter of endograft but also its positioning in the potential Sub-Seal segment. Therefore, the Sub-Seal length (actual) can be determined mathematically as the lesser of (L4−L3) versus (L4−L1).

Since the term “Seal” as used herein is reserved only for cylindrical or conical segments of the blood vessel, the length of Seal extends from the Start of Devices (D1) to the Point of Divergence (D3) and is expressed mathematically as L3minus L1. The Total Apposition Length (TAL) extends from the Start of the Devices (D1) to the End of Apposition (D4) and is defined as the sum of the Seal and Sub-Seal lengths. It can also be determined mathematically as L4minus L1.

The Seal and the Sub-Seal can be further differentiated by the involvement of branch vessels in their respective aortic segments. Since the presence of such branch vessels requires more complex strategies (such as fenestrated, branched, or parallel grafts) for their preservation during endovascular repair, Seal and Sub-Seal segments proximal to the Lowest Preserved Branch Vessel (D2) are distinguished as “Complex” Seal and Sub-Seal segments. Those segments distal to the lowest preserved branch vessel (D2) can be treated with standard endografts and are therefore distinguished as “Standard” Seal and Sub-Seal segments.

As noted previously, the term “Neck” has historically denoted the infrarenal segment of potential seal in the aorta. As used herein, the term “Neck” is reserved for the portion of the cylindrical or conical potential infra-branch sealing segment and is analogous to Standard Seal. Mathematically, the Neck corresponds to the greater of L3versus zero (since L3will otherwise have a negative value if the Point of Divergence is proximal to the lowest renal artery.)

Referring now toFIGS.2A-2C, the term “Sub-Neck” is analogous to Standard Sub-Seal and denotes the infra-renal portion of the potential Sub-Seal segment and corresponds to the lesser value of (L4-L3) versus L4. Finally, the segment of aneurysm30that is not amenable for Sub-Seal (ie, diameter greater than 32 mm or that of the actual device used) is referred to as the Sac32. For example, as shown inFIG.2A, where the Point of Divergence (D3) is at the same location as the End of Apposition (D4), the aorta10can be said to have only a Neck20and a Sac32. By comparison, as shown inFIGS.2B and2C, where there is space between the Point of Divergence (D3) and the End of Apposition (D4), a Sub-Neck22is also defined in the location between the Point of Divergence (D3) and the End of Apposition (D4).

For completeness, the terminus14of the aorta10is considered D9. The distal extent of the aortic aneurysm30is defined as the point where the aorta10resumes its normal cylindrical or slightly convergent shape and is denoted the Point of Convergence (D8). If the aorta10does not resume a normal contour distally then D8=D9, as shown inFIG.3. Although not expressly shown, in some embodiments of the present invention, an origin of the blood vessel is also identified.

Referring now toFIG.3, in some cases, an aneurysm50takes the shape of a double-bubble or snowman. That is, the contour of the aorta10converges or narrows for a short segment, then diverges a second time prior to converging again. If present, that intervening point of narrowing is referred to as a Point of Restriction (D5.) A segment of potential apposition involving the Point of Restriction (D5), can be considered a Zone of Restriction.

The maximum diameter of the aneurysm50is referred to as D6and the flow lumen at that point referred to as D7. The corresponding lengths of any of these points of reference are similarly determined in relation to D2by convention. It should be noted that the nomenclature is arbitrary and can include additional points of reference such as those of other vessel segments in either an integrated or independent system. Additional characteristics such as the amount of calcification, atheroma, thrombus, dissection, outflow vessels, angulation, etc. can also serve as data points and any combination of data points can be used formulaically to derive additional data points.

