Schaff, Hartzell V.

Objectives We investigated haemodynamics and clinical outcomes according to type of pulmonary hypertension (PH) in patients with constrictive pericarditis (CP). Background As the prevalence of CP with concomitant myocardial disease (mixed CP) grows, PH is more commonly seen in patients with CP. However, haemodynamic and outcome data according to the presence or absence of PH are limited. Methods 150 patients with surgically confirmed CP who underwent echocardiography and cardiac catheterisation within 7 days at two tertiary centres were divided into three groups: no-PH, isolated postcapillary PH (Ipc-PH) and combined postcapillary and precapillary PH (Cpc-PH). Primary outcome was all-cause mortality during follow-up. Result In this retrospective cohort study, 110 (73.3%) had PH (mean pulmonary artery pressure ≥25 mm Hg). Cpc-PH, using defined cut-offs for pulmonary vascular resistance (>3 Wood units) or diastolic pulmonary gradient (≥7 mm Hg), was seen in 18 patients (12%). The Cpc-PH group had a higher prevalence of comorbidities (diabetes and atrial fibrillation) and concomitant myocardial disease as an aetiology of CP than other groups. Pulmonary vascular resistance had a significant direct correlation with medial E/e′ by Doppler echocardiography (r=0.404, p<0.001). Survival rate was significantly lower in the Cpc-PH than the no-PH (p=0.002) and Ipc-PH (p=0.024) groups. On multivariable analysis, age, New York Heart Association functional class IV, medial e′ velocity, Cpc-PH and Ipc-PH were independently associated with long-term mortality. Conclusion Combined postcapillary and precapillary PH develops in a subset of patients with CP and is associated with long-term mortality after pericardiectomy.

Introduction: Pulmonary valve (PV) replacement is rare, so data regarding normal hemodynamics are limited. We sought to determine the normal Doppler-derived hemodynamic profiles of various PV prostheses (PVPs) in adults. Hypothesis: Doppler-derived hemodynamic profiles of normal PVPs will vary according to prosthesis type in adult patients. Methods: We performed a retrospective review of comprehensive two dimensional and Doppler echocardiographic examinations of 327 patients (median age, 35; range 18 -83 years) with normal PVPs performed early after implantation. Data were analyzed to determine mean±SD. Results: Parasternal short axis was the most commonly used window (96%) for assessment of PVPs. For the 327 PVPs, peak instantaneous gradient was 25±11 mmHg, mean systolic gradient was 13.1±6.1 mmHg, and mean right ventricular outflow tract velocity was 0.8±0.6 m/s. Results for selected variables analyzed by prosthesis type are listed in the Table. Pericardial prostheses had significantly lower peak gradient (21±10.1 mmHg; P=0.002) compared with porcine (25±9.7 mmHg), mechanical (26±16.6 mmHg), bovine venous (34±15.5 mmHg) and homograft PVPs (35±8.4 mm Hg). Conclusions: This is the largest series reporting normal Doppler-derived hemodynamic profiles of PVPs. This study establishes normative values for Doppler-derived variables for normal PVPs implanted in adults. Pericardial prostheses had the optimal hemodynamic profile in this patient population.

Background Carcinoid involvement of left-sided heart valves has been reported in patients with a patent foramen ovale, carcinoid tumor of the lung, and active carcinoid syndrome with high levels of serotonin. The present study details the clinical features and surgical management of patients with carcinoid heart disease affecting both left- and right-sided valves. Methods and Results Eleven patients (7 men, 4 women) with symptomatic carcinoid heart disease underwent surgery for left- and right-sided valve disease between 1989 and 1999. Mean age was 57±9 years, and median preoperative NYHA class was 3. All patients had metastatic carcinoid tumors and were on somatostatin analog. Of 11 patients, 5 (45%) had a patent foramen ovale; 1 of these also had a primary lung carcinoid tumor. Surgery included tricuspid valve replacement in all patients, pulmonary valve replacement in 3 and valvectomy in 7, mitral valve replacement in 6 and repair in 1, aortic valve replacement in 4 and repair in 2, CABG in 2, and patent foramen ovale closure in 5. One myocardial metastatic carcinoid tumor was removed. There were 2 perioperative deaths. At a mean follow-up of 41 months, 4 additional patients were dead. All but 1 surgical survivor initially improved ≥1 functional class. No patient required reoperation. Conclusions Carcinoid heart disease may affect left- and right-sided valves and occurred without intracardiac shunting in 55% of this surgical series. Despite metastatic disease that limits longevity, operative survivors had improvement in functional capacity. Cardiac surgery should be considered for select patients with carcinoid heart disease affecting left- and right-sided valves.

