Fractional Area Of Contraction Research Articles

The effects of SGLT2 inhibitors on right ventricle functions in heart failure patients: update meta-analysis of the current literature

Abstract Background There is some discrepancy in the present studies concerning the effect of sodium-glucose cotransporter type 2 (SGLT2) inhibitors on right ventricular (RV) functions in heart failure (HF) patients. The current meta-analysis was focused on determining the impact of SGLT2 inhibitors on RV functions in such individuals. Methods Two independent investigators searched PubMed, Google Scholar, and the Cochrane Library for articles of interest. To analyze heterogeneity, Higgins' I2 as well as prediction intervals and Egger's test were utilized to assess heterogeneity. The Newcastle-Ottawa standard ratings approach was used to assess the quality of observational studies. The Robin-I risk of bias algorithm was used to assess the bias risks of randomized studies. Results This meta-analysis evaluated 8 studies in total. Over the follow-up time frame, patients who used SGLT-2 inhibitors had substantially lower systolic pulmonary artery pressure (sPAP) and higher TAPSE values (mean difference (MD) = 1.30 [0.78;1.82], p =0.002 and MD =-5.39 [-7.88; -2.89], p=0.003, respectively). There was no significant difference in RVS’ values between follow-up and baseline (MD=1.38 [-1.35;3.80], p=0.169). However, as compared to the baseline period, fractional area contraction (FAC) values were substantially larger at the end of the follow-up period (MD=5.40 [3.74;7.07], p=0.015). Conclusion To the best of our knowledge, this is the first meta-analysis assessing the impact of SGLT2 inhibitors on RV function in HF patients. Our findings suggest that SGLT2 inhibitors may improve RV performance in HF patients.

Effects of SGLT2 inhibitors on right ventricular function in heart failure patients: Updated meta-analysis of the current literature.

There is some discrepancy in current studies concerning the effect of sodium-glucose cotransporter type 2 inhibitors (SGLT2i) on right ventricular (RV) functions in heart failure (HF) patients. Hence, this meta-analysis was focused on determining the impact of SGLT2i on RV functions in such individuals. Two independent investigators searched PubMed, Google Scholar, and the Cochrane Library for articles of interest. To analyze heterogeneity, Higgins' I2 as well as prediction intervals and Egger's test were used to assess heterogeneity. The Newcastle-Ottawa standard ratings approach was used to assess the quality of observational studies. The ROBINS-I risk of bias algorithm was used to assess bias risks of randomized studies. This meta-analysis evaluated 8 studies in total. Over the follow-up time frame, patients who used SGLT2i had substantially lower systolic pulmonary artery pressure and higher tricuspid annular plane systolic excursion values (mean difference [MD] = -5.23 [-7.81; -2.66] and, MD = 1.47 [1.01; 1.93]; P <0.01, respectively). There was no significant difference in RVS' values between follow-up and baseline (MD = 1.54 [-0.19; 3.26]; P = 0.08). However, as compared to the baseline period, fractional area contraction values were substantially larger at the end of the follow-up (MD = 5.52 [4.23; 6.82]; P <0.01). To the best of our knowledge, this is the first meta-analysis assessing the impact of SGLT2i on RV function in HF patients. Our findings suggest that SGLT2i may improve RV performance in HF patients.

Septal annular dilation in chronic ovine functional tricuspid regurgitation

Annular reduction with prosthetic rings represents the current surgical treatment of functional tricuspid regurgitation (FTR). However, alterations of annular geometry and dynamics associated with FTR are not well characterized. FTR was induced in 29 adult sheep with either 8 weeks of pulmonary artery banding (PAB, n=15) or 3weeks of tachycardia-induced cardiomyopathy (TIC, n=14). Eight healthy sheep served as controls (CTL). At the terminal procedure, all animals underwent sternotomy, epicardial echocardiography, and implantation of sonomicrometry crystals on the tricuspid annulus (TA) and right ventricular free wall while on cardiopulmonary bypass. Simultaneous hemodynamic, sonomicrometry, and echocardiographic data were acquired after weaning from cardiopulmonary bypass and stabilization. Annular geometry and dynamics were calculated from 3-dimensional crystal coordinates. Mean FTR grade (0-4) was 3.2± 1.2 and 3.2± 0.5 for PAB and TIC, respectively, with both models of FTR associated with similar degree of right ventricular dysfunction (right ventricular fractional area contraction 38± 7% and 37± 9% for PAB and TIC, respectively). Left ventricular ejection fraction was significantly reduced in TIC versus baseline (33± 9%, vs 58± 4%, P=.0001). TA area was 651± 109 mm2, 881± 242 mm2, and 995± 232mm2 for CTL, FTR, and TIC, respectively (P=.006) with TA area contraction of 16.6± 4.2%, 11.5± 8.0%, and 6.0± 4.0%, respectively (P=.003). Septal annulus increased from 33.8± 3.1 mm to 39.7± 6.4 mm and 43.1± 3.2mm for CTL, PAB, and TIC, respectively (P<.0001). Ovine FTR was associated with annular dilation and reduced annular area contraction. Significant dilation of septal annulus was observed in both models of FTR. As tricuspid rings do not completely stabilize the septal annulus, continued remodeling may contribute to recurrent FTR after repair.

