PCSK9 Inhibitors in Heart Transplant Patients: Safety, Efficacy, and Angiographic Correlates.

BACKGROUND: Statins are recommended in heart transplant patients, but are sometimes poorly tolerated. Alternative agents are often considered including proprotein convertase subtilisin/kexin type-9 inhibitors (PCSK9i). We sought to investigate the use of PCSK9i after heart transplantation. METHODS AND RESULTS: We identified patients who received a heart transplant from 1999 to 2019 and were started on PCSK9i at our institution. Clinical, laboratory, and coronary angiography with intravascular ultrasound results were compared. Among 65 patients initiated on PCSK9i (48 for statin intolerance and 17 for refractory hyperlipidemia), the median time from transplant was 5.5 years (interquartile range [IQR], 2.8-9.9 years) with a median PCSK9 treatment duration of 1.6 years (IQR, 0.8-3.2 years) and 80% still on treatment. Evolocumab was used in 73.8%, alirocumab in 12.3%, and both in 13.8% owing to insurance coverage. All patients required prior authorization; initial denial occurred in 18.5% and 32.3% had denials in subsequent years. The median low-density lipoprotein cholesterol decreased from 130 mg/dL (IQR, 102-148 mg/dL) to 55 mg/dL (IQR, 35-74 mg/dL) after starting PCSK9i (P < .001), with 72% of patients achieving a low-density lipoprotein cholesterol of <70 mg/dL after treatment. There were also significant reductions of total cholesterol, non-high-density lipoprotein cholesterol, total/high-density lipoprotein cholesterol ratio, and triglycerides, with a modest increase in high-density lipoprotein cholesterol. These changes were durable at latest follow-up. In 33 patients with serial coronary angiography and intravascular ultrasound, PCSK9i were associated with stable coronary plaque thickness and lumen area. CONCLUSIONS: Among heart transplant recipients, PCSK9i are effective in lowering cholesterol levels and stabilizing coronary intimal hyperplasia with minimal side effects. Despite favorable effects, access and affordability remain a challenge.

Single-center utilization of donor-derived cell-free DNA testing in the management of heart transplant patients.

BACKGROUND: Gene expression profiling (GEP) and donor-derived cell-free DNA (dd-cfDNA) are useful in acute rejection (AR) surveillance in orthotopic heart transplant (OHT) patients. We report a single-center experience of combined GEP and dd-cfDNA testing for AR surveillance. METHODS: GEP and dd-cfDNA are tested together starting at 2 months post-OHT. After 6 months, combined testing was obtained before scheduled endomyocardial biopsy (EMB), and EMB was canceled with a negative dd-cfDNA. This approach was compared to using a GEP-only approach, where EMB was canceled with a negative GEP. We evaluated for frequency of EMB cancellation with dd-cfDNA usage. RESULTS: A total of 153 OHT patients over a 13-month period underwent 495 combined GEP/dd-cfDNA tests. 82.2% of dd-cfDNA tests were below threshold. Above threshold results identified high-risk patients who developed AR. 378 combined tests ≥6 months post-OHT resulted in cancellation of 83.9% EMBs as opposed to 71.2% with GEP surveillance alone. There were 2 acute cellular and 2 antibody-mediated rejection episodes, and no significant AR ≥6 months. CONCLUSION: Routine dd-cfDNA testing alongside GEP testing yielded a significant reduction in EMB volume by re-classifying GEP (+) patients into a lower risk group, without reduction in AR detection. The addition of dd-cfDNA identified patients at higher risk for AR.

Influence of Donor Transmitted and Rapidly Progressive Coronary Vascular Disease on Long-Term Outcomes After Heart Transplantation: A Contemporary Intravascular Ultrasound Analysis.