Background Mitral regurgitation (MR) due to mitral valve prolapse (MVP) is often treatable by surgical repair. However, the very long-term (>10-year) durability of repair in both anterior leaflet prolapse (AL-MVP) and posterior leaflet prolapse (PL-MVP) is unknown. Methods and Results In 917 patients (aged 65±13 years, 68% male), surgical correction of severe isolated MR due to MVP (679 repairs and 238 replacements [MVRs]) was performed between 1980 and 1995. Survival after repair was better than survival after MVR for both PL-MVP (at 15 years, 41±5% versus 31±6%, respectively; P =0.0003) and AL-MVP (at 14 years, 42±8% versus 31±5%, respectively; P =0.003). In multivariate analysis adjusting for predictors of survival, repair was independently associated with lower mortality in PL-MVP (adjusted risk ratio [RR] 0.61, 95% CI 0.44 to 0.85; P =0.0034) and in AL-MVP (adjusted RR 0.67, 95% CI 0.47 to 0.96; P =0.028). The reoperation rate was not different after repair or MVR overall (at 19 years, 20±5% for repair versus 23±5% for MVR; P =0.4) or separately in PL-MVP ( P =0.3) or AL-MVP ( P =0.3). However, the reoperation rate was higher after repair of AL-MVP than after repair of PL-MVP (at 15 years, 28±7% versus 11±3%, respectively; P =0.0006). From the 1980s to the 1990s, the RR of reoperation after repair of AL-MVP versus PL-MVP did not change (RR 2.5 versus 2.7, respectively; P =0.58), but the absolute rate of reoperation decreased similarly in PL-MVP and AL-MVP (at 10 years, from 10±3% to 5±2% and from 24±6% to 10±2%, respectively; P =0.04). Conclusions In severe MR due to MVP, mitral valve repair compared with MVR provides improved very long-term survival after surgery for both AL-MVP and PL-MVP. Reoperation is similarly required after repair or replacement but is more frequent after repair of AL-MVP. Recent improvement in long-term durability of repair suggests that it should be the preferred mode of surgical correction of MVP whether it affects anterior or posterior leaflets and is an additional incentive for early surgery of severe MR due to MVP.

Background —Patients who have had previous CABG may subsequently develop significant mitral valve (MV) dysfunction that requires surgical intervention. Methods and Results —We reviewed 80 consecutive patients who had had previous CABG and who underwent MV surgery between January 1972 and March 1997. Forty-seven (59%) had initial CABG elsewhere, and 5 had had previous CABG twice. The mean interval between the previous CABG and the MV surgery was 6.3 years (range, 4.4 months to −17 years). At least 15 patients had grade 1/4 to 2/4 mitral regurgitation at initial CABG. The study group included 59 men and 21 women, with a mean study group age of 65.5 years. Ninety-four percent had symptoms of congestive heart failure, 60% had angina, 96% were in NYHA class III to IV, and 37% had an ejection fraction (EF) <50%. Origin of the MV disease was ischemic in 33 patients, myxomatous in 19, combined ischemic and myxomatous in 16, rheumatic in 5, infective in 3, and unknown in 4. MV repair was performed in 46 patients (58%) and MV replacement (MVR) in 34. Concomitant repeat CABG was performed in 38 (48%) patients. In-hospital mortality was 7 of 80 (8.8%); no early death occurred among patients with myxomatous disease. EF <50% was the only significant predictor of early mortality. Overall 1-, 5-, and 10-year survival was 83.8%, 55.6%, and 34.4% respectively. Predictors of late cardiac death were preoperative NYHA class IV ( P =0.0006), urgent or emergency operation ( P <0.0001), use of intra-aortic balloon pump ( P =0.002), and EF <50% ( P =0.01). Seven patients had an additional reoperation: 4 received CABG, 2 MVR, and 2 MV repair. Conclusions —Ischemic, myxomatous, rheumatic, or infective MV dysfunction may develop subsequently after CABG. MVR or MV repair after previous CABG is associated with an acceptably low operative risk and good relief of symptoms. Left ventricular function is strongly correlated with both hospital and late mortality. Surgery should be done before LV dysfunction develops.