Herbal Extract from Codonopsis pilosula (Franch.) Nannf. Enhances Cardiogenic Differentiation and Improves the Function of Infarcted Rat Hearts.

Background: The roots of Codonopsis pilosula (Franch.) Nannf. have been used in traditional Chinese medicine for treating cardiovascular disease. In the current study, we aimed to discover herbal extracts from C. pilosula that are capable of improving cardiac function of infarcted hearts to develop a potential therapeutic approach. Methods: A mouse embryonic stem (ES) cell-based model with an enhanced green fluorescent protein (eGFP) reporter driven by a cardiomyocyte-specific promoter, the α-myosin heavy chain, was constructed to evaluate the cardiogenic activity of herbal extracts. Then, herbal extracts from C. pilosula with cardiogenic activity based on an increase in eGFP expression during ES cell differentiation were further tested in a rat myocardial infarction model with left anterior descending artery (LAD) ligation. Cardiac function assessments were performed using echocardiography, 1, 3, and 6 weeks post LAD ligation. Results: The herbal extract 417W from C. pilosula was capable of enhancing cardiogenic differentiation in mouse ES cells in vitro. Echocardiography results in the LAD-ligated rat model revealed significant improvements in the infarcted hearts at least 6 weeks after 417W treatment that were determined based on left ventricle fractional shortening (FS), fractional area contraction (FAC), and ejection fraction (EF). Conclusions: The herbal extract 417W can enhance the cardiogenic differentiation of ES cells and improve the cardiac function of infarcted hearts.

Risk factors of early right ventricular failure in patients undergoing LVAD implantation with intermediate Intermacs profile for advanced heart failure.

The clinical profile of left ventricular assist device (LVAD) candidates is rapidly changing, with increasing proportion of patients in more stable clinical conditions. However, early postoperative right ventricular failure (eRVF) is still one of the cornerstones associated with increased mortality and the preoperative recognition of associated risk factors remains challenging. The aim of this study was to identify predictive parameters for eRVF after LVAD implantation in patients with preoperative intermediate Intermacs (InM) risk profile 3-5. Preoperative laboratory, echocardiography, and right heart catheterization data collected from 80 patients with InM profile 3-5 before LVAD implantation were retrospectively tested with respect to their ability to predict the risk for eRVF after the implantation of a continuous-flow LVAD. Preoperative higher bilirubin and blood urea nitrogen (BUN) levels, higher Model for End-stage Liver Disease score, lower estimated glomerular filtration rate, and higher central venous pressure to pulmonary capillary wedge pressure ratio (CVP/PCWP) were associated to higher risk of eRVF. Regarding the echocardiographic assessment, higher end diastolic linear dimensions of the RV, higher basal end diastolic RV linear dimension to LV ratio, severe tricuspid regurgitation, lower tricuspid annular plane systolic excursion, and lower RV fractional area contraction identified patients with higher risk for eRVF. In the multivariable analysis, a CVP/CPWP > 0.55 (odds ratio [OR]: 4, 95% confidence interval [CII]: 1.4-11.8;P = .01) and BUN > 44.5 mg/dL (OR: 6.6, 95% CI: 1.51-23; P = .011) independently predicted the risk of eRVF. Preoperative BUN > 44.5 mg/dL and CVP/PCWP > 0.55 are associated to an increased risk of eRVF following LVAD implantation in intermediate InM patients.

Fine-tuning management of the Heart Assist 5 left ventricular assist device with two- and three-dimensional echocardiography.

