Victor Chu

Transcatheter aortic valve implantation for the treatment of severe symptomatic aortic stenosis in patients at very high or prohibitive surgical risk: acute and late outcomes of the multicenter Canadian experience.

OBJECTIVES The aim of this study was: 1) to evaluate the acute and late outcomes of a transcatheter aortic valve implantation (TAVI) program including both the transfemoral (TF) and transapical (TA) approaches; and 2) to determine the results of TAVI in patients deemed inoperable because of either porcelain aorta or frailty. BACKGROUND Very few data exist on the results of a comprehensive TAVI program including both TA and TF approaches for the treatment of severe aortic stenosis in patients at very high or prohibitive surgical risk. METHODS Consecutive patients who underwent TAVI with the Edwards valve (Edwards Lifesciences, Inc., Irvine, California) between January 2005 and June 2009 in 6 Canadian centers were included. RESULTS A total of 345 procedures (TF: 168, TA: 177) were performed in 339 patients. The predicted surgical mortality (Society of Thoracic Surgeons risk score) was 9.8 +/- 6.4%. The procedural success rate was 93.3%, and 30-day mortality was 10.4% (TF: 9.5%, TA: 11.3%). After a median follow-up of 8 months (25th to 75th interquartile range: 3 to 14 months) the mortality rate was 22.1%. The predictors of cumulative late mortality were peri-procedural sepsis (hazard ratio [HR]: 3.49, 95% confidence interval [CI]: 1.48 to 8.28) or need for hemodynamic support (HR: 2.58, 95% CI: 1.11 to 6), pulmonary hypertension (PH) (HR: 1.88, 95% CI: 1.17 to 3), chronic kidney disease (CKD) (HR: 2.30, 95% CI: 1.38 to 3.84), and chronic obstructive pulmonary disease (COPD) (HR: 1.75, 95% CI: 1.09 to 2.83). Patients with either porcelain aorta (18%) or frailty (25%) exhibited acute outcomes similar to the rest of the study population, and porcelain aorta patients tended to have a better survival rate at 1-year follow-up. CONCLUSIONS A TAVI program including both TF and TA approaches was associated with comparable mortality as predicted by surgical risk calculators for the treatment of patients at very high or prohibitive surgical risk, including porcelain aorta and frail patients. Baseline (PH, COPD, CKD) and peri-procedural (hemodynamic support, sepsis) factors but not the approach determined worse outcomes.

Long-Term Outcomes After Transcatheter Aortic Valve Implantation Insights on Prognostic Factors and Valve Durability From the Canadian Multicenter Experience

OBJECTIVES This study sought to evaluate the long-term outcomes after transcatheter aortic valve implantation (TAVI) in the Multicenter Canadian Experience study, with special focus on the causes and predictors of late mortality and valve durability. BACKGROUND Very few data exist on the long-term outcomes associated with TAVI. METHODS This was a multicenter study including 339 patients considered to be nonoperable or at very high surgical risk (mean age: 81 ± 8 years; Society of Thoracic Surgeons score: 9.8 ± 6.4%) who underwent TAVI with a balloon-expandable Edwards valve (transfemoral: 48%, transapical: 52%). Follow-up was available in 99% of the patients, and serial echocardiographic exams were evaluated in a central echocardiography core laboratory. RESULTS At a mean follow-up of 42 ± 15 months 188 patients (55.5%) had died. The causes of late death (152 patients) were noncardiac (59.2%), cardiac (23.0%), and unknown (17.8%). The predictors of late mortality were chronic obstructive pulmonary disease (hazard ratio [HR]: 2.18, 95% confidence interval [CI]: 1.53 to 3.11), chronic kidney disease (HR: 1.08 for each decrease of 10 ml/min in estimated glomerular filtration rate, 95% CI: 1.01 to 1.19), chronic atrial fibrillation (HR: 1.44, 95% CI: 1.02 to 2.03), and frailty (HR: 1.52, 95% CI: 1.07 to 2.17). A mild nonclinically significant decrease in valve area occurred at 2-year follow-up (p < 0.01), but no further reduction in valve area was observed up to 4-year follow-up. No changes in residual aortic regurgitation and no cases of structural valve failure were observed during the follow-up period. CONCLUSIONS Approximately one-half of the patients who underwent TAVI because of a high or prohibitive surgical risk profile had died at a mean follow-up of 3.5 years. Late mortality was due to noncardiac comorbidities in more than one-half of patients. No clinically significant deterioration in valve function was observed throughout the follow-up period.