Background —Proliferation of the intima is an early lesion of saphenous vein graft disease. Early patency rates of radial artery grafts are acceptable, but little is known about their risk of intimal hyperplasia. Methods and Results —To develop a model of intimal hyperplasia, we incubated human saphenous veins, internal mammary arteries, and radial arteries (n=6, 8, and 10, respectively) in an organ culture with Rosewell Park Memorial Institute 1640 (30% serum) for 0, 4, 7, 10, and 14 days. Quantitative histological studies were performed, and the average intimal-to-medial (I/M) ratio was calculated for each incubation interval. After 10 and 14 days of culture, the I/M ratio increased in the saphenous veins ( P =0.03, P =0.04 versus 0 day, respectively). No significant increase occurred in the I/M ratio in either the internal mammary or radial arteries. Next, the ability of adenoviral gene transfers to inhibit intimal hyperplasia in the saphenous veins was evaluated. Adenoviral-mediated gene transfer of nitric oxide synthase significantly reduced the I/M ratio at 14 days compared with vehicle ( P =0.001) and virus ( P =0.004) controls. Conclusions —The human saphenous vein has a greater propensity for intimal hyperplasia than arterial grafts; the human radial artery behaves similarly to the internal mammary artery. In the future, gene therapy may augment nitric oxide synthase, limiting vein graft disease.

Background —Coronary arteries respond to hypoxia with transient relaxations, which increases coronary blood flow, in part, by release of nitric oxide. We hypothesized that increased expression of nitric oxide synthase might further augment blood vessel relaxation during hypoxia. The present study examined the effect of adenovirus-mediated transfer of bovine endothelial nitric oxide synthase (eNOS) on hypoxia-induced transient relaxations in canine coronary arteries. Methods and Results —Paired segments of coronary arteries were exposed to vehicle (phosphate-buffered saline with albumin) or an adenovirus encoding either E coli β-galactosidase (Ad.CMVLacZ, viral control; 10 10 pfu/mL) or eNOS (Ad.CMVeNOS; 10 10 pfu/mL) for 2 hours at 37°C. Immunohistochemistry with a monoclonal antibody specific for eNOS documented both endothelial and adventitial expression in Ad.CMVeNOS arteries, whereas vehicle and viral controls demonstrated only constitutive expression. Levels of cGMP were increased 5-fold in Ad.CMVeNOS arteries compared with controls. In arteries exposed to Ad.CMVeNOS, maximum contraction to prostaglandin F 2α was reduced compared with viral controls, and this effect was eliminated by pretreatment with a competitive inhibitor of eNOS ( N G -monomethyl- l -arginine, 10 −3 mol/L). Hypoxia-induced transient relaxation (95% N 2 -5% CO 2 ) in Ad.CMVeNOS arteries (45.2±8.8%, n=6) was augmented compared with vehicle (26.3±6.0%) or viral (27.2±7.1%) controls. Conclusions —Adenovirus-mediated gene transfer of nitric oxide synthase reduces receptor-dependent contractions and augments hypoxia-induced relaxations in canine coronary arteries; this method of augmentation of NO production might be advantageous for reduction of coronary artery vasospasm.