SummaryIntroduction:Left ventricular assist device (LVAD) implantation is a viable therapy for patients with severe end-stage heart failure, providing effective haemodynamic support and improved quality of life. The Heart Assist 5 (Micromed Cardiovascular Inc, Houston, TX) continuous-flow LVAD has been on the market in Europe since May 2009.Methods:We evaluated nine Heart Assist 5 LVAD patients with two- and three-dimensional transthoracic echocardiographic (TTE) and transoesophageal echocardiographic (TEE) parameters between December 2011 and December 2013. The pre-operative TTE LVAD evaluations included left ventricular (LV) function and structure, quantification of right ventricular (RV) function and tricuspid regurgitation (TR), assessment of aortic and mitral regurgitation, and presence of patent foramen ovale and intra-cardiac clots. Peri-operative TEE determined the inflow cannula and septum position, and assessed the de-airing process while weaning from cardiopulmonary bypass. Post-operative serial follow-up TTE showed the surgical results of LVAD implantation, determined the overall structure and function of the LV, RV and TR, and observed the inflow and outflow cannula position.Results:Nine patients who had undergone Heart Assist 5 LVAD implantation and had been followed up for more than 30 days were included in this study. Eight patients had ischaemic cardiomyopathy and one had adriamycin-induced cardiomyopathy. Pre-implantation data: the mean age of the patients was 52 ± 13 (34–64) years, mean body surface area (BSA) was 1.8 ± 0.2 (1.6–2.0) m2, mean cardiac index (CI) was 2.04 ± 0.4 (1.5–2.6) l/min/m2, mean cardiac output (CO) was 3.7 ± 0.7 (2.6–4.2) l/min, mean ejection fraction (EF) was 23 ± 5 (18–28)%, and right ventricular fractional area contraction (RVFAC) was 43 ± 9 (35–55)%. One patient had aortic valve replacement (AVR) during the LVAD implantation, and excess current alarms and increased power were suspected to be caused by a possible thrombus. Close follow up with TTE studies were carried out to clear the LV of thrombus formation, and the inflow cannula position was checked to maintain the septum in the midline, so preventing the suction cascade. Four patients were followed up for more than two years, and two were followed up for more than a year. Three patients died due to multi-organ failure. Follow-up speed-change TTE studies of six patients showed that the mean speed was 9 800 ± 600 (9 500–10 400) rpm, and mean CO was 4.7 ± 0.3 (4.3– 5.0) l/min during the three-month post-implant period.Conclusion:We believe that TTE can play a major role in managing LVAD patients to achieve optimal settings for each patient. A large series is mandatory for assessment of echocardiographic studies on Heart Assist 5 LVAD.

Cardiac Ultrasonography in the critical care setting: a practical approach to asses cardiac function and preload for the "non-cardiologist".

Cardiac ultrasonography has become an indispensible tool in the management of hemodynamically unstable critically ill patients. Some consider it as the modern stethoscope. Echocardiography is non-invasive and safe while the modern portable devices allow to be used at the bedside in order to provide fast, specific and vital information regarding the hemodynamic status, as well as the function, structure and anatomy of the heart. In this review, we will give an overview of cardiac function in general followed by an assessment of left ventricular function using echocardiography with calculation of cardiac output, left ventricular ejection fraction (EF), fractional shortening, fractional area contraction, M mode EF, 2D planimetry and 3D volumetry. We will briefly discuss mitral annulus post systolic excursion (MAPSE), calculation of dP/dt, speckle tracking or eyeballing to estimate EF for the experienced user. In a following section, we will discuss how to assess cardiac preload and diastolic function in 4 simple steps. The first step is the assessment of systolic function. The next step assesses the left atrium. The third step evaluates the diastolic flow patterns and E/e' ratio. The final step integrates the information of the previous steps. Echocardiography is also the perfect tool to evaluate right ventricular function with tricuspid annular plane systolic excursion (TAPSE), tissue Doppler imaging, together with inferior vena cava dimensions and systolic pulmonary artery pressure and right ventricular systolic pressure measurement. Finally, methods to assess fluid responsiveness with echocardiography are discussed with the inferior vena cava collapsibility index and the variation on left ventricle outflow tract peak velocity and velocity time integral. Cardiac ultrasonography is an indispensible tool for the critical care physician to assess cardiac preload, afterload and contractile function in hemodynamically unstable patients in order to fine-tune treatment with fluids, inotropes and/or vasopressors.

