Differences in Cardiac Remodeling in Left-Sided Valvular Regurgitation: Implications for Optimal Definition of Significant Aortic Regurgitation.

BACKGROUND: Grading of aortic regurgitation (AR) and mitral regurgitation (MR) is similar in the cardiology guidelines despite distinct differences in left ventricular (LV) adaptive pathophysiology. OBJECTIVES: This study compared differences in LV remodeling in patients with similar degrees of AR and MR severity and evaluated optimal cutoffs for significant AR in relation to the outcome of aortic valve replacement or repair (AVR) during follow-up. METHODS: From 2008 to 2018, consecutive patients with isolated AR or MR who had cardiac magnetic resonance (CMR) were identified and CMR parameters were compared. Patients with left ventricular ejection fraction (LVEF) <50%, ischemic scar >5%, valve stenosis, or concomitant regurgitation were excluded. Patients were followed longitudinally for AVR. RESULTS: Baseline characteristics of isolated AR (n = 418) and isolated MR (n = 1,073) were comparable except for higher male proportion and hypertension in AR, while heart failure was more prevalent in MR. Indexed LV end-diastolic and end-systolic volumes and mass were higher in AR compared with MR at the same level of regurgitant fraction. During follow-up (mean 2.1 years), 18.7% of AR patients underwent AVR based on symptoms or LV remodeling. Interestingly, 38.0% of patients that underwent AVR within 3 months after CMR did not meet severe AVR by current guidelines of AR severity. AR regurgitant fraction>35% had high sensitivity (86%) and specificity (88%) for identifying patients who underwent AVR. CONCLUSIONS: For similar regurgitation severity, LV remodeling is different in AR compared with MR. Cardiac symptoms and significant LV remodeling in AR requiring AVR occur frequently in patients with less severity than currently proposed. The study findings suggest that the optimal threshold for severe AR with CMR is different than MR and is lower than currently stated in the guidelines.

Long term development of diastolic dysfunction and heart failure with preserved left ventricular ejection fraction in heart transplant recipients.

Heart transplant recipients (HTX) have several risk factors for heart failure which can trigger pro-inflammatory and fibrosis factors and set into motion pathophysiologic changes leading to diastolic dysfunction and HFpEF. The objective of the study was to determine if HTX recipients with dyspnea have diastolic dysfunction and HFpEF. Twenty-five HTX were included. LV systolic and diastolic functions were evaluated using conductance catheters to obtain pressure volume loops. LV function was assessed at rest and during moderate intensity exercise of the upper extremities. A significant increase occurred in LV minimal pressure (3.7 ± 3.3 to 6.5 ± 3.5 mmHg) and end diastolic pressure or EDP (11.5 ± 4 to 18 ± 3.8 mmHg, both P < 0.01) with exercise. With exercise, the time constant of LV relaxation shortened in 2, was unchanged in 3, and increased in the remaining patients (group results: rest 40 ± 11.6 vs 46 ± 9 ms, P < 0.01). LV chamber stiffness constant was abnormally increased in all but 2 patients. Indices of LV systolic properties were normal at rest but failed to augment with exercise. In 15 who agreed to blood draw, inflammation and fibrosis markers were obtained. A significant association was observed between LV EDP and Pro-Col III N-terminal (r = 0.58, P = 0.024) and IL-1-soluble receptor (r = 0.59, P = 0.02) levels. HTX have diastolic dysfunction and can develop HFpEF several years after cardiac transplantation. The abnormally increased LV chamber stiffness and the prolongation or lack of shortening of the time constant of LV relaxation with exercise are the underlying reasons behind the observed changes in LV diastolic pressures with exercise.

Rates, predictors, and outcomes of early readmissions after tricuspid valve surgery.

BACKGROUND: The data on readmissions following tricuspid valve repair/replacement (TVR) are scarce. We examined rates, predictors, causes, and outcomes of readmissions after TVR, using the National Readmission Database. METHODS: The International Classification of Diseases-9th version was used to identify the patients who underwent isolated TVR or concomitant aortic, mitral, and coronary bypass surgeries. Rates, causes, and outcomes were assessed using the analysis of variance and the χ2 test, and predictors of readmissions were evaluated using multivariate analysis. RESULTS: A total of 8254 patients who underwent TVR during 2013 to 2014 were included, of whom 1994 (24.16%) were isolated, and 6260 (75.84%) were performed concomitantly with other heart valve or coronary bypass surgery. A total of 1720 (20.84%) patients were readmitted within 30 days. The readmission rates were 448 (22.46%) after isolated TVR and similar after concomitant TVR (TVR + aortic valve replacement, TVR + mitral valve repair, TVR + coronary artery bypass graft, and TVR + multiple) (P = .194); whereas 1305 (20.11%) and 414 (23.45%) were after tricuspid valve repair and replacement (P = .080), respectively. The independent predictors of readmission were acute kidney injury during index visit and Charlson comorbidity index of more than 2. Mean time to readmission and median length of stay during readmission were 13.02 (±7.93) and 5 (interquartile range: 3-9) days, respectively. Total mortality during rehospitalization was 105 (6.1%), a very high (26.86%) number of patients were discharged to skilled facilities after readmission. CONCLUSIONS: One out of five patients were readmitted within 30 days after the TVR, associated with 6.1% mortality during rehospitalization, and very high need for skilled facility placement.

