BACKGROUND:Transcatheter aortic valve replacement (TAVR) is evolving as a preferred treatment option for severe aortic stenosis. While self-expanding valves (SEV) are associated with lower long-term mean gradients (MG), the timing and mechanisms of gradient changes across valve types remain unclear. AIMS:To evaluate the timing and extent of post-TAVR mean gradient changes across valve types, sizes, and calcium burden. METHODS:We conducted a retrospective analysis of 288 patients who underwent TAVR. MG was measured using echocardiography immediately post-deployment (TEE), on Day 1, and at 1-2 months postprocedure (TTE). Early ΔMG was defined as the difference between post-deployment TEE and Day 1 TTE; intermediate ΔMG as the difference between post-deployment TEE and 1-month TTE. Comparisons were performed by valve type, valve size, and calcium score using chi-square tests for categorical variables and t-tests for continuous variables. Logistic regression was used to adjust for potential confounding factors. RESULTS:Patients receiving balloon-expandable valves (BEV) had significantly greater early ΔMG (7.65 ± 0.75 mmHg) compared to SEV (2.55 ± 0.65 mmHg; p < 0.0001). Intermediate ΔMG was also higher in BEV (8.0 ± 0.7 vs. 2.2 ± 1.1 mmHg; p < 0.0001). Smaller valve sizes, particularly the 23 mm BEV, were associated with the largest gradient increases. Calcium score had a minimal impact on early MG and no effect on intermediate MG. CONCLUSIONS:Hemodynamic changes begin within the first 24 h after TAVR, with BEV showing more pronounced early and intermediate increases in MG compared to SEV. These findings suggest that valve type and size are major drivers of post-TAVR gradient behavior, whereas calcium burden plays a limited role.

With the aging of the US population and increasing prevalence of both diabetes and coronary artery disease (CAD), the number of interventional coronary and peripheral arterial procedures has markedly increased in an attempt to prevent morbid and mortal events. Unfortunately, the cardiovascular mortality of the diabetic patient remains high; the risk of a myocardial infarction (MI) at 7 years is equivalent for the diabetic without CAD and the nondiabetic who has already suffered an MI (1). It has been estimated that the spontaneous risk of MI in diabetics with three-vessel disease is 10% to 15% per year (2). Total mortality after this MI is higher than in the nondiabetic population. Over the last two decades, the number of diabetics undergoing percutaneous coronary intervention (PCI) has doubled, and the age, lesion complexity, and proportion of unstable patients has increased (3).

Introduction: The maximal allowable contrast dose (MACD = 5 × body weight/serum creatinine) is an empiric equation that has been used and validated in several studies to mitigate the risk of contrast-induced acute kidney injury (CI-AKI). However, coefficient 5 (referred to as factor K) was empirically devised and never disputed. The aim of this study was to refine the MACD equation for the prediction of CI-AKI following percutaneous coronary interventions (PCIs). Methods: This is a single-center, retrospective cohort study of adults undergoing PCI. Electronic medical records were reviewed to identify patients who underwent PCI between 2010 and 2019, derived from the National Cardiovascular Data Registry Cath-PCI registry for our hospital. Factor K (defined as contrast volume × serum creatinine/body weight) was calculated for every patient. A receiver operating characteristic (ROC) curve was constructed, and the Youden index was used to identify the optimal cut-off value for factor K in predicting severe (stages 2–3) CI-AKI. Results: Of the 3,506 patients undergoing PCI, 255 (7.2%) developed CI-AKI, and 68 (26.7%) of the 255 experienced severe AKI. Factor K predicted all-stage CI-AKI (area under the ROC curve 0.649; 95% CI 0.611, 0.686) but had better performance for predicting severe (stages 2–3) AKI (0.736; 95% CI 0.674, 0.800). The optimal cut-off value for factor K in predicting severe CI-AKI was 2.5, with a corresponding sensitivity of 68.7% and specificity of 70.5%. On subgroup analyses, optimal cut-off values for factor K for high-risk groups were not significantly different from those of low-risk groups. Conclusion: Our study indicates that factor K in the MACD equation is an independent risk factor for the development of severe CI-AKI, with an optimal cut-off value of 2.5. If our findings are validated, the MACD equation should be revised to incorporate the coefficient of 2.5 instead of 5.