Influence of Increased Left Ventricular Myocardial Mass on Early and Late Mortality After Cardiac Surgery

Background Increased left ventricular mass (LVM) is a well-recognized predictor of cardiovascular morbidity and mortality in epidemiological studies, but its impact on mortality after cardiac surgery is poorly defined. We hypothesized that patients with increased LVM index (LVMI) were more likely to have greater 30 day and 1 yr mortality. Methods With IRB approval, intraoperative transoesophageal echocardiography images of 844 cardiac surgical patients were reviewed. LVMI was calculated using the American Society of Echocardiography recommended formula. Outcome variables studied were 30 day and 1 yr mortality. Results Mortality within 30 days occurred in 28 patients (3.3%) and within 1 yr in 91 patients (10.8%). An almost linear relationship was found between increasing LVMI and the risk of mortality within 30 days of cardiac surgery. The odds ratio (OR) of dying within 30 days of surgery was 1.15 (95% confidence interval 1.01–1.31) per 20 g m−2 increase in LVMI. This finding remained statistically significant in multivariate analysis controlling for the effects of age, weight, gender, surgery type, LV function, and functional status [OR=1.36 (1.11–1.66) per 20 g m−2 increase]. Increased LVMI was not found to be a statistically significant predictor of 1 yr mortality. Conclusions Increased LVMI, but not LV systolic function as measured by the fractional area of contraction (FAC) was identified as a strong independent predictor of perioperative mortality after adult cardiac surgery. The relationship between LVMI and risk of 30 day mortality was nearly linear. Furthermore, decreased FAC, and not LVMI, was a strong independent predictor of 1 yr mortality.

MiR‐17 targets tissue inhibitor of metalloproteinase 1 and 2 to modulate cardiac matrix remodeling

We aimed to investigate the role of miR-17 in cardiac matrix remodeling following myocardial infarction (MI). Using real-time PCR, we quantified endogenous miR-17 in infarcted mouse hearts. Compared with related microRNAs, miR-17 was up-regulated most dramatically: 3.7-fold and 2.4-fold in the infarct region 3 and 7 d post-MI, respectively, and 2.4-fold in the border zone at d 3 compared to sham control (P<0.01). Chimeric luciferase reporter constructs were cloned for miR-17 target validation. miR-17 targeted the 3'-UTR of TIMP2 and the protein coding region of TIMP1. The miR-17 mimic decreased TIMP2 (P<0.01) and TIMP1 (P<0.05) protein expression compared with the scrambled control. Inhibition of endogenous miR-17 by in vivo antagomir delivery enhanced TIMP2 (P<0.01) and TIMP1 (P<0.05) protein expression compared to the mismatch group, decreased MMP9 activity (P<0.05), reduced infarct size as early as 7 d post-MI (P<0.05), and improved cardiac function (fractional shortening and fractional area contraction, P<0.05) at d 21 and 28 post-MI. Transgenic mice overexpressing miR-17 in the heart confirmed the deleterious role of miR-17 in matrix modulation. Our study suggests that miR-17 participates in the regulation of cardiac matrix remodeling and provides a novel therapeutic approach using miR-17 inhibitors to prevent remodeling and heart failure after MI.

Influence of increased left ventricular myocardial mass on early and late mortality after cardiac surgery

Increased left ventricular mass (LVM) is a well-recognized predictor of cardiovascular morbidity and mortality in epidemiological studies, but its impact on mortality after cardiac surgery is poorly defined. We hypothesized that patients with increased LVM index (LVMI) were more likely to have greater 30 day and 1 yr mortality. With IRB approval, intraoperative transoesophageal echocardiography images of 844 cardiac surgical patients were reviewed. LVMI was calculated using the American Society of Echocardiography recommended formula. Outcome variables studied were 30 day and 1 yr mortality. Mortality within 30 days occurred in 28 patients (3.3%) and within 1 yr in 91 patients (10.8%). An almost linear relationship was found between increasing LVMI and the risk of mortality within 30 days of cardiac surgery. The odds ratio (OR) of dying within 30 days of surgery was 1.15 (95% confidence interval 1.01-1.31) per 20 g m(-2) increase in LVMI. This finding remained statistically significant in multivariate analysis controlling for the effects of age, weight, gender, surgery type, LV function, and functional status [OR=1.36 (1.11-1.66) per 20 g m(-2) increase]. Increased LVMI was not found to be a statistically significant predictor of 1 yr mortality. Increased LVMI, but not LV systolic function as measured by the fractional area of contraction (FAC) was identified as a strong independent predictor of perioperative mortality after adult cardiac surgery. The relationship between LVMI and risk of 30 day mortality was nearly linear. Furthermore, decreased FAC, and not LVMI, was a strong independent predictor of 1 yr mortality.