Although the terms “zone” and “segment” are often used interchangeably, the term “zone” also implies a specific connotation in terms of anatomic location within the aorta. That is, the Society of Thoracic Surgery has endorsed a numbered zone system that expands on the scheme for the aortic arch originally proposed by Iwinaka to include the remainder of the aorta and into the iliac arteries. The boundaries of the zones are based primarily on the location of the orifice of the important branch vessels of the aorta. Referring still toFIG.3, for the abdominal aorta10, Zone 5 refers to the aortic segment proximal to the celiac artery46. Zone 6 refers to the aortic segment spanning from the proximal edge of the celiac artery46to the proximal edge of superior mesenteric artery44. Zone 7 refers to the aortic segment spanning from the proximal edge of the superior mesenteric artery44to the proximal edge of the most proximal renal artery42. Zone 8 refers to the aortic segment spanning from the proximal edge of the most proximal renal artery42to the distal edge of the of the most distal renal artery40. Zone 9 refers to the aortic segment spanning from the distal edge of the most distal renal artery40to the aortic terminus14.

In accordance with the present invention, and referring now toFIGS.3,4A-4C,5A-5B, and6A-6B, the numbered zones are further subdivided by decimal places to denote an even more specific location in the aortic tree using a single numerical value. For the abdominal aorta10, the numeric midpoint of Zones 6, 7, and 9 are the most distal edge of the celiac46, superior mesenteric44, and inferior mesenteric arteries48respectively. The numerical midpoint of Zone 8 is the most proximal edge of the most distal renal artery40. For data management, the vessels themselves can also be numbered in correspondence to the Zone that they define.

The practical application of using Sub-Zones is that it is possible to infer the clinical relevance of the location of a Point of Reference. For example, defining the location of the Start of Devices (D1) at Sub-Zone 7.3 infers that the devices not only cover both renal arteries40,42(being proximal to Zone 8), but more precisely that it encroaches on the lumen of the Superior Mesenteric Artery44by approximately 40%. Such precise clinically important information cannot be inferred with the current zone system nor by simply knowing the length of L1. Likewise, sub-zones allows inference to the length of the sealing segment, specifically in regards to the location of the Point of Divergence (D3) and the End of Apposition (D4,D4′). For example, a Point of Divergence (D3) location of Sub-Zone 9.0 signifies it is flush to the distal edge of the lowest renal artery40(L3=0). Sub-zone 9.1 refers to the segment from 1-5 mm distal to lowest renal artery40. Sub-zone 9.2 refers to the segment from 6-10 mm distal to lowest renal artery40. Sub-zone 9.3 refers to the segment from 11-15 mm distal to lowest renal artery40. Sub-zone 9.4 refers to segment from 16 mm distal to lowest renal artery40to the inferior mesenteric artery48. While in this instance more precise information is available from the L3and L4measurements, the practical application of this Sub-zone division is that it allows for grouping of similar anatomic morphologies for comparative purposes using more objective criteria than is currently available. In this system, it is proposed that a Point of Divergence (D3) location of Sub-zone 9.0 infers “Juxtarenal” morphology, Sub-zone 9.1 infers an “Ultra-short” neck, Sub-zone 9.2 infers a “Short” neck, Sub-zone 9.3 infers and “Moderate” neck, and Sub-zone 9.4 infers a “Long” neck. Of course, such definitions can be modified, for example depending on the results of outcomes research, without departing from the spirit and scope of the present invention.

Referring now specifically toFIGS.4A-4C, it is recognized that aberrant branch vessel anatomy poses significant challenges to any Aortic Zone nomenclature. The most common variants involve the renal arteries, but any branch vessel can exhibit aberrancy. Any contingency for aberrancy should preferably be consistent with the principals of the original zone system. For the common scenario of accessory renal arteries within the vicinity of a normal zone 8, in accordance with the present invention, a second decimal point is added to clarify both the location and total number of renal arteries.