BACKGROUND: Donor-transmitted atherosclerosis (DTA) and rapidly progressive cardiac allograft vasculopathy (CAV) at 1 year are intravascular ultrasound (IVUS)-derived measures shown to predict adverse cardiovascular outcomes in the setting of early generation immunosuppressive agents. Given the paucity of data on the prognostic value of IVUS-derived measurements in the current era, we sought to explore their association with adverse outcomes after heart transplantation. METHODS AND RESULTS: This is a retrospective cohort analysis of patients who underwent heart transplantation at our center between January 2009 and June 2016 with baseline and 1-year IVUS. Five IVUS sections were prospectively analyzed for intimal thickness and lumen area. DTA was defined as maximum intimal thickness of 0.5 mm or greater at baseline, and rapidly progressive CAV as an increase in maximum intimal thickness by 0.5 mm or more at 1 year. Our primary analysis assessed the relationship of IVUS and other clinical data on a composite outcome: coronary intervention, CAV stage 2 or 3 (defined by the International Society for Heart and Lung Transplantation 2010 nomenclature), or cardiovascular death. Among 249 patients (mean age 51.0 ± 12.2 years and 74.3% male) included in the analysis, DTA was detected in 118 patients (51.4%). Over a median follow-up of 6.1 years (interquartile range 4.2-8.0 years), 45 patients met the primary end point (23 percutaneous coronary intervention, 11 CAV 2 or 3, and 11 cardiovascular deaths as first event). DTA and rapidly progressive CAV were not associated with the primary end point, all-cause mortality, or retransplantation. In an additional analysis including post-transplant events, incident rejection was strongly associated with poor outcomes, although cytomegalovirus infection was not. CONCLUSIONS: In this contemporary cohort, IVUS-derived DTA and rapidly progressive CAV were not associated with medium- to long-term adverse events after heart transplantation.

Transcarotid Versus Transapical and Transaortic Access for Transcatheter Aortic Valve Replacement.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) using transcarotid access may improve outcomes compared with transapical or transaortic access. METHODS: This study retrospectively evaluated 165 patients who were undergoing alternate access TAVR using transcarotid (n = 84), transapical (n = 48), and transaortic (n = 33) access. The 30-day outcomes and 2-year Kaplan-Meier survival were analyzed using a multivariable Cox proportional hazards model. RESULTS: The median Society of Thoracic Surgeons predicted risk of mortality was similar among patients treated by transcarotid, transapical, and transaortic access (9.0% [interquartile range (IQR), 6.6, 12.0] vs 9.1% [IQR, 7.0, 11.7] vs 10.0% [IQR, 8.5, 13.0]; p = 0.14), respectively. Patients treated with transcarotid TAVR had a trend toward lower 30-day mortality (3.6% [3 of 84] vs 6.3% [3 of 48] vs 15.2% [5 of 33]; p = 0.09) and significantly better 2-year survival (88.4% vs 79.2% vs 63.6%; p = 0.004) compared with patients treated by transapical and transaortic access, respectively. In addition, transcarotid access was associated with a shorter median length of stay (3.0 days [IQR, 2.0, 5.0] vs 6.5 days [IQR. 5.0, 9.5] vs 7.0 days [IQR, 5.0, 9.0]; p < 0.001), lower transfusion rate (4.8% [4 of 84] vs 12.0% [12 of 48] vs 24.2% [8 of 33]; p < 0.001), higher likelihood of discharge to home without home health care (89.3% [75 of 84] vs 54.2% [26 of 48] vs 42.4% [14 of 33]; p < 0.001), and similar 30-day stroke rates (2.4% [2 of 84] vs 2.1% [1 of 48] vs 3.0% [1 of 33];p = 0.9). CONCLUSIONS: Transcarotid compared with transapical and transaortic access for TAVR is associated with shorter length of stay, fewer transfusions, more frequent discharge to home, and better 2-year survival.

Bioprosthetic Valve Fracture Improves the Hemodynamic Results of Valve-in-Valve Transcatheter Aortic Valve Replacement.