IntroductionIntravenous (IV) loop diuretics are the mainstay for treatment of acute decompensated heart failure (ADHF). Activation of the renin-angiotensin system with diuresis can result in intravascular volume depletion despite total volume overload. Diuretic resistance and acute kidney injury can quickly ensue.HypothesisBased on RenalGuard device data, we hypothesized that co-administration of IV fluids (IVF) and diuretics will maintain plasma filling, resulting in preserved renal function and more effective diuresis. Feasibility of carrying out these actions manually throughout the 24-hour period was also assessed.MethodsFour patients (pts) admitted with ADHF refractory to IV diuretics were identified and received furosemide infusion. Fluid loss limit (FLL) was assessed hourly and replacement IVF was given to replace excess fluid removed or to meet the FLL. After 24 hours, IVF repletion was stopped. Hemodynamics, urine output, fluid intake, renal function, and plasma/urine electrolytes were monitored.ResultsWith co-administration of IVF and diuretics, pts achieved a greater net fluid loss during the treatment period. Average (avg) net fluid loss for the 4 pts was 512 mL greater during the 24h treatment period compared to the 24h prior to treatment. Renal function improved in all 4 pts. After 24 hrs of treatment, avg creatinine change was -0.3 mg/dL, avg BUN change was -5 mg/dL, and avg eGFR increase was 7.3 mL/min. After IVF were discontinued, renal function declined. On physical exam, all 4 pts showed improvement in JVD, and lower extremity edema became less tense. In the setting of hourly adjustments of IVF/diuretics and monitoring of hemodynamics/labs, a 1:1 nurse to patient ratio was required for the duration of the treatment period in addition to hourly evaluations by advanced practitioners.ConclusionsThis small feasibility study showed that simultaneous administration of IVF with diuretics to maintain intravascular volume protects and may improve kidney function as well as improve patient symptoms with more effective diuresis and decongestion. Though an effective way to diurese patients, manual titration of IVF/diuretics was tedious, time consuming, and required significant manpower, including physicians and nurses for hourly patient clinical assessments and determination of FLL. This therapy was effective but would benefit from automation of the delivery system due to the workload burden on healthcare providers. The REPRIEVE study utilizing the Reprieve system to guide diuretic therapy with co-administration of IVF will test this hypothesis further.

Background: The visual interpretation of an angiographic stenosis may not always reflect the physiological significance of a lesion. Fractional Flow Reserve (FFR) is a reliable index to assess the significance of a lesion during hyperemia. However, there are pitfalls that can lead to significant misinterpretation and adverse events. Objective: This study sought to evaluate the accuracy and predictability of the non-hyperaemic pressure ratio (NHPR) without hyperemic stimuli, compared to hyperemic FFR. Methods: We conducted a retrospective, multicenter study of 700 patients who underwent a pressure recording during coronary angiography using NHPR and FFR measurements. Receiver operator characteristic (ROC) curve was constructed. NHPR sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy test were calculated. The most accurate NHPR cutoff was determined. Results: Of the 700 procedures, 449 cases were included. By ROC analysis, the optimal cut-point for NHPR was 0.93 to predict an FFR of <= 0.80 with an overall diagnostic accuracy of 78.84%. The sensitivity of this NHPR cutoff was 85.06%, specificity of 75.59%, PPV of 64.53% and a NPV of 90.65%. There was an overall accuracy of about 80% for predicting nonhyperemic index (FFR < 0.80) using a cutoff of NHPR <= 0.93. Conclusions: The use of NHPR can be considered in certain clinical scenarios where adenosine is contraindicated or there are other challenges; with the knowledge that hyperemia might be necessary if there is any high clinical suspicion as it still remains the reference standard for diagnostic certainty.