For example, as shown inFIG.4A, the most proximal renal artery42is identified by the nomenclature 8.00 (L) and the most distal renal artery40is identified by the nomenclature 8.5 (R). Similarly, as shown inFIG.4B, in which there is one accessory renal artery, the most proximal renal artery42is identified by the nomenclature 8.00 (R), the intermediate renal artery41is identified by the nomenclature 8.33 (L), and the most distal renal artery40is identified by the nomenclature 8.67 (R). Similarly, as shown inFIG.4C, in which there are two accessory renal arteries, the most proximal renal artery42is identified by the nomenclature 8.00 (R), the proximal intermediate renal artery43is identified by the nomenclature 8.25 (L), the distal intermediate renal artery41is identified by the nomenclature 8.50 (R), and the most distal renal artery40identified by the nomenclature 8.75 (L). As shown inFIGS.4A-4Cas compared toFIG.3, no changes are made to the nomenclature relating to the superior mesenteric artery44or the celiac artery46or the corresponding zones.

Referring now specifically toFIGS.5A and5B, if an accessory renal artery41arises proximal to the superior mesenteric artery44, distal to the inferior mesenteric artery48, or clearly within an infra-renal aneurysm sac, then the location of the accessory renal artery41is assigned to the corresponding zone if it weren't present. For example, as shown inFIG.5A, in which the accessory renal arises41is proximal to the superior mesenteric artery44, the accessory renal artery41is identified by the nomenclature 6.5 (L). Likewise, as shown inFIG.5B, in which the accessory renal arises41is distal to the inferior mesenteric artery48, the accessory renal artery41is identified by the nomenclature 9.5 (R).

Referring now specifically toFIGS.6A and6B, in the absence of accessory renal arteries, the true aberrancy of a main renal artery would warrant a remapping of the Zones. For example, as shown inFIG.6A, in which the most proximal renal artery42is proximal to the superior mesenteric artery44, the most proximal renal artery42is identified by the nomenclature 6.5 (L). Likewise, as shown inFIG.6B, in which the most distal renal artery40is distal to the inferior mesenteric artery48, the most distal renal artery40is identified by the nomenclature 9.5 (R).

Of course, the above examples are non-limiting and a person of ordinary skill would readily understand how to apply the numbered zone system of the present invention to a variety of anatomical situations.

Referring now toFIGS.7,8,9A-9B, and10A-10B, another advantage of reducing the anatomy to Points of Reference is that specific anatomies can be characterized by the order of such reference points. In this system, each anatomy is grouped into a specific phenotype based on the order of the Points of Reference. The Baseline Phenotypes (prior to repair) are based on the order of the Lowest Preserved Branch Vessel (D2), the Point of Divergence (D3), and the End of Apposition (D4′). In particular, the classification of the aneurysm includes determining which of the seal zone, sub-seal zone, and aneurysm sac contains the Lowest Preserved Branch Vessel. Since baseline sealing characteristics are best defined by the aortic segment immediately distal to the Lowest Preserved Branch Vessel (D2), the classification will default to the inferior phenotype when the location of D2is the same as D3or D4′. It is assumed that for an aorta10with an aneurysm30, D4′ must be distal to D3, as shown inFIG.7,

Mathematically, there are three sequences that satisfy this assumption. The Baseline Phenotypes are based on these three sequences. As shown inFIG.8, Phenotype A is based on the sequence D2>D3>D4′ moving distally along the aorta10. In other words, the Lowest Preserved Branch Vessel (D2) is proximal to both the Point of Divergence (D3) and the End of Apposition (D4′).

Phenotype A is most favorable phenotype. In the typical case where the Lowest Preserved Branch Vessel is the lowest renal artery40, Phenotype A contains an infrarenal Standard Seal zone (Neck)20and its ensuing potential Standard Sub-Seal zone (Sub-Neck)22. Conceptually, this phenotype is most associated with standard infrarenal endovascular aneurysm repair.

As shown inFIGS.9A and9B, Phenotype B is based on the sequence D3>D2>D4′ moving distally along the aorta10. In other words, the Lowest Preserved Branch Vessel (D2) is at to the Point of Divergence (D3) (FIG.9A) or distal to the Point of Divergence (D3) (FIG.9B) but proximal to the End of Apposition (D4′).