Infusion of low-dose vasopressin improves left ventricular function during separation from cardiopulmonary bypass: A double-blind randomized study

We aimed to investigate whether low-dose vasopressin administered to patients undergoing coronary artery bypass grafting (CABG) surgery with preexisting mild to moderate systolic dysfunction can produce sustained improvement in cardiac function. This double-blind randomized study was conducted in a hospital where a single anesthetic and surgical team performed elective CABG. Twenty patients aged 32-61 years who underwent elective CABG between January 2007 and December 2007 were enrolled in this study. The patients randomly received either vasopressin 0.03 IU/min (Group A) or normal saline (Group B) in equal volume for 60 min after cardiopulmonary bypass (CPB). The cardiac output, cardiac index, stroke volume index, fractional area of contraction and systemic vascular resistance index were significantly higher in Group A than in Group B. Adrenaline (mean dose: 0.06 μg/kg x min-1) was required in seven patients from Group B but in none of the Group A patients on initial separation from CPB (P< 0.05). Of the 10 patients in Group B, five required phenylepherine to maintain the mean arterial pressure (MAP) >65 mmHg, whereas none of the Group A patients required phenylephrine for MAP regulation (P< 0.05). We conclude that Infusion of low-dose vasopressin for patients with mild to moderate left ventricular systolic dysfunction during separation from CPB is beneficial for the postoperative hemodynamic profile, reduces the catecholamine doses required and improves left ventricular systolic function.

Abstract 2935: Clinical-Instrumental Characteristics and Prognosis in Patients with Arrhythmogenic Right Ventricular Cardiomyopathy: 30 Years of Experience in a Referral Center

There are few studies regarding the clinical and instrumental presentation of Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC); all available data derive from few specialized centers. We sought to describe clinical characteristics, instrumental findings and prognosis in a large cohort of patients (pts) with an ARVC diagnosis. From 1976 to 2006 all pts matching ARVC diagnostic criteria were enrolled in the Heart Muscle Disease Registry of Trieste and underwent a structured diagnostic protocol and follow-up. 104 pts were studied, 66% males, mean age 33±13 years; 84% were symptomatic at enrolment (mean duration 44±67 months); 75% had symptomatic arrhythmias (43% with previous sustained ventricular tachycardia or ventricular fibrillation (SVT/VF)), 36% syncope, 20% heart failure (12% in NYHA class III-IV). Familial ARVC were present in 46% of pts. ECG was abnormal in 72% (right bundle branch block 25%; epsilon potentials 15%; anterior negative T waves 51%; QRS dispersion &gt;40ms 11%). At signal averaged ECG late potentials were present in 58% of pts. At 2D echo, mean right ventricle (RV) end-diastolic area was 30± 8 cm2 and RV fractional area contraction (FAC) 30±13%; RV aneurysms were present in 67%. RV systolic dysfunction (defined as FAC&lt;40%) was present in 78%, characterized severe (FAC &lt;30%) in 48%. Left ventricular systolic dysfunction was present in 27% of pts. Stress test was interrupted in 11% of cases for ventricular arrhythmias (55% SVT/VF). RV fibrofatty tissue was present in 52% of Nuclear Magnetic Resonance and in 59% of RV endomyocardial biopsy (performed respectively in 24 and 27% of pts). During a mean follow-up of 132±89 months, 3 pts were lost; 20 out of the remaining 101 pts (20%) experienced death/heart transplantation, 6 (3%) died for refractory HF; 4 pts (2%) underwent heart transplantation (HT); 6 pts (3%) died suddenly; one (0.5%) for extracardiac disease and 3 (1.6%) for unknown reason. Ten-year cumulative survival free from HT was 57%. In our population ARVC presentation was characterized by symptomatic, frequently sustained ventricular arrhythmias. Notably, LV involvement was present in approximately one third of pts at enrolment. In the long term, the overall prognosis was severe.

Is myocardial adrenergic responsiveness depressed in human septic shock?