Coronary Vasospasm (CV) commonly presents with chest pain and medical management is the first line of treatment. In refractory cases percutaneous coronary intervention (PCI) and even an ICD placement may be necessary. 40 year old female with bipolar disorder and CV treated with diltiazem and

Valve in valve (ViV) transcatheter procedures have emerged as a viable option for patients who are not candidates for a redo-procedure. We present a case who underwent ViV with an Edwards Sapien valve for severe aortic regurgitation from her bioprosthetic aortic valve with subsequent severe patient

Despite the number of TAVR devices implanted there exists no standardized timing for evaluation of the replacement valve's function. In the periprocedure time window, mean gradients and peak velocities have been noted to be abnormally low, which may suggest post deployment left ventricular stunning

Coronary artery disease is a major cause of mortality and morbidity in the world, and PCI and CABG account for over a million procedures performed annually in the USA. The goal of percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) is to achieve complete revascularization (CR) if at all possible. However, restenosis and stent thrombosis (ST) remain the Achilles heel of contemporary PCI with restenosis rates between 10 and 30% with bare metal stents to 5–15% after drug-eluting stents and ST rates of around 0.8 vs 1.2%, respectively. Routine angiography after revascularization seems theoretically attractive as this may allow intervention before clinical events occur. In this manuscript, we review the literature regarding routine angiography after PCI or CABG and its outcomes.

Unicuspid aortic valve (UAV) offers unique challenges to transcatheter aortic valve replacement (TAVR), due to asymmetric expansion and apposition of the prosthesis during implantation. Although TAVR in bicuspid is now a well described experience, TAVR in unicuspid valve has not yet been described. A challenging case is described with TAVR in UAV using a Edwards Sapiens prosthesis via transapical approach. © 2016 Wiley Periodicals, Inc.

A 30-year-old male presented to the emergency department complaining of chest pain. Workup revealed a large cardiac mass causing compression of the cardiac chambers as the cause of his chest discomfort. This mass was subsequently diagnosed as a cardiac synovial sarcoma. Cardiac synovial sarcomas are very rare, primary malignant tumors of the heart, accounting for less than one percent of all cardiac tumors (Lv et al.,2010, Talukder et al., 2010). While only a few cases have been documented in the literature, this particular case demonstrates the importance of the continued work up for etiology of chest pain once more common etiologies like coronary heart disease (CHD) have been excluded, independent of patient age or comorbidities.

Bilateral subclavian stenosis is a rare clinical condition. An interbrachial pressure difference of 15 mm Hg can raise suspicion for unilateral subclavian artery stenosis, but the diagnosis of bilateral subclavian artery stenosis can be challenging. We present a case of a 75-year-old woman who presented with refractory hypotension after surgery. Initial vitals revealed blood pressure in the 60s/50s mm Hg in both arms. Cardiopulmonary examination was remarkable for diminished pulses in all 4 extremities and audible carotid bruits. She continued to be hypotensive despite aggressive fluid resuscitation. Troponin T peaked at 0.24 ng/mL (reference < 0.04), and an echocardiogram revealed a reduction in ejection fraction (37% from 50%). Left and right heart catheterization demonstrated normal filling pressures and cardiac output. During the procedure, however, it was noted that the patient’s central blood pressure was 70–80 mm Hg higher than cuff pressures obtained in either arm. Selective angiography revealed 90% left subclavian ostial stenosis as well as 70% stenosis of the right subclavian artery.