Background. Apical hypertrophic cardiomyopathy (AHCM) has been considered a ``benign” form of HCM in Asian and non-Asian patients (pt). However, data on long-term outcome of pt with AHCM are limited. The purpose of this study was to determine the natural history of pt with AHCM followed at a tertiary referral center in North America. Methods. Between July 1976 and September 2006, 193 pt with the diagnosis of AHCM were seen at the Hypertrophic Cardiomyopathy Clinic. The last echocardiographic exam was reviewed in all pt. Follow-up data were obtained where possible (clinic visit). Results. Mean age at diagnosis 56±17 years, mean age at first presentation at our center was 58±17 years. Symptoms included chest pain in 69 pt (36 %), and exertional dyspnea ≥NYHA II in 97 pt (50 %). A family history of either HCM and/or sudden cardiac death was reported by 36 pt (19 %). Coronary artery disease was proven in 40 pt (21 %). Median follow up was 50 months (1–318) and obtained in 124 pt (64 %). The following events were reported at the last clinic visit: heart failure in =5 pt, syncope in =0 pt, ventricular tachycardia in =7 pt, ICD implantation in 22 pt, and stroke in 22 pt. Death from all causes occurred in 51 of 193 pt (26 %) at a mean age of 72 years (14–78). Kaplan-Meier survival analysis was used to examine survival from all causes of death since first presentation. Observed survival in patients with AHCM was significantly less than expected in an age- and gender matched Minnesota white population (p=0.009). The observed survival at 5, 10 and 15 years was 87 %, 82 %, and 57 % respectively, while the expected survival for these time points was 91 %, 81 %, and 72 %. Conclusions. AHCM in this predominantly North American patient population is associated with an increased mortality. Patients with AHCM have a high incidence of significant cardiovascular symptoms and ventricular arrhythmias. As the disease is less benign than previously suspected, careful longitudinal care by a cardiologist is warranted.

Introduction: In asymptomatic patients with severe aortic stenosis (SAS), left ventricular (LV) ejection fraction (EF) <50% is generally considered to be the threshold for referral for aortic valve replacement (AVR). Hypothesis: We investigated the importance of LVEF on long-term outcome after AVR in symptomatic and asymptomatic SAS patients and studied whether LVEF < 50% is the optimal threshold for referral for AVR. Methods and Results: We retrospectively identified 2017 patients with SAS (aortic valve area (AVA)<1cm2, mean aortic valve gradient ≥40 mm Hg, or indexed AVA <0.6 cm2/m2) who underwent surgical AVR from January 1995 to June 2009 at our institution. Patients were divided into 4 groups depending on preoperative LVEF (<50% in 300 (15%) patients, 50-59% in 331 (17%), 60-69% in 908 (45%), and ≥70% in 478 (24%)). The primary end-point was all-cause mortality. During follow-up of 5.3±4.4 years, 1056 (52%) died. Five-year mortality rate increased with decreasing LVEF (41% (n=106), LVEF<50%); 35% (n=98), LVEF 50-59%; 26% (n=192), LVEF 60-69%; 22% (n=90), LVEF≥70%, p<0.0001). Compared to patients with LVEF≥60%, patients with LVEF 50-59% had increased mortality (HR 1.58, p<0.001), with a similar risk increase in both symptomatic (HR=1.56, p<0.001) and asymptomatic patients (HR 1.58, p=0.006, Figure). In a Cox regression analysis corrected for standard risk factors, LV mass index, AVA, and stroke volume index, LVEF was predictive of all-cause mortality (HR=0.89 per 10%, p<0.001). When this multivariable analysis was repeated in the subset of 1333 patients with no history of coronary artery disease, LVEF was still associated with all-cause mortality (HR=0.90 per 10%, p=0.009). Conclusion: In patients with SAS undergoing AVR, patients with LVEF 50-59% have also increased mortality compared to patients with LVEF>60%, suggesting that a different LVEF threshold should be used when referring for AVR.