Phenotype B is the second most favorable phenotype. Returning to the typical case where the Lowest Preserved Branch Vessel is the lowest renal artery40, Phenotype B does not contain an infrarenal Standard Seal zone (Neck), but does contain a potential Standard Sub-Seal zone (Sub-Neck)22. Conceptually, standard infrarenal endovascular repair may still be appropriate if L4is long. Otherwise, complex repair is likely required for long-term durability.

As shown inFIGS.10A and10B, Phenotype C is based on the sequence D3>D4′>D2moving distally along the aorta10. In other words, the Lowest Preserved Branch Vessel (D2) is at the End of Apposition (D4′) (FIG.10A) or distal to the End of Apposition (D4′) (FIG.10B).

Phenotype C is the least favorable phenotype. There is no potential sealing segment immediately distal to the Lowest Preserved Branch Vessel (e.g, the lowest renal artery40). Conceptually, complex repair is required for exclusion of the aneurysm in this phenotype.

For convention, the presence of a Point of Restriction (D5) is denoted by adding “Plus” to the phenotype nomenclature to recognize the additional potential apposition zone. For example, a Point of Restriction (D5) in Phenotype B anatomy would be considered Phenotype B Plus (or B+) anatomy.

After repair, each baseline phenotype is subdivided based on the relative location of the Start of Devices (D1). The subdivision represents a crude numeric sealing score, where higher numbers denote the incorporation of more sealing segments and a subdivision of “0” denotes the absence of apposition. It should also be recognized that the location of the potential End of Apposition (D4′) used in determining baseline phenotype is based on a theoretical maximum sealing diameter. The actual End of Apposition (D4) achieved with repair can differ significantly from D4′ depending on the size and shape of the device used for repair. As such, while the potential End of Apposition (D4′) should be distal to the Point of Divergence (D3), the same is not always true for the actual End of Apposition (D4). In many cases, the difference in location between D4and D4′ has minimal impact to the overall sealing effectiveness of the configuration as long as End of Apposition (D4) is distal to the Lowest Preserved Branch Vessel (D2); and, therefore, should not warrant a reclassification of the baseline phenotype. This is denoted in mathematic shorthand with a comma. Finally, the classification will default to the inferior subdivision when the location of D1is the same as D2or D3.

Referring now toFIG.11, Sub-phenotype A3is based on the sequence D1>D2>D3, D4. In other words, the Start of Devices (D1) is proximal to the Lowest Preserved Branch Vessel (D2), which in turn is proximal to both the Point of Divergence (D3) and the End of Apposition (D4.) This sub-phenotype is the most secure in terms of sealing effectiveness. It likely involves three sealing segments (or two long ones), including the Complex Seal segment, the Seal segment, and usually the Sub-Seal segment.

Referring now toFIG.12, Sub-phenotype A2is based on the sequence D2>D1>D3, D4. In other words, the Start of Devices (D1) is at (FIG.12A) or distal to (FIG.12B) the Lowest Preserved Branch Vessel (D2), but is proximal to both the Point of Divergence (D3) and the End of Apposition (D4.) This sub-phenotype likely involves two sealing segments (or one long one), including the Seal segment, and usually the Sub-Seal segment.

Referring now toFIGS.13A and13B, Sub-phenotype A1is based on the sequence D2>D3>D1>D4. In other words, the Start of Devices (D1) is distal to the Lowest Preserved Branch Vessel (D2), at (FIG.13A) or distal to (FIG.13B) the Point of Divergence, but is proximal to the End of Apposition (D4.) This sub-phenotype involves only one sealing segment, the Sub-Seal segment.

Referring now toFIG.14, Sub-phenotype A0is based on the sequence D2>D3>D4′>D1. In other words, since there is no achieved apposition, the Start of Devices (D1) is distal to the Lowest Preserved Branch Vessel (D2), the Point of Divergence (D3), and the potential End of Apposition (D4′.) This sub-phenotype generally indicates a slipped or undersized endograft.

Referring now toFIG.15, Sub-phenotype B3is based on the sequence D1>D3>D2>D4. In other words, the Start of Devices (D1) is proximal to the Point of Divergence (D3), the Lowest Preserved Branch Vessel (D2), and the End of Apposition (D4.) This sub-phenotype likely involves three sealing segments, including the Complex Seal segment, the Complex Sub-Seal segment (if one exists), and the Sub-Seal segment.