BACKGROUND: Valve-in-valve (VIV) transcatheter aortic valve replacement (TAVR) may be less effective in small surgical valves because of patient/prosthesis mismatch. Bioprosthetic valve fracture (BVF) using a high-pressure balloon can be performed to facilitate VIV TAVR. METHODS AND RESULTS: We report data from 20 consecutive clinical cases in which BVF was successfully performed before or after VIV TAVR by inflation of a high-pressure balloon positioned across the valve ring during rapid ventricular pacing. Hemodynamic measurements and calculation of the valve effective orifice area were performed at baseline, immediately after VIV TAVR, and after BVF. BVF was successfully performed in 20 patients undergoing VIV TAVR with balloon-expandable (n=8) or self-expanding (n=12) transcatheter valves in Mitroflow, Carpentier-Edwards Perimount, Magna and Magna Ease, Biocor Epic and Biocor Epic Supra, and Mosaic surgical valves. Successful fracture was noted fluoroscopically when the waist of the balloon released and by a sudden drop in inflation pressure, often accompanied by an audible snap. BVF resulted in a reduction in the mean transvalvular gradient (from 20.5±7.4 to 6.7±3.7 mm Hg, P<0.001) and an increase in valve effective orifice area (from 1.0±0.4 to 1.8±0.6 cm2, P<0.001). No procedural complications were reported. CONCLUSIONS: BVF can be performed safely in small surgical valves to facilitate VIV TAVR with either balloon-expandable or self-expanding transcatheter valves and results in reduced residual transvalvular gradients and increased valve effective orifice area.

Bioprosthetic Valve Fracture to Facilitate Transcatheter Valve-in-Valve Implantation.

BACKGROUND: Valve-in-valve transcatheter aortic valve replacement is less effective in small surgical bioprostheses. We evaluated the feasibility of bioprosthetic valve fracture with a high-pressure balloon to facilitate valve-in-valve transcatheter aortic valve replacement. METHODS: In vitro bench testing on aortic tissue valves was performed on 19-mm and 21-mm Mitroflow (Sorin, Milan, Italy), Magna and Magna Ease (Edwards Lifesciences, Irvine, CA), Trifecta and Biocor Epic (St. Jude Medical, Minneapolis, MN), and Hancock II and Mosaic (Medtronic, Minneapolis, MN). High-pressure balloons Tru Dilation, Atlas Gold, and Dorado (C.R. Bard, Murray Hill, NJ) were used to determine which valves could be fractured and at what pressure fracture occurred. RESULTS: Mitroflow, Magna, Magna Ease, Mosaic, and Biocor Epic surgical valves were successfully fractured using high-pressures balloon 1 mm larger than the labeled valve size whereas Trifecta and Hancock II surgical valves could not be fractured. Only the internal valve frame was fractured, and the sewing cuff was never disrupted. Manufacturer's rated burst pressures for balloons were exceeded, with fracture pressures ranging from 8 to 24 atmospheres depending on the surgical valve. Testing further demonstrated that fracture facilitated the expansion of previously constrained, underexpanded transcatheter valves (both balloon and self-expanding) to the manufacturer's recommended size. CONCLUSIONS: Bench testing demonstrates that the frame of most, but not all, bioprosthetic surgical aortic valves can be fractured using high-pressure balloons. The safety of bioprosthetic valve fracture to optimize valve-in-valve transcatheter aortic valve replacement in small surgical valves requires further clinical investigation.

The Descending Thoracic Aorta: Forgotten Vascular Access for Endovascular Device Delivery.

Vascular access for large endovascular devices has evolved as patients have become more complicated and device indications have expanded. As the benefits of catheter-based treatments for aortic aneurysm repair and aortic valve replacement become mainstream, there is a need to address difficult vascular access by developing not only smaller-diameter devices but also creative options for vascular access. We describe direct descending thoracic aortic access during endovascular aneurysm repair, transcatheter aortic valve replacement, and redo mesenteric revascularization in three patients who did not have traditional access options.

Combined Transcatheter Aortic Valve Replacement and Thoracic Endovascular Aortic Repair Using Transapical Access.

Vascular complications remain an important consideration when selecting access for delivery of large endovascular devices. With the advent of transcatheter aortic valve replacement, transapical access has become an acceptable technique when transfemoral or direct transaortic access is contraindicated. We report the use of the transapical approach during thoracic aortic endovascular repair in 2 patients, one of which included concomitant delivery of a transcatheter aortic valve replacement device. To our knowledge, this is the first reported case of a hybrid single-stage transcatheter aortic valve replacement and thoracic aortic endovascular repair using transapical access.