Abstract Studies from us and others showed that mice with cardiomyocyte-specific overexpression of a dominant negative PI3Kp110α had smaller hearts but maintained normal cardiac function. Yet, these mice developed systolic heart failure in the presence of cardiac stress, such as chemotherapy drug doxorubicin and aortic stenosis. Currently, drugs targeting the PI3K pathway are being tested in clinical trials for cancer therapy. Therefore, it is important to assess the cardiac effects of pharmacological inhibition of this pathway. Here, we report that a dual PI3K-mTOR inhibitor, BEZ235 (BEZ), induced cardiac hypertrophy and subsequent heart failure in mice when it was used alone or in combination with doxorubicin. This effect of BEZ was associated with increased hepatic gluconeogenesis, hyperglycemia, hyperinsulinemia and increased activation of the IGFR/insulin receptor (IR) in the heart. In isolated cardiomyocyte culture, BEZ induced feedback activation of IGFR/IR, but this effect was negligible compared to the IGFR/IR activation in the presence of insulin. Injections of insulin in mice lowered blood glucose, improved glucose and pyruvate tolerance but further increased the activation of IGFR/IR in the heart and aggravated BEZ-induced cardiac dysfunction; whereas OSI-906, an IGFR/IR inhibitor, alleviated this cardiac dysfunction. In addition, low dose Metformin significantly prolonged survival and improved cardiac function in BEZ-treated mice. Taken together, these results identified hyperinsulinemia, a systematic effect of the drug, as one of the mechanisms of BEZ-induced cardiac hypertrophy, arguing animal studies are indispensable for evaluating drug toxicity. They also suggest that Metformin but not insulin should be considered for controlling hyperglycemia and preventing the cardiac side effects that may be caused by PI3K pathway inhibitors in clinic. Citation Format: Jillian Onufrak, Yongayo Yang, Juyong Lee, John Fuseler, Maoyun Sun, Sharath Sasi, J. Tyson McDonald, Lynn Hlatky, Robert L. Price, Joseph Carrozza, David Goukassian, Thomas K. Borg, James P. Morgan, Xinhua Yan. A dual PI3K-mTOR inhibitor induced cardiac hypertrophy in mice: Role of the insulin signaling. [abstract]. In: Proceedings of the AACR Special Conference: Targeting the PI3K-mTOR Network in Cancer; Sep 14-17, 2014; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(7 Suppl):Abstract nr A56.

We previously reported that a dual PI3K-mTOR inhibitor BEZ235 (BEZ) induced cardiac hypertrophy. Here, we investigated potential mechanisms. Methods: three month old FVB/n female mice were treated with BEZ for five weeks. Cardiac function was monitored by serial echocardiography during the treatment and hemodynamic measurements at the end of the study. Cell signaling was analyzed by RT-PCR, Western blotting and ELISA. Results: BEZ induced a dose-dependent increase of left ventricular (LV) wall thickness and systolic function. These were associated with increased hypertrophic markers ANP, BNP, β-MHC and α-skeletal actin in the heart. In addition, in chronic BEZ-treated mouse hearts, the activations of PI3Ks, mTOR and ERK were increased. We conducted further studies to understand these contradictory results. We found that BEZ induced an increase of hepatic gluconeogenesis gene expression which was associated with increased fasting glucose, increased serum insulin level, a worsened glucose and pyruvate tolerance and increased IGFR/Insulin receptor activation in the heart. Injections of insulin lowered blood glucose, improved glucose and pyruvate tolerance, but further aggravated BEZ-induced cardiac dysfunction. On the other hand, OSI-906 (an IGFR/IR inhibitor) normalized cardiac function in BEZ-treated mice. Conclusions: Chronic BEZ treatment induced cardiac hypertrophy may be caused by increased insulin receptor activation in the heart.

Previous epidemiologic data demonstrate that cardiovascular (CV) morbidity and mortality may occur decades after ionizing radiation exposure. With increased use of proton and carbon ion radiotherapy and concerns about space radiation exposures to astronauts on future long-duration exploration-type missions, the long-term effects and risks of low-dose charged particle irradiation on the CV system must be better appreciated. Here we report on the long-term effects of whole-body proton (1H; 0.5 Gy, 1 GeV) and iron ion (56Fe; 0.15 Gy, 1GeV/nucleon) irradiation with and without an acute myocardial ischemia (AMI) event in mice. We show that cardiac function of proton-irradiated mice initially improves at 1 month but declines by 10 months post-irradiation. In AMI-induced mice, prior proton irradiation improved cardiac function restoration and enhanced cardiac remodeling. This was associated with increased pro-survival gene expression in cardiac tissues. In contrast, cardiac function was significantly declined in 56Fe ion-irradiated mice at 1 and 3 months but recovered at 10 months. In addition, 56Fe ion-irradiation led to poorer cardiac function and more adverse remodeling in AMI-induced mice, and was associated with decreased angiogenesis and pro-survival factors in cardiac tissues at any time point examined up to 10 months. This is the first study reporting CV effects following low dose proton and iron ion irradiation during normal aging and post-AMI. Understanding the biological effects of charged particle radiation qualities on the CV system is necessary both for the mitigation of space exploration CV risks and for understanding of long-term CV effects following charged particle radiotherapy.

