Ex vivo heart perfusion after cardiocirculatory death; a porcine model.

BACKGROUND: Donation after cardiocirculatory death (DCD) has lead to an increase in organ availability. However, because of medical, logistic, and ethical issues, the use of hearts from DCD donors for transplantation is not generally considered to be feasible. In this study, we investigated the feasibility of ex vivo resuscitation and assessment of the porcine heart after circulatory death using the organ care system (OCS). METHODS: Cardiocirculatory death was induced in five pigs by cessation of mechanical ventilation. No heparin was administered. The agonal time (AT) was calculated as the time between a reduction of blood pressure <50 mm Hg or a fall in saturation beneath 70% and the cessation of electrical activity. After a further 15 min of warm ischemia, hearts were procured and implanted into the OCS, mimicking the actual clinical scenario for other organs. Thus, procured grafts were assessed ex vivo over a period of 4 h. RESULTS: Four hearts were successfully resuscitated on the system (AT 8, 15, 20, and 34 min) Three grafts had excellent visual contractility and lactate trends and were considered to be transplantable. One graft (AT 34 min) had an increased lactate and abnormal contractility being unsuitable for transplantation. One heart with 48-min AT could not be resuscitated. CONCLUSIONS: Our data show that hearts from nonheparinized DCD porcine donors can be successfully resuscitated using the OCS in a scenario, which closely simulates clinical conditions.

Regional right ventricular strain pattern in patients with acute pulmonary embolism.

AIMS: Right ventricular (RV) dysfunction is a frequent consequence of pulmonary embolism (PE) and a marker of increased risk. However, current qualitative methods assessing RV function are imprecise. We sought to determine whether RV strain analysis would have clinical utility in patients with PE compared with normal controls. METHODS AND RESULTS: We compared 75 acute PE subjects (mean age 54 ± 16) with 30 normal controls (mean age 50 ± 15). Regional RV longitudinal strain was assessed using offline speckle tracking software to obtain strain and strain rate data from the basal, mid, and apical free wall and septum. Global RV free wall and septal strain was significantly reduced in PE subjects (-14.17 (±5.96) vs -24.92 (±4.16), P < 0.0001; -14.99 (±5.55) vs -18.54 (±7.34), P = 0.0082). Regional RV strain was markedly reduced in PE subjects in all regions of the free wall and in the mid and basal septum (P < 0.05). Strain rates of PE subjects were significantly reduced in all segments of the RV free wall (P < 0.05). In 36 PE subjects with regional RV dysfunction ("McConnell sign"), strain in the apical free wall was significantly reduced in comparison to those without (-10.08 vs -13.51; P = 0.0420), in parallel with higher RV:LV ratios (1.30, ±1.01 vs 0.78, ±0.16; P = 0.0035) and lower RV fractional area change (32.06, ±14.42 vs 42.52, ±11.61; P = 0.0021). CONCLUSIONS: Regional RV longitudinal strain is altered in the free wall and mid and basal septum in subjects with acute PE. Strain rates are only reduced in the RV free wall.

Mechanical dyssynchrony after myocardial infarction in patients with left ventricular dysfunction, heart failure, or both.

BACKGROUND: Mechanical dyssynchrony is considered an independent predictor for adverse cardiovascular outcomes in patients with heart failure. However, its importance as a risk factor after myocardial infarction is not well defined. METHODS AND RESULTS: We examined the influence of mechanical dyssynchrony on outcome in patients with left ventricular dysfunction, heart failure, or both after myocardial infarction who were enrolled in the Valsartan in Acute Myocardial Infarction (VALIANT) echocardiography study. B-mode speckle tracking with velocity vector imaging was used to assess ventricular synchrony in 381 patients who had image quality sufficient for analysis. Time to regional peak velocity and time to strain rate were measured among 12 left ventricular segments from the apical 4- and 2- chamber views, and the SDs between all 12 segments were used as a measure of dyssynchrony. The relationships between the SD of time to regional peak velocity and strain rate and clinical outcome of death or heart failure were assessed. In a multivariate Cox model adjusted for clinical and echocardiographic variables, the SD of time to peak velocity (hazard ratio per 10 ms, 1.10; 95% confidence interval, 1.02 to 1.18; P=0.010) and the SD of time to strain rate (hazard ratio per 10 ms, 1.16; 95% confidence interval, 1.06 to 1.27; P=0.001) were independent predictors of death or heart failure. CONCLUSIONS: Left ventricular dyssynchrony is independently associated with increased risk of death or heart failure after myocardial infarction, suggesting that contractile pattern may play a role in post-myocardial infarction prognosis.

Effect of intensive versus standard blood pressure lowering on diastolic function in patients with uncontrolled hypertension and diastolic dysfunction.