Recurrent Primary Cardiac Sarcoma Managed With Radical Cardiac Resection and Pneumonectomy.

Primary cardiac tumors are extremely rare. Although complete surgical resection of malignant primary cardiac tumors results in an improved survival compared with no intervention, the overall prognosis is generally poor, with treatable recurrent primary cardiac sarcomas being extremely rare. We report a patient with a recurrent primary cardiac sarcoma obstructing the left atrium managed with radical cardiac resection, including right pneumonectomy, with 21-month postprocedural survival.

Do not bite the hand that feeds you.

Radial artery pseudoaneurysms occur infrequently and are most commonly associated with medical interventions such as arterial lines or cardiac catheterization procedures. Animal bites, particularly cat bites, as a cause for radial artery pseudoaneurysms are extremely rare with only 1 previously reported case in the literature. A unique case of digital micro emboli from a radial artery pseudoaneurysm caused by a cat bite to the wrist is presented.

Tailored endovascular repair of traumatic aortic disruptions with "stacked" abdominal aortic extension cuffs.

OBJECTIVE: The management paradigm for traumatic aortic disruptions has evolved from open to endovascular repair. Thoracic stent grafts designed to treat aneurysmal disease, however, have disadvantages, including size mismatch in younger trauma patients and current standard lengths, which may needlessly necessitate coverage of at least 10 cm of thoracic aorta, increasing the risk of spinal cord ischemia. The "off-label" use of abdominal aortic extension cuffs to treat traumatic aortic disruptions may provide an advantage in this regard by better size matching for the younger trauma patient, reduced thoracic aortic coverage, and less cost to the institution. METHODS: From 2008 to 2011, a total of 16 traumatic aortic disruptions were evaluated and managed with endovascular techniques. The last six were treated with abdominal aortic extensions cuffs (Excluder Extension Cuffs; W.L. Gore & Associates, Flagstaff, AZ) rather than traditional thoracic stent grafts. In addition to demographics and trauma-related data, additional endpoints evaluated in this retrospective review included operative time, number of cuffs used, stent cost data, procedural complications, and follow-up. RESULTS: All six patients (five men/one woman) with traumatic aortic disruption were successfully treated with complete exclusion of the disruption using abdominal aortic cuffs. There were no complications including death or spinal cord ischemia. The average age was 27 years (range, 18-44 years). The average number of cuffs used to cover the traumatic tear was 2.6 per patient (range, 2-3 cuffs per patient), covering an average of 5.3 cm of thoracic aorta (range, 4-6 cm). Mean procedure time was 70 minutes. Hospital cost for each cuff was $2200 (average total stent cost per patient, $5720). For comparison, a single 10-cm conformable thoracic aortic graft (CTAG) (Gore) costs $14,500. Average follow-up of all six patients for up to 3 years demonstrates no complications or migration of the stent grafts. CONCLUSIONS: Traumatic aortic disruptions can be safely and selectively managed with "stacked" abdominal aortic extension cuffs. This tailored therapy may provide advantages over traditional thoracic stents, including improved size match in a younger trauma patient, less aortic coverage, and reduced cost.

Transmyocardial laser revascularization: from randomized trials to clinical practice. A review of techniques, evidence-based outcomes, and future directions.

Cardiac surgeons are increasingly faced with a more complex patient who has developed a pattern of diffuse coronary artery disease that cannot be completely revascularized by CAGB alone. Considering the increased operative and long-term cardiac risks predicted by incomplete revascularization, and the documented operative and long-term benefits associated with sole therapy and adjunctive TMR in randomized patients with diffuse coronary artery disease, increased use of sole therapy and adjunctive TMR therapy is warranted.

Comparison of recovery after mitral valve repair and replacement.