To assess left ventricular (LV) contractile function and adrenergic responsiveness in septic patients. We used echocardiographically defined fractional area of contraction (FAC), and LV area to end-systolic arterial pressure estimates of end-systolic elastance (E'es) and its change in response to dobutamine (5 microg/kg/min) in 10 subjects in septic shock admitted to an intensive care unit of an academic medical center. Subjects were studied on admission and again at both 5 days and 8-10 days after admission. Three of the 10 subjects died as a result of their acute process, while the others were discharged from hospital. Nine out of 10 subjects required intravenous vasopressor therapy on day 1, while only 1 of 9 subjects required vasopressor support at day 5. LV end-diastolic area (EDA) increased from day 1 to day 5 and days 8-10 (p<0.05), but neither FAC nor E'es was altered by time (EDA 15.7+/-5.8, 21.4+/-5.1, and 19.4+/-5.6 cm2; FAC 0.46+/-0.19, 0.50+/-0.20, and 0.48+/-0.15%; E'es 21.6+/-12.6, 23.2+/-8.5, and 19.2+/-6.3 mmHg/cm2, mean+/-SD, for days 1, 5 and 8-10 respectively). Although dobutamine did not alter E'es on day 1 or day 5, E'es increased in all of the 5 subjects studied on days 8-10 (p<0.05). Adrenergic hyporesponsiveness is present in septic shock and persists for at least 5 days into recovery, resolving by days 8-10 in survivors.

Brain natriuretic peptide: A marker of myocardial dysfunction and prognosis during severe sepsis.

To investigate the value of brain natriuretic peptide plasma levels as a marker of systolic myocardial dysfunction during severe sepsis and septic shock. Prospective observational study. Intensive care unit. A total of 34 consecutive patients with severe sepsis (nine patients) or septic shock (25 patients) without previous cardiac, respiratory, or chronic renal failure. None. Myocardial systolic performance was assessed by fractional area contraction (FAC) using echocardiography performed on days 2 (FACD2) and 8. Plasma levels of brain natriuretic peptide were measured at days 1-4 and 8 after the beginning of severe sepsis. Among 34 patients (Simplified Acute Physiology Score II, 43 +/- 2.5), 15 (44%) presented with initial myocardial dysfunction (FACD2 < 50%). Lungs were the origin of sepsis in 65% of patients. The 28-day mortality was 29%. Comparisons were performed between patients with (FACD2 < 50%) and without (FACD2 > or = 50%) myocardial dysfunction. Plasma levels of brain natriuretic peptide were significantly higher in patients with FACD2 < 50% than in those with FACD2 > or = 50% (p <.05) from day 2 to day 4. Brain natriuretic peptide levels were also significantly higher on days 2 and 3 in patients who died during their intensive care unit stay (p <.05). Systolic myocardial dysfunction is present in 44% of patient with severe sepsis or septic shock. In this setting, brain natriuretic peptide seems useful to detect myocardial dysfunction, and high plasma levels appear to be associated with poor outcome of sepsis, but further studies are needed.

Early and late results of left ventricular reshaping by passive cardiac-support device in canine heart failure

We tested whether the CardioClasp, a passive non-blood-contacting device could decrease excessive geometric burden in dilated cardiomyopathy and improve left ventricular systolic function and contractility by reshaping the left ventricle (LV) and by decreasing LV wall stress (LVWS) without decreasing arterial blood pressure. In mongrel dogs (n = 6, the early group; n = 6, the chronic group; 25-27 kg), 4 weeks of rapid right ventricular pacing (210 to 240 bpm) induced dilated cardiomyopathy with heart failure. In the early group, we used hemodynamic data and echocardiography to evaluate LV systolic function immediately after placing the CardioClasp device. In the chronic group, we also evaluated LV systolic function immediately after placing the device on dilated hearts and then left the device in place for 30 days. At the end of 30 days, before explantation of the device, we again assessed LV systolic function. We measured fractional area of contraction (FAC), LVWS, and hemodynamic data in both groups. In the early group, use of the CardioClasp device decreased the LV end-diastolic anterior-to-posterior dimension by 27.8% +/- 2.6% at implantation (p < 0.05). In the chronic group, use of the CardioClasp decreased the LV end-diastolic anterior-to-posterior dimension by 19.4% +/- 2.0% at implantation (p < 0.05) and by 22.0% +/- 3.10% at explantation (p < 0.05). Use of the CardioClasp did not alter LV end-diastolic and peak pressure, LV dP/dts, or cardiac output at implantation or at explantation. In the early group, use of the CardioClasp decreased the LVWS by 43.4% +/- 3.1% at implantation (p < 0.05). In the chronic group, LVWS decreased by 28.8% +/- 2.1% at implantation (p < 0.05) and by 43.3% +/- 5.2% at explantation (p < 0.05). In the early group, FAC increased significantly, by 28.9% +/- 7.8% at implantation (p < 0.05). In the chronic group, FAC increased significantly, by 18% +/- 12% at implantation (p < 0.05) and by 19% +/- 12% at explantation (p < 0.05). As expected, use of the CardioClasp device increased FAC and decreased LVWS by reshaping the LV. Use of the CardioClasp device maintained cardiac output and arterial pressure. In 30-day experiments, the increased FAC and decreased LVWS were maintained at explantation.