Background: During the future exploration-type space missions, astronauts will be exposed to ionizing radiation (IR) for more than 1–2 years. The effect of cosmic IR during and after space flights on the cardiovascular (CV) system is unknown. Therefore, it is important to evaluate space IR effects on the CV system and determine potential post-mission degenerative excess relative risks (ERR) to the heart as a function of normal aging (IR + AGING model) as well as determine whether space IR may affect the processes of recovery after an adverse CV event (i.e. acute myocardial infarct, AMI) during normal aging (IR + AGING + AMI model). Methods: Nine-month-old C57BL6N male mice were IR once with proton (50 cGy, 1 GeV/n) or (56Fe 15 cGy, 1 GeV/n). IR-induced alterations in cardiac function were assessed by echocardiography (ECHO) and hemodynamic measurements (HEMO). AMI was induced by ligation of left anterior descending (LAD) coronary artery 10 months post-IR. Mice were monitored over 28 days post-AMI. Results: Compared with control, in the IR + AGING study group, left ventricular end-systolic pressure (LVESP) was significantly decreased in both 1H- and 56Fe-IR (P < 0.03, both), suggesting IR-associated decrease in contractile function 10 month post-IRs. However, compared with age-matched control mice (18 months), the LV end-diastolic pressure (LVEDP) was significantly increased (P < 0.05) and minimum LV pressure change (dP/dt min, mmHg/sec) was significantly decreased (P < 0.02) in 1H-IR but not 56Fe-IR mice, suggesting that a single 50 cGy full body 1H-IR decreases considerably the relaxation function of the heart 10 months post-AMI. Of note, an increase in LVEDP and a decrease in dP/dt min are indicators that heart is not pumping blood well and is an early independent prognostic CV risk factor for development of cardiac de-compensation. In all three IR + AGING + AMI study groups, in average, there was 10–15% mortality up to 3 days post-AMI surgery with ∼90% survival rate in all groups 28 days post-AMI. This is rather very good survival rate for 18- to 20-month-old mice after permanent LAD ligation. In the IR + AGING + AMI study group, the most harmful effects on myocardial recovery 10 months post-IR and 28 days post-AMI were observed in the 56Fe-IR group. LVESP was significantly decreased in 56Fe-IR vs control and 1H-IR mice (P < 0.04 and <0.02, respectively). LVEDP was 3-fold higher in 56Fe-IR vs 1H-IR mice (P < 0.004) but was only slightly higher (P = n.s.) compared with control mice. However, dP/dt max and dP/dt min were significantly decreased in 56Fe-IR vs control (P < 0.007 and <0.05, respectively) and 1H-IR mice (P < 0.0004 and <0.0015, respectively), suggesting that 56Fe-AMI hearts developed cardiac de-compensation. Summary: Our data in the IR + AGING study group strongly suggest that 10 months post-IR low-dose high-energy 1H-IR but not low-dose HZE (56Fe) particle IR affects considerably contractile and relaxation functions during normal aging. Conversely, our data in the IR + AGING + AMI study group at 10 months post-IR taken together with our previously reported data for AMI recovery 3 month after a single 50 cGy 1H-IR and 15 cGy 56Fe-IR indicate that 3 months and as long as 10 months after a single full-body IR, the 56Fe-IR is detrimental, whereas 1H-IR does not have negative effects on post-AMI recovery. In fact, single 1H-IR, at this dose, was considerably beneficial for post-AMI recovery at 3 months, as well as at 10 months post-IR. Major conclusions: Our longitudinal 1, 3 and 10 months studies in the IR + AGING and IR + AGING + AMI groups reveal that a single full-body low-dose 1H and HZE particle radiation (56Fe) have long-lasting negative effect on heart homeostasis during normal aging (predominantly 56Fe and at 10 months 1H-IR, as well), and present a significant CV risk for recovery after adverse CV event (exclusively 56Fe-IR, whereas 1H-IR at this dose could beneficial). Further, the divergent effects of low dose 1H-IR vs 56Fe-IR on heart function during normal aging vs after adverse CV event suggest significantly different biological responses responsible for this ion-dependent dichotomy over 10 months post-IR and necessitate further in-depth studies into underlying molecular mechanisms.