Referring now toFIGS.16A and16B, Sub-phenotype B2is based on the sequence D3>D1>D2>D4. In other words, the Start of Devices (D1) is at (FIG.16A) or distal to (FIG.16B) the Point of Divergence (D3), but proximal to the Lowest Preserved Branch Vessel (D2), and the End of Apposition (D4.) This sub-phenotype involves two sealing segments, including the Complex Sub-Seal segment, and the Sub-Seal segment.

Referring now toFIGS.17A and17B, Sub-phenotype B1is based on the sequence D3>D2>D1>D4. In other words, the Start of Devices (D1) is at (FIG.17A) or distal to (FIG.17B) both the Point of Divergence (D3) and the Lowest Preserved Branch Vessel (D2), but proximal to the End of Apposition (D4.) Similar to A1, this sub-phenotype involves only one sealing segment, the Sub-Seal segment.

Referring now toFIG.18, Sub-phenotype B0is based on the sequence D3>D2>D4′>D1. In other words, since there is no achieved apposition, the Start of Devices (D1) is distal to the Point of Divergence (D3), the Lowest Preserved Branch Vessel (D2), and the potential End of Apposition (D4′.) Similar to A0, this sub-phenotype generally indicates a slipped or undersized endograft.

Since baseline Phenotype C entails only two potential sealing segments, there is no Sub-phenotype C3. Referring now toFIG.19, Sub-phenotype C2is based on the sequence D1>D3, D4>D2. In other words, the Start of Devices (D1) is proximal to both the Point of Divergence (D3) and the End of Apposition (D4), which in turn are proximal to the Lowest Preserved Branch Vessel (D2), This sub-phenotype likely involves two sealing segments, including the Complex Seal segment, and usually the Complex Sub-Seal segment.

Referring now toFIGS.20A and20B, Sub-phenotype C1is based on the sequence D3>D1>D4>D2. In other words, the Start of Devices (D1) is at (FIG.20A) or distal to (FIG.20B) the Point of Divergence (D3), but proximal to the the End of Apposition (D4), which in turn is at or proximal to the Lowest Preserved Branch Vessel (D2). This sub-phenotype involves only one sealing segment, the Complex Sub-Seal segment.

Referring now toFIG.21, Sub-phenotype C0is based on the sequence D3>D1<D4′>D2. In other words, since there is no achieved apposition, the Start of Devices (D1) is distal to the Point of Divergence (D3), and the potential End of Apposition (D4′), which in turn is at or proximal to the Lowest Preserved Branch Vessel (D2), Similar to A0and B0, this sub-phenotype generally indicates a slipped or undersized endograft.

For clarification, since the Start of Devices (D1) is defined as the most proximal end of the fabric covered portion of the main aortic endograft that is at least partially apposed to the wall of the aorta, the D1of an undersized graft with no apposition to the wall of the aorta is considered distal to the potential End of Apposition (D4′) regardless of whether or not the device has physically slipped.

Further, as noted previously, the actual End of Apposition (D4) achieved with repair can differ significantly from D4′ depending on the size and shape of the device used for repair. In particular, as shown for example inFIG.22B, bifurcated devices taper as they transition from the cylindrical main body portion to split into two smaller limbs. The length of the cylindrical main body portion proximal to the transition varies from device to device. Even the shortest main body devices are designed to be of sufficient length to achieve adequate apposition to the wall of the aorta in straightforward anatomy. In most cases then, including some complex repairs, any “unrealized” apposition is related to the presence of a relatively long potential seal zone and will not compromise the effectiveness of the device to vessel sealing interaction. Therefore, a reclassification of the sub-phenotype is not indicated and so the repairs shown inFIGS.22A and22Bare both categorized as Sub-phenotype A3.