CardioClasp changes left ventricular shape acutely in enlarged canine heart.

In dilated cardiomyopathy (DCM), eliminating or reducing extra-geometric burden to the myocardial cells would directly reduce myocardial wall stress leading to improved LV systolic performance. In acute experiments, we tested whether a passive non-blood contacting CardioClasp device, which employs two indenting bars to reshape the left ventricle (LV), could reduce extra-geometric burden, LV wall stress (LVWS) and improve LV systolic function and contractility without decreasing arterial blood pressure. In mongrel dogs (n = 5), 4 weeks of right ventricular pacing (210-220-230-240 ppm) induced DCM with severe heart failure. After placing the CardioClasp device, LV performance was evaluated immediately by measuring hemodynamics, echocardiography, and Sonometrics crystal data. Eleven sonometric crystals were placed into endocardial positions (8 in anterior, posterior, mid-anterior, mid-posterior, apex, base, free and septal wall) and in myocardial (2 as regional) and epicardial (1) positions to assess the LV end-systolic pressure-segment length relationships (ESPSR) and cross-sectional area (ESPAR) relationship. CardioClasp decreased the LV end-diastolic anterior-posterior (A-P) dimensions at two levels (15% and 25%). With CardioClasp, LVWS decreased from 93.1 +/- 7.2 to 59.1 +/- 3.2 g/cm2 (P < 0.05) and fractional area of contraction (FAC) increased from 27.6 +/- 3.8 to 33.1 +/- 3.7% (P < 0.01). Peak LV and arterial pressures, LV +dP/dt, LV -dP/dt, and cardiac output were unaltered with CardioClasp. CardioClasp placement significantly increased the slopes of LV pressure versus anterior-posterior segment relationship from 7.3 +/- 0.6 to 15.8 +/- 1.8 mmHg/mm and septal-free wall segment relationship from 6.3 +/- 0.9 to 9.8 +/- 0.5 mmHg/mm. At both 15% and 25% LV A-P dimension reductions, the slopes of ESPAR showed significant steepening and increased from 10.1 +/- 0.7 (baseline) to 15.5 +/- 1.7 (15% reduction) and 19.0 +/- 1.4 mmHg/cm2 (25% reduction). The larger the reduction, the greater was the steepening of the slopes of ESPSR and ESPAR. CardioClasp reduced LV diameter and thereby decreased LVWS and increased FAC. CardioClasp was able to reshape the left ventricle, while preserving the contractile mass, which increased the slopes of ESPSR and ESPAR. This reshaping was associated with maintained systolic pressures, cardiac output, and increased contractility.

CardioClasp: a new passive device to reshape cardiac enlargement.

In dilated heart failure, geometric distortions place an extra load on the myocardial cells. If this extra burden can be eliminated, the myocardial wall stress would decrease leading to improved systolic ventricular performance. In a dilated heart failure model, we wanted to see whether the CardioClasp (which uses two indenting bars to reshape the left ventricle [LV] as two widely communicating "lobes" of reduced radius) could improve systolic performance by passively reshaping the LV and reducing the wall stress. In mongrel dogs (n = 7; 25-27 kg), rapid ventricular pacing (210 ppm 1st week to 240 ppm 4th week) induced dilated heart failure. After 4 weeks, LV performance was evaluated at baseline and with the CardioClasp by measuring LV end-diastolic and peak LV systolic pressure, LV +dP/dt, LV -dP/ dt, and cardiac output. With the Clasp on, LV wall stress was reduced to 58.6+/-3.5 from 108.3+/-8.2 g/cm2. The fractional area of contraction (FAC) with the Clasp on (28.4+/-4.4) was significantly increased (p < 0.05) from baseline (20.8+/-4.6) and consistent with improved systolic performance. Cardiac output, LV peak systolic and end-diastolic pressures, and regional myocardial blood flow were unaltered. The Clasp was able to acutely reshape the left ventricle, while preserving the contractile mass, and reduced the tension on the myocardial cells and increased the fractional area of contraction without decreasing the systolic blood pressure.