OBJECTIVE: We sought to examine the comparative improvement in health status after primary mitral valve repair versus replacement in patients with mitral valve regurgitation in a longitudinal setting. METHODS: We prospectively followed 267 patients with mitral valve regurgitation who underwent primary mitral valve repair (n = 163) and replacement (n = 104) between January 2002 and January 2005. Health status was evaluated at baseline and 1, 3, and 12 months after surgery with the validated short-form 36 and analyzed using generalized estimating equations with adjustment for propensity scores. RESULTS: Compared with patients undergoing mitral valve replacement, patients requiring valve repair were younger and more likely to be male. The probability of postsurgical readmission because of cardiac events was low and similar between the two treatment groups. New York Heart Association functional class was significantly improved after both procedures, with better improvement achieved by mitral valve repair (P < .01). For both treatment groups, scores for most of the short-form 36 domains were depressed at 1 month; however, after 3- and 12-month lags, dramatic improvements were achieved in most of the domains. Adjusted changes in the physical component score were similar between the two arms at each follow-up. For the mental component score, patients who underwent repair showed significant improvements compared with patients who underwent replacement at both 3 months (difference: 4.84 points, P = .005) and 12 months (difference: 5.92 points, P < .001). CONCLUSIONS: Our study suggests that after mitral valve surgery, there is significant improvement in New York Heart Association functional class and health status, especially in patients undergoing mitral valve repair.

Effects of omega-3 fatty acids on heart rate in cardiac transplant recipients.

Omega-3 fatty acid (n-3 FA) consumption has been linked to reductions in the risk of death from coronary heart disease and, recently, to lower heart rates (HRs). The investigators previously observed a reduction of 5 beats/min in HR in patients with coronary heart disease given n-3 FAs (eicosapentaenoic acid and docosahexaenoic acid) for 4 months. Reductions in HR may be explained by enhanced vagal tone, influences on cardiac voltage-gated ion channels, or both. The hypothesis that n-3 FAs would affect HR independent of vagal input was investigated by studying the effects of n-3 FA supplementation on HR in patients with denervated hearts after orthotopic heart transplantation. Electrocardiographic data obtained in 2 prospective trials in which 18 heart transplant recipients received n-3 FA supplementation (1 to 3.4 g/day) for 4 to 6 months were collected. Patients were studied 4.4 +/- 2.6 years after transplantation. HR, QRS complex, and QTc duration were determined before and after treatment. Pretreatment HR was reduced from 88 +/- 14 to 83 +/- 13 beats/min after n-3 FA treatment (p = 0.016). QRS duration increased from 107 +/- 24 to 117 +/- 25 ms (p = 0.001). QTc duration remained unchanged from baseline (427 +/- 34 ms) to study end (424 +/- 39 ms). In conclusion, n-3 FA supplementation reduced HR and prolonged QRS duration in heart transplant recipients who were presumably devoid of vagal innervation. These findings suggest that n-3 FAs may modify electrophysiologic properties of the myocardium itself.

Effect of difficulty affording health care on health status after coronary revascularization.

BACKGROUND: An objective of the United States' Healthy People 2010 Initiative is to eliminate disparities based on socioeconomic status. We assessed the effect of difficulty affording health care on the health status (symptoms, function, and quality of life) of patients treated with percutaneous coronary intervention or CABG. METHODS AND RESULTS: A consecutive, single-center cohort of 480 patients undergoing coronary revascularization received the Seattle Angina Questionnaire at the time of their procedure and at subsequent monthly intervals for 6 months. At baseline, patients who reported somewhat of a burden to a severe burden in affording health care had significantly lower scores on the Seattle Angina Questionnaire (mean+/-SD) with respect to angina (55+/-29 versus 68+/-25, P<0.0001), physical limitation (55+/-26 versus 72+/-24, P<0.0001), and quality of life (46+/-22 versus 56+/-22, P<0.0001) than those who did not perceive healthcare costs to be burdensome. Although both groups of patients improved after revascularization, poorer health status persisted among those with difficulty affording health care after percutaneous coronary intervention (6-month mean+/-SE: angina 79+/-2.5 versus 88+/-1.9, P=0.002; physical function 61+/-2.7 versus 80+/-2.0, P<0.0001; quality of life 67+/-2.4 versus 82+/-1.8, P<0.0001) but not after CABG (angina 91+/-2.5 versus 93+/-1.6, P=0.47; physical function 75+/-3.4 versus 81+/-2.2, P=0.13; quality of life 84+/-3.1 versus 84+/-2.0, P=0.81). Similar differences remained after adjustment for demographic and clinical characteristics. CONCLUSIONS: Patients reporting difficulty affording health care have worse health status at the time of coronary revascularization. A persistent disparity exists after percutaneous but not surgical revascularization. Additional inquiry into the mechanism of this disparity is needed so that the goals of equitable health care, irrespective of treatment strategy, can be achieved.