However, in other cases, the use of a shorter main body device or a tapered cylindrical device can have a significant deleterious impact on the effectiveness of the device to vessel sealing interaction. Specifically, compromise can occur when the use and positioning of such devices unnecessarily places the End of Apposition (D4) proximal to the Lowest Preserved Branch Vessel (D2).

Perhaps this scenario is best illustrated in complex repairs utilizing parallel endografts with reference now toFIGS.23A and23B. Since standard parallel endograft configurations entail a sealing segment with at least two essentially cylindrical devices alongside each other, there is an inherent mismatch between the overall shape of the aggregate device configuration and the shape of the aorta in these segments. This mismatch often results in gaps in apposition between the combined devices and the wall of the aorta known as gutters, leaving the potential for an endoleak and continued pressurization of the aneurysmal sac. However, the recruitment of an additional sealing segment distal to the Lowest Preserved Branch Vessel (D2) with circumferential apposition provides a barrier against the transmission of any endoleak from the more proximal complex sealing segments to the aneurysm sac. Therefore, it is important in the sub-phenotypes A3, B3, and B2that the apposition of the device extends distal to the Lowest Preserved Branch Vessel (D2) to include that additional barrier of circumferential apposition, as shown inFIG.23A. If the apposition does not extend distal enough to include the potential sealing segments distal to the Lowest Preserved Branch Vessel (D2), then the apposition pattern is functionally similar to that of the C phenotype and the repair should be re-classified as the C′ phenotype to reflect that, as illustrated inFIG.23B. Sub-phenotypes A3and B3should be reclassified to the C′2sub-phenotype. Sub-phenotype B2should be reclassified to the C′1sub-phenotype.

Unfortunately, although the utility of parallel endografting techniques for challenging anatomy in high risk patients has been established in the scientific literature, there are no currently available FDA approved devices designed specifically for parallel endografts and very little consensus as to protocols for their use. While it is intuitive that more overlap in the complex sealing segments can reduce the chance for gutter leaks, aggressive positioning of a shorter main body device designed for infrarenal anatomy may inadvertently lead to placement of the End of Apposition proximal to the Lowest Preserved Branch Vessel as described above.

In this sense, the described Points of Reference system cannot only provide a classification for outcomes research, it can also provide a framework for planning and determining indications for repair when considering the various options available. In particular, the classification of the of the aneurysm as described above can be used to determine which device, or devices, should be implanted within the blood vessel for treatment of the aneurysm. To avoid the issue of reclassification to the much less robust C′ phenotype, one must first recognize the presence and importance of non-traditional sealing segments such as the Sub-Neck. Shorter main body endografts can still be used in a manner to include these segments by deploying the device low enough to recruit these segments, then extending their cylindrical portion proximally with an aortic extension cuff to provide adequate overlap in the complex apposition zones. Alternatively, the extension cuff can be deployed first to achieve apposition in the infra-branch segment and then extended proximally with the main body device, known as a Kilt technique. Regardless of the anatomic complexity, the goal of the repair should be to extend proximal to the Point of Divergence (D3) if at all feasible without excessive risk.

A Point of Restriction (D5), if present, likewise represents another key area of potential apposition, especially in Phenotype B+ and C+ anatomy. Similar strategies to incorporate the apposition zone of a Point of Restriction (D5), such as longer main body endografts or the Kilt technique, would be apropos in these instances as well.