Isoprostanes constrict human radial artery by stimulation of thromboxane receptors, Ca2+ release, and RhoA activation

OBJECTIVES Radial artery vasospasm remains a potential cause of early graft failure after coronary bypass graft surgery, despite pretreatment with alpha-adrenergic or calcium channel blockers. We examined the roles of isoprostanes and prostanoid receptors selective for thromboxane A2 in the vasoconstriction of human radial arteries. METHODS Human radial arterial segments were pretreated intraoperatively with verapamil/papaverine or nitroglycerine/phenoxybenzamine, or not treated. In the laboratory, we measured isometric contractions in ring segments, vasoconstriction in pressurized segments, and changes in [Ca2+] and K+ currents in single cells. RESULTS Although phenoxybenzamine eliminated adrenergic responses, the isoprostane 15-F(2t)-IsoP and 2 closely related E-ring molecules (15-E(1t)-IsoP and 15-E(2t)-IsoP) still evoked powerful contractions; 15-E(2t)-IsoP was approximately 10-fold more potent than the other 2 agents. Responses were mediated through thromboxane receptors because they were sensitive to ICI-192605. Furthermore, they were sensitive to the Rho-kinase inhibitors Y-27632 or H-1152 (both 10(-5) mol/L) or to cyclopiazonic acid (which depletes the internal Ca2+ pool), but not to nifedipine. In single cells, 15-E(2t)-IsoP elevated [Ca2+]i and suppressed K+ current. CONCLUSIONS Isoprostanes accumulate after coronary artery bypass graft surgery, yet none of the currently available antispasm treatments for radial artery grafts is effective against isoprostane-induced vasoconstriction. It is imperative that more specific treatment strategies be developed. We found that isoprostane responses in radial arteries are mediated by prostanoid receptors selective for thromboxane A2 with activation of Rho-kinase and release of Ca2+. Pretreatment of radial artery grafts with Rho-associated kinase inhibitors may potentially reduce postoperative graft spasm. Clinical studies to test this are indicated.

Treatment assignment of high-risk symptomatic severe aortic stenosis patients referred for transcatheter AorticValve implantation.

Transcatheter aortic valve implantation (TAVI) has become an option for patients with symptomatic severe aortic stenosis whose co-morbidities place them at high surgical risk. However, little is known regarding treatment allocation. From May 2008 to May 2011, all high-risk patients with symptomatic severe aortic stenosis referred to an experienced single-center TAVI clinic were reviewed. A total of 170 consecutive patients were evaluated. Of these, 58 (34%) were accepted for TAVI (mean age 81 ± 8 years). Thirty-three patients (19%) were accepted for conventional aortic valve replacement (AVR; mean age 83 ± 6 years). Sixty-two patients (37%) were treated conservatively (mean age 83 ± 6 years). Seventeen patients (10%) died awaiting complete assessment. At 30 days, all-cause mortality was 10% in the TAVI group, 3% in the conventional AVR group, and 32% in the conservatively treated group. Multivariate-adjustment identified the absence of chronic obstructive pulmonary disease (hazard ratio 0.30, 95% confidence interval 0.09 to 0.98, p <0.05) and the absence of frailty (hazard ratio 0.19, 95% confidence interval 0.07 to 0.55, p <0.01) as independent predictors of conventional AVR. In conclusion, of the high-risk patients with severe aortic stenosis referred for TAVI at a large single center, approximately 1/2 were accepted for intervention (conventional AVR or TAVI), and roughly 1/3 were treated conservatively.

Reduction of arterial graft smooth muscle mass by moderate heat therapy

Radial artery (RA) graft spasm is a major cause of early graft failure in coronary artery bypass grafting surgeries. We explored the feasibility of thermal reduction of smooth muscle mass to attenuate vasoconstriction. Rat and rabbit femoral arteries were treated thermally in situ (45°C to 65°C; 0 s to 120 s) and then excised at various time points for histological and physiological study (pressure-diameter relationships). Human radial arteries were treated in vitro and studied in similar fashion. Weeks after thermal treatment, no overt indication was noted of vasospasm, thrombosis, or scarring in the arterial wall; however, this intervention led to a thermal dose-dependent reduction of vasoconstriction (to phenylephrine or potassium chloride) and to a conspicuous loss of smooth muscle. Pressure-diameter relationships showed no aneurismal dilation of these demuscularized arteries up to 200 mmHg. Qualitatively identical results were obtained in human radial arteries. Thermal ablation of RAs may provide a simple, safe, and effective solution to postsurgical vasospasm.

Structural and electrophysiological changes in atherosclerotic radial artery grafts account for impairment of vessel reactivity

To evaluate the potential impact of using atherosclerotic radial artery (RA) conduits as grafts in coronary artery bypass surgery, we examined the vasoconstrictor and electrophysiological properties of mildly and severely atherosclerotic RAs. Vasoconstrictor responses were measured in cannulated and pressurized (85mmHg) RA segments and K(+) currents were measured in single smooth muscle cells. In the cannulated and pressurized vessel preparation, the pressure-induced dilation was attenuated in both the mildly and severely atherosclerotic RAs when compared to normal samples. Contractile responses to potassium chloride, thromboxane A(2) (TXA(2)) analog U-46619 and to E-ring and F-ring isoprostanes were also attenuated. Smooth muscle cells (SMCs) from atherosclerotic arteries manifested significantly greater K(+) current density (76.6+/-22.4pA/pF) when compared to normal SMCs (18.6+/-3.3pA/pF). Our results show that vasocontractile properties of both mildly and severely atherosclerotic arteries are reduced when compared to normal RAs. A possible explanation for this could be decreased vascular compliance due to arterial stiffening and a substantial augmentation of K(+) currents in sclerotic smooth muscle cells. We conclude that caution should be exercised when using RA grafts with atherosclerotic lesions since they could significantly impact the clinical outcome of CABG surgery.