Risk of restenosis and health status outcomes for patients undergoing percutaneous coronary intervention versus coronary artery bypass graft surgery.

BACKGROUND: Previous comparisons of percutaneous coronary interventions (PCIs) and coronary artery bypass graft (CABG) surgery have demonstrated similar survival but have also generally found better health status outcomes (symptoms, function, and quality of life) with CABG. The principal limitation of PCI has been the occurrence of restenosis. No previous studies comparing the health status outcomes of PCI and CABG have examined differences in these outcomes as a function of patients' preprocedural risk for restenosis. METHODS AND RESULTS: We examined the health status outcomes, using the Seattle Angina Questionnaire (SAQ), among 1459 consecutive patients (1027 treated with PCI and 432, with CABG), stratified by their risk for restenosis. In multivariable-adjusted, linear regression analyses, no differences in 1-year angina or quality of life were observed among the 37.4% of patients at low risk for restenosis. However, among the 46.7% at intermediate risk for restenosis, 1-year health status scores were moderately better after CABG surgery compared with PCI (difference in SAQ angina frequency scores favoring CABG=6.1+/-1.7 points, P=0.0003; difference in SAQ quality of life=5.8+/-1.6 points, P=0.0004). Even larger differences in 1-year outcomes favoring CABG surgery were observed in patients at high risk for restenosis (SAQ angina frequency difference=10.8+/-4.2, P=0.01; SAQ quality of life difference=10.8+/-3.9, P=0.006). CONCLUSIONS: The relative health status benefits of CABG surgery compared with PCI increase as the risk of restenosis increases. Although selecting CABG or PCI is complex, preprocedural restenosis risk should be considered. It should also be tested as a means for considering drug-eluting as opposed to bare metal stents in PCI.

Tricuspid annuloplasty significantly reduces early tricuspid regurgitation after biatrial heart transplantation.

BACKGROUND: The incidence of tricuspid annuloplasty (TR) observed early after cardiac biatrial implantation is unpredictable and in our experience not infrequently problematic. Although the bicaval method of implant may reduce the incidence of TR, its benefit has not been conclusively documented. METHODS: In an attempt to reduce the incidence of TR observed early after cardiac transplantation, 25 consecutive patients undergoing cardiac transplantation received donor heart tricuspid annuloplasty (TA) with either a DeVega or Ring technique. Early transthoracic echocardiograms were analyzed and compared with an immediately prior and consecutive cohort of 25 patients undergoing transplantation without TA. The biatrial technique of cardiac transplantation with a Cabrol modification was used for donor heart implant in both groups. Echocardiograms obtained 5 days after cardiac transplantation were reviewed in blinded fashion. TR was scored 0 = none, 1 = mild, 2 = moderate, and 3 = severe. RESULTS: Donor and recipient characteristics were not different between groups. No hospital deaths occurred in either group. Patients undergoing transplantation without TA had a higher TR score, 1.3 (range 0-3), than did patients with TA, 0.7 (range 0-1.5, p = 0.002). Moderate or severe TR was present in 8 of 25 patients without TA compared with 0 of 25 patients with TA (p = 0.004). No patients required permanent pacemaker. CONCLUSIONS: TA can significantly reduce the incidence of early postoperative TR after biatrial cardiac transplant without adding to the complexity of operation.