Referring now toFIGS.24A and24B, another principal based on this system that may help maintain barriers to endoleaks is to minimize the number of parallel grafts that cross the Point of Divergence (D3) and the End of Apposition (D4), as illustrated inFIG.24A. As noted previously, the circumferential apposition present when these points are distal to a branch vessel preserved with a parallel endograft can prevent the transmission of any gutter leak to the aneurysm sac. Certainly, when the Point of Divergence (D3) is distal (indicating a more secure protective segment of standard seal), the chance of successful exclusion should be high. In phenotype C, there is no apposition distal to the Lowest Preserved Branch Vessel, but there may be potential apposition distal to any other preserved branch vessel. If the Lowest Preserved Branch Vessel is preserved in antegrade fashion, then it will need to cross D3and D4and potentially compromise the barriers that are protecting the sac from any gutter leaks related to the more proximal preserved branch vessels. Treatment of any endoleak from this compromise may necessitate proximal extension of the devices into aortic segments with other branch vessels, further adding complexity to case and the risk of complications. If instead, the lowest branch vessel is preserved in retrograde fashion, as shown inFIG.24B, then an external portion of a parallel branch stent of the parallel endograft will not cross D3or D4. When considered singularly, the more proximal preserved vessels are now treated with the more secure equivalent of an A3, B3, or B2sub-phenotype. The Lowest Preserved Branch Vessel still proposes a risk for endoleak, but it can likely be treated more easily by isolating its seal mechanism from other preserved branch vessels. Multiple treatment options can be used, but one that relies on parallel endografts involves a sandwich technique. In this technique, the parallel stents are contained (or sandwiched) within the lumen of another device rather than a vessel such as the aorta. The parent device is deployed first and establishes a prosthetic sealing segment that was not otherwise present in the native anatomy.

Referring now toFIGS.25A and25B, in phenotype B, there is no Seal distal to the Lowest Preserved Branch Vessel, but there is Sub-Seal. If the Lowest Branch Vessel is preserved using an antegrade parallel graft, as shown inFIG.25A, then an external portion of a parallel branch stent of the parallel endograft will necessitate crossing the Point of Divergence (D3), compromising the seal segment. While it appears that retrograde preservation will similarly necessitate crossing the End of Apposition (D4), any compromise can be avoided using the sandwich technique, as shown inFIG.25B, by positioning the sealing end of the parent device within the sub-seal segment. Since the parallel grafts are subsequently positioned within the prosthetic sealing segment internal to the parent device, there is no functional crossing of the End of Apposition. The transition point where the parallel grafts are now contained within the parent device will be defined as the Point of Internalization.

Although the above discussion was focused on aneurysms of the aorta, the Points of Reference system can be adapted to any other blood vessel or other segments of the aorta. As an example, for descending thoracic aortic aneurysms, the renovisceral vessels now become relevant to the distal sealing segment of the repair. Point of Divergence is replaced with the Point of Convergence and the sealing complexity is now reversed, increasing as the End of Devices moves distally and the Highest Preserved Branch Vessel becoming the focal point.

In some embodiments of the present invention, the above-described methods for classification are preferably achieved through the use of a digital computer program (i.e., computer-readable instructions executed by a processor of a computer) that includes appropriate modules for executing the requisite instructions (which are stored in a memory component or similar computer-readable medium). Thus, an exemplary system for anatomic classification of blood vessel anatomy in aneurysms in accordance with the present invention may also be characterized as including: (a) a data receiving module for receiving an image of a blood vessel; and (b) an analysis module for (i) analyzing the image to identify a point of divergence of the blood vessel and one or more additional points of reference of the blood vessel, (ii) measuring one or more distances between the point of divergence of the blood vessel and at least one of the one or more additional points of reference, and (iii) classifying the aneurysm based upon the measured distances

Preliminary studies utilizing the Point of Reference system for outcomes research has yielded some important early findings. First, it appears that late proximal neck failures occur predominantly when the Start of Devices (D1) is distal to the Point of Divergence (D3). Even cases with seemingly favorable infrarenal anatomy due to the presence of a Point of Restriction (D5) in the subseal zone (i.e., Phenotype B+ or C+ anatomy) are prone to late failure if the Start of Devices (D1) is not extended proximal to the Point of Divergence (D3). Further, the location of the Point of Divergence (D3) in relation to the renal and visceral branch vessels (i.e., specific aortic zone) does not change over time. In other words, the segments of the aorta at high risk for degeneration can be identified very early in the disease process using the Point of Reference system.

These early findings indicate that the Point of Divergence (D3) is an exceptionally important boundary parameter for long term success in endovascular aneurysm repair and that treatment strategies, including the design of devices, should aim to extend the repair proximal to the Point of Divergence. Device specific modifications, such as the addition of branches or fenestrations, are one way to achieve this goal. A modular system, such as one that utilizes parallel endografts, is another potential method.