Cardiovascular responses to repetitive defibrillation during implantable cardioverter-defibrillator testing

To study the effects of electrical applications and subsequent postshock hypotension on myocardial performance and vascular tone during implantable cardioverter-defibrillator (ICD) placement. Prospective, blinded, observational investigation. Single, university-affiliated institution. Twenty patients undergoing elective ICD placement and testing under general anesthesia. None. Serial measurements were made of hemodynamic variables, left ventricular end-systolic (ESA) and end-diastolic (EDA) areas, fractional-area-of-contraction (FAC), time of hypoperfusion (when mean arterial pressure < or =50 mmHg postshock), and applied conversion energy. Multiple linear regression was performed to determine correlations among collected variables, and repeated measures analysis of variance was used to compare mean values. Minimal changes were detected in mean values of arterial, pulmonary, and central venous pressures; cardiac output; heart rate; and mixed venous saturation during repeated testing. Percentage changes in cardiac index (CI) rose and systemic vascular resistance index (SVRI) fell, however, as the number of shocks increased, reaching significance at the seventh and eighth shocks (v baseline; both p = 0.015). The percentage change in CI was linearly related to hypoperfusion time and accumulated energy (%deltaCI = 1.553 + [0.068 x sigma hypoperfusion time [sec]], r = 0.92, p < 0.001; %deltaCI = 0.326 + [0.125 x sigma Energy [J]], r = 0.94, p < 0.001). The percentage change in SVRI was inversely related to hypoperfusion time and accumulated energy (%deltaSVRI = 2.195 - [0.122 x sigma energy [J]], r = 0.79, p = 0.004; %deltaSVRI = 0.542 - [0.0634 - sigma hypoperfusion time [sec]], r = 0.73, p = 0.01). Echocardiographic EDA, ESA, and FAC were not significantly changed but showed substantial variability. Hemodynamic stability was generally well maintained during ICD placement and testing. Increases in CI were associated with concurrent reductions in systemic afterload, rather than enhanced FAC. Increasing postshock hypotension and applied energy were associated with decreases in CI and systemic afterload. Insignificant, but highly variable, changes were noted echocardiographically.

CONTRACTILE RECOVERY BY CARDIOCLASP DEVICE IN HEART FAILURE

We tested whether a non-blood contact device (CardioClasp) can improve and recover contractile myocardial function in heart failure during dobutamine stress testing (DST). In dogs (n=6), rapid pacing (210–240 ppm) induced heart failure. In 4 dogs, CardioClasp was implanted after 4 weeks pacing and kept for 30-days. The other 2 dogs served as sham. All had post-op 190 ppm maintenance pacing. After 30 days of CardioClasp or sham implant, all the animals underwent dobutamine challenge by 2.5, 5, 10, 20, and 40 μg/kg/min and evaluated by echocardiography and hemodynamic meaurements. CardioClasp decreased LV anterior-posterior dimension by 23.4 ± 1.3% during implant. With DST, heart rate, peak systolic pressure, CO, and fractional area of contraction (FAC) were increased in the both groups. With DST, FAC, CO, improvements of wall motion and thickening were observed in both groups although were prominent in CardioClasp implanted animals.TableDuring 1-month chronic implant, CardioClasp was able to maintain FAC and CO with unaltered arterial pressure. In these preliminary experiments with dobutamine challenge, CardioClasp was able to show improved and maintained myocardial function after month-long implant.

Early preload adaptation in septic shock? A transesophageal echocardiographic study.

An accepted concept in septic shock is that preload adaptation by acute left ventricular dilatation, when occurring spontaneously or with the aid of volume loading, permits maintenance of an adequate cardiac output, leading to final recovery. From a physiologic point of view, this concept appears debatable because a normal pericardium exerts a restraining action on a normal heart. During a 26-month period, the authors investigated, by transesophageal echocardiography, 40 patients hospitalized in their unit for an episode of septic shock. Transesophageal echocardiography was performed in the first hours after admission, proceeded by correction of any hypovolemia, and stabilization of arterial pressure by vasoactive agent infusion if necessary. Left ventricular dimensions were obtained in long- and short-axis views, permitting calculation of left ventricular ejection fraction (long axis) and fractional area contraction (short axis). Stroke index was simultaneously measured by the Doppler technique. Stroke index was strongly correlated with both echocardiographic left ventricle ejection fraction (r = 0.75; P < 0.0001) and left ventricle fractional area contraction (r = 0.76; P < 0.0001), whereas it was independent of echocardiographic left ventricle diastolic dimensions. The transesophageal echocardiography study was unable to confirm the reality of the concept of early preload adaptation by left ventricular dilatation in septic shock. Conversely, because left ventricular volume always remained in a normal range after correcting hypovolemia, systolic function was the unique determinant of stroke index in septic shock.