Double Trouble: A Case of Valvular Disease in Pregnancy.

Patient presentation: A 29-year-old woman born in Canada, gravida 3, para 2 at 12 weeks gestation, presented to the cardiac pregnancy clinic with a 1-month history of progressive shortness of breath on exertion and chest discomfort. Her medical history was significant for stenosis of a congenital bicuspid aortic valve for which she underwent surgical aortic valve replacement with a #23 Carpentier-Edwards Perimount Magna ease porcine bioprosthetic valve 5 years earlier at the age of 24. There was a questionable history of rheumatic fever at the age of 21; investigations revealed positive antistreptolysin and Sjögren-specific antibody A titers. She was treated with valproic acid for an irregular tremor thought to be Syndenham chorea. The pathology from her surgery did not reveal any evidence of rheumatic disease. She went on to have 2 successful pregnancies at the age of 26 and 27 years without complications. Her last formal review was 1 year before, during her second pregnancy at 34 weeks gestation. Echocardiography showed mild prosthetic valve aortic stenosis with a peak/mean gradient of 41/27 mm Hg, normal ejection fraction, with increased gradients across the prosthetic valve thought to be secondary to a high-output state. She became pregnant unexpectedly 9 months after her second pregnancy and now had progressive shortness of breath and typical angina on exertion; she was unable to climb 1 flight of stairs or push her baby’s stroller without having to stop for prolonged periods. Her medications included aspirin, monthly intramuscular penicillin, and maternal vitamins. On physical examination, her blood pressure was 105/66 mm Hg, heart rate 101 beats/min regular, and normal respiratory rate; oxygen saturation was 98% on room air. She was comfortable and in no acute distress. Jugular venous pressure was 5 cm above the sternal angle with a negative abdominojugular reflex. Carotid pulse was of normal volume and contour, with no audible bruits. There was a midline sternotomy scar and the apical impulse was sustained. Auscultation revealed a normal S1, grade 2 late-peaking systolic ejection murmur best heard at the base with radiation to the carotid base, soft S2, and no S3 or S4. Lungs were clear to auscultation bilaterally. There was no pedal edema, all peripheral pulses were palpable, and the abdomen was soft, nontender. A 12-lead ECG revealed sinus tachycardia, with normal axis, normal intervals, and borderline left ventricular hypertrophy by voltage criteria (Figure 1).

MitraClip and Transcatheter Aortic Valve Replacement in a Patient With Recurrent Heart Failure

An 85-year-old man presented to the emergency department with a 3-week history of progressive dyspnea, orthopnea, and mild ankle edema without chest discomfort. His past medical history was significant for coronary artery disease with a non–ST-segment–elevation myocardial infarction 8 years prior with percutaneous coronary intervention to the distal right coronary artery, with mild residual nonobstructive disease in the left anterior descending artery and circumflex artery. Cardiovascular risk factors included hypertension, dyslipidemia, and chronic kidney disease stage 3. His remaining medical history was significant for cecal adenocarcinoma with a right hemicolectomy 20 years prior, and pulmonary sarcoidoisis that was quiescent without any history of steroid use or immunosuppression. The most recent pulmonary function tests revealed normal spirometry and diffusion capacity. He was a nonsmoker, and before the onset of symptoms he was functionally independent only using a cane for mobility. Initial vital signs revealed a regular heart rate of 81 bpm, and blood pressure of 121/78 mm Hg. He was afebrile, and his oxygen saturation was 95% on 2-L nasal prongs. Jugular venous pressure was elevated at 7 cm above the sternal angle with a normal waveform; the hepatojugular reflex was positive. The carotid pulse was of decreased volume but normal contour, without audible bruits. Auscultation revealed a normal S1 and S2, a holosystolic murmur at the apex, and a grade 2 midpeaking systolic ejection murmur at the base, with radiation to the carotids. Respiratory examination revealed clear and equal breath sounds bilaterally with the presence of bibasilar crackles at the lung bases. Peripheral pulses were present, with bilateral pitting edema at the ankles. Abdominal examination was unremarkable. Initial investigations revealed hemoglobin of 103 g/dL, and electrolytes within the normal range with a creatinine of 121 mmol/L (estimated glomerular filtration rate 50 mL/min). Troponin I (high sensitivity) was elevated with peak of …