The other components of the Point of Reference system have relevance to treatment strategies and device designs as well. As alluded to previously, the Point of Reference system can help guide appropriate parallel graft configurations to avoid crossing the Point of Divergence (D3) and/or the End of Apposition (D4) with the externalized portion of the parallel graft. Extending the main body of an aortic graft with strategies such as the Kilt technique can sometimes be important to recruit apposition at the Point of Divergence (D3) or a Point of Restriction (D5) in both device specific and modular designs. These are just some examples of how the Point of Reference system can be used to target therapies.

While the terms used herein are believed to be well understood by those of ordinary skill in the art, certain definitions are set forth to facilitate explanation of the presently-disclosed subject matter.

Unless defined otherwise, all technical and scientific terms used herein have the same meaning as is commonly understood by one of skill in the art to which the invention(s) belong.

All patents, patent applications, published applications and publications, GenBank sequences, databases, websites and other published materials referred to throughout the entire disclosure herein, unless noted otherwise, are incorporated by reference in their entirety.

Where reference is made to a URL or other such identifier or address, it understood that such identifiers can change and particular information on the internet can come and go, but equivalent information can be found by searching the internet. Reference thereto evidences the availability and public dissemination of such information.

As used herein, the abbreviations for any protective groups, amino acids and other compounds, are, unless indicated otherwise, in accord with their common usage, recognized abbreviations, or the IUPAC-IUB Commission on Biochemical Nomenclature (see, Biochem. (1972) 11(9):1726-1732).

Although any methods, devices, and materials similar or equivalent to those described herein can be used in the practice or testing of the presently-disclosed subject matter, representative methods, devices, and materials are described herein.

The present application can “comprise” (open ended) or “consist essentially of” the components of the present invention as well as other ingredients or elements described herein. As used herein, “comprising” is open ended and means the elements recited, or their equivalent in structure or function, plus any other element or elements which are not recited. The terms “having” and “including” are also to be construed as open ended unless the context suggests otherwise.

Following long-standing patent law convention, the terms “a”, “an”, and “the” refer to “one or more” when used in this application, including the claims. Thus, for example, reference to “a cell” includes a plurality of such cells, and so forth.

Unless otherwise indicated, all numbers expressing quantities of ingredients, properties such as reaction conditions, and so forth used in the specification and claims are to be understood as being modified in all instances by the term “about”. Accordingly, unless indicated to the contrary, the numerical parameters set forth in this specification and claims are approximations that can vary depending upon the desired properties sought to be obtained by the presently-disclosed subject matter.

As used herein, the term “about,” when referring to a value or to an amount of mass, weight, time, volume, concentration or percentage is meant to encompass variations of in some embodiments ±20%, in some embodiments ±10%, in some embodiments ±5%, in some embodiments ±1%, in some embodiments ±0.5%, in some embodiments ±0.1%, in some embodiments ±0.01%, and in some embodiments ±0.001% from the specified amount, as such variations are appropriate to perform the disclosed method.

As used herein, ranges can be expressed as from “about” one particular value, and/or to “about” another particular value. It is also understood that there are a number of values disclosed herein, and that each value is also herein disclosed as “about” that particular value in addition to the value itself. For example, if the value “10” is disclosed, then “about 10” is also disclosed. It is also understood that each unit between two particular units are also disclosed. For example, if 10 and 15 are disclosed, then 11, 12, 13, and 14 are also disclosed.

As used herein, “optional” or “optionally” means that the subsequently described event or circumstance does or does not occur and that the description includes instances where said event or circumstance occurs and instances where it does not. For example, an optionally variant portion means that the portion is variant or non-variant.

It will be understood that various details of the presently disclosed subject matter can be changed without departing from the scope of the subject matter disclosed herein. Furthermore, the foregoing description is for the purpose of illustration only, and not for the purpose of limitation.