Diastolic dysfunction may precede development of heart failure in hypertensive patients. We randomized 228 patients with uncontrolled hypertension, preserved ejection fraction, and diastolic dysfunction to 2 targeted treatment strategies: intensive, with a systolic blood pressure target of <130 mm Hg, or standard, with a systolic blood pressure target of <140 mm Hg, using a combination of valsartan, either 160 or 320 mg, plus amlodipine, either 5 or 10 mg, with other antihypertensive medications as needed. Echocardiographic assessment of diastolic function was performed at baseline and after 24 weeks in a prospective, open-label, blinded end point design. Blood pressure was reduced significantly in both groups, from 161.2+/-13.9/90.1+/-12.0 to 130.8+/-12.3/74.9+/-9.1 mm Hg (P<0.0001) in the intensive arm and from 162.1+/-13.2/93.7+/-12.2 to 137.0+/-12.9/79.6+/-11.0 mm Hg (P<0.0001) in the standard arm (P<0.003 for between-group comparisons). Myocardial relaxation velocity improved from 7.6+/-1.1 to 9.2+/-1.7 cm/s (Delta 1.54+/-1.4 cm/s; P<0.0001) in the intensive arm and from 7.5+/-1.3 to 9.0+/-1.9 cm/s (Delta 1.48+/-1.6 cm/s; P<0.0001) in the standard arm, with no difference between the 2 strategies in the achieved improvement (P=0.58). The degree of improvement in annular relaxation velocity was associated with the extent of systolic blood pressure reduction, and patients with the lowest achieved systolic blood pressure had the highest final diastolic relaxation velocities.

Longitudinal and circumferential strain rate, left ventricular remodeling, and prognosis after myocardial infarction.

OBJECTIVES: We sought to investigate the clinical prognostic value of longitudinal and circumferential strain (S) and strain rate (SR) in patients after high-risk myocardial infarction (MI). BACKGROUND: Left ventricular (LV) contractile performance after MI is an important predictor of long-term outcome. Tissue deformation imaging might more closely reflect myocardial contractility than traditional measures of systolic functions. METHODS: The VALIANT (Valsartan in Acute Myocardial Infarction Trial) Echo study enrolled 603 patients with LV dysfunction, heart failure, or both 5 days after MI. We measured global peak longitudinal S and systolic SR (SRs) from apical 4- and 2-chamber views and global circumferential S and SRs from parasternal short-axis view with speckle tracking software (Velocity Vector Imaging, Siemens, Inc., Mountain View, California). We related global S and SRs to LV remodeling at 20-month follow-up and to clinical outcomes. RESULTS: Both longitudinal (mean: -5.1 ± 1.6 100/ms) and circumferential SRs (mean: -8.0 ± 2.8 100/ms) were predictive of death or hospital stay for heart failure (hazard ratio: 2.4, 95% confidence interval [CI]: 2.0 to 3.1, p < 0.001; hazard ratio: 1.3, 95% CI: 1.2 to 1.4, p < 0.001, respectively) after adjustment for clinical covariates by Cox proportional hazards, and longitudinal SRs further improved in predicting 18-month survivor on a model based on clinical and standard echocardiographic measures (increase in area under the receiver-operator characteristic curve: 0.13, p = 0.009). With multivariable logistic regression, circumferential SRs, but not longitudinal SRs, was strongly predictive of remodeling (odds ratio: 1.3, 95% CI: 1.1 to 1.4, p < 0.001). CONCLUSIONS: Both longitudinal and circumferential SRs were independent predictors of outcomes after MI, whereas only circumferential SRs was predictive of remodeling, suggesting that preserved circumferential function might serve to restrain ventricular enlargement after MI.

EXCEED: Exforge-intensive control of hypertension to evaluate efficacy in diastolic dysfunction: study rationale, design, and participant characteristics.

BACKGROUND: Both diastolic dysfunction and increased vascular stiffness represent important measures of target-organ damage in hypertension. Whether intensive blood pressure (BP) control can further improve these measures remains unknown. METHODS: EXCEED is a prospective, randomized open-label blinded endpoint trial (PROBE) design, aiming to test the hypothesis that more aggressive BP lowering would result in greater improvement in diastolic function among patients with stage II hypertension, evidence of diastolic dysfunction and preserved systolic function (EF > or = 50%). Patients were randomized to one of two treatment strategies, targeting systolic blood pressure (SBP) <140 mmHg or <130 mmHg using a combination of amlodipine/valsartan with additional antihypertensive medications as needed to achieve the prescribed targets. Diastolic function was assessed using Doppler tissue imaging of early diastolic velocity of lateral mitral annulus (E'), while vascular stiffness was assessed using radial augmentation index (RAI) derived from radial artery tonometry. The study primary endpoint will be the change in lateral E' velocity between baseline and 24 weeks. RESULTS: Two hundred and twenty eight patients (50% female) with mean age of (59.6+/-9.7) years and mean BP of (162+/-14/92+/-13 mmHg) were randomized equally to either treatment strategies. Left ventricular hypertrophy was present among <4% of the enrolled patients. Inspite diastolic function was impaired, baseline lateral E' velocity (7.6+/-1.2 cm/s) was not related to baseline SBP while baseline RAI was weakly related (r = 0.2, p <0.01) to SBP even after adjustment to age, gender and heart rate. CONCLUSION: EXCEED will determine whether intensive BP lowering will further improve diastolic dysfunction and vascular stiffness among patients with uncontrolled hypertension.