Validation of scoring system predicting permanent pacemaker implantation after transcatheter aortic valve replacement.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) is being increasingly performed in patients with severe aortic stenosis. Despite newer generation valves, atrioventricular (AV) conduction disturbance is a common complication, necessitating permanent pacemaker (PPM) implantation in about 10% of patients. Hence, it is imperative to improve periprocedural risk stratification to predict PPM implantation after TAVR. The objective of this study was to externally validate a novel risk-stratification model derived from the National Inpatient Sample (NIS) database that predicts risk of PPM from TAVR. METHODS: Components of the score included pre-TAVR left and right bundle branch block, sinus bradycardia, second-degree AV block, and transfemoral approach. The scoring system was applied to 917 patients undergoing TAVR at our institution from November 2011 to February 2017. We assessed its predictive accuracy by looking at two components: discrimination using the C-statistic and calibration using the Hosmer-Lemeshow goodness of fit test. RESULTS: Ninety patients (9.8%) required PPM. The scoring system showed good discrimination with C-statistic score of 0.6743 (95% CI: 0.618-0.729). Higher scores suggested increased PPM risk, that is, 7.3% with score ⩽3, 19.23% with score 4-6, and 37.50% with score ≥7. Patients requiring PPM were older (81.4 versus 78.7 years, P = .002). Length of stay and in-hospital mortality was significantly higher in PPM group. CONCLUSIONS: The NIS database derived PPM risk prediction model was successfully validated in our database with acceptable discriminative and gradation capacity. It is a simple but valuable tool for patient counseling pre-TAVR and in identifying high-risk patients.

Comparison of Echocardiographic Assessment of Tricuspid Regurgitation Against Cardiovascular Magnetic Resonance.

OBJECTIVES: The aim of this study was to compare echocardiographic methods of determining tricuspid regurgitation (TR) severity against TR regurgitant volume (TRRV) by cardiovascular magnetic resonance (CMR). BACKGROUND: TR is usually assessed using echocardiography, but it is not known how this compares with quantitative measurements of TR severity by CMR. METHODS: Echocardiographic and CMR methods were compared in 337 patients. Echocardiographic methods included jet size, hepatic vein flow, inferior vena cava diameter, percentage change in inferior vena cava diameter with inspiration, right atrial end-systolic area and volume, right ventricular end-diastolic and end-systolic areas and fractional area change, vena contracta diameter, effective regurgitant orifice area, and TRRV using the proximal isovelocity surface area method. TRRV by CMR was calculated as the difference between right ventricular end-diastolic and end-systolic volumes and systolic flow through the pulmonic valve. RESULTS: Echocardiographic parameters of TR severity had variable accuracy against TRRV by CMR (area under the curve range 0.58 for jet area/right atrial end-systolic area to 0.79 for hepatic vein flow). A multiparametric approach to assessing TR severity according to the 2017 American Society of Echocardiography criteria had 65% agreement with TR severity by CMR. A hierarchal approach based on signals with higher feasibility and accuracy against CMR had 68% agreement, without missing cases of severe TR by CMR. Agreement with CMR by the hierarchal approach was higher than that by the 2017 American Society of Echocardiography guidelines (p = 0.016). CONCLUSIONS: Several individual echocardiographic parameters of TR severity have satisfactory accuracy against TRRV by CMR. A multiparametric hierarchal approach resulted in 68% agreement with CMR and 100% agreement when a 1-grade difference in TR severity is considered acceptable.

Quantitative myocardial perfusion positron emission tomography and caffeine revisited with new insights on major adverse cardiovascular events and coronary flow capacity.

AIMS: To evaluate effects of caffeine on quantitative myocardial perfusion by positron emission tomography (PET) and associated major adverse cardiovascular events (MACE). METHODS AND RESULTS: Serum caffeine was measured for all 6087 PETs with 328 positive results (5.4%). Paired caffeine positive/negative PETs (84 patients for dipyridamole with median caffeine 1.6 mg/L, and additional 25 volunteers for regadenoson with median caffeine 7.4 mg/L) were compared for quantitative perfusion. Multivariate regression analysis for associations among caffeine, clinical/imaging variables, predicted caffeine probability was performed. MACEs were followed up to 9 years after PETs. For caffeine vs. no caffeine, respectively, stress flow was 1.74 ± 0.55 vs. 2.14 ± 0.53 for dipyridamole and 1.82 ± 0.61 vs. 2.33 ± 0.49 mL/min/g for regadenoson, and coronary flow reserve (CFR) was 2.26 ± 0.67 vs. 2.67 ± 0.72 for dipyridamole and 1.84 ± 0.33 vs. 2.31 ± 0.41 for regadenoson (all P < 0.001). Subjects were reclassified from high-risk CFR ≤2.0 with caffeine to low-risk CFR >2.0 without caffeine in 66.7% and 80% of dipyridamole and regadenoson caffeine-no-caffeine pairs, respectively. While relative images showed no differences, caffeine significantly altered coronary flow capacity (CFC) to false negative and false positive severity in 2.1% and 5.5% of the 328 caffeine positives, respectively (0.1% and 0.3% of 6087 PETs) but without change in severity guided management in most patients (92.4% of 328 caffeine or 99.6% of total 6087 PETs). CONCLUSION: Even low serum caffeine levels reduce quantitative perfusion during vasodilatory stress with false positive or false negative results minimized by empathic instruction, CFC analysis or repeat PET after strict caffeine abstention for definitive individualized risk stratification and management.

Outcomes of Acute Myocardial Infarction in Patients with Influenza and Other Viral Respiratory Infections.

BACKGROUND: Acute influenza infection can trigger acute myocardial infarction, however, outcome of patients with acute myocardial infarction during influenza infection is largely unknown. METHODS: Patients ≥18 years old with ST-elevation and non-ST-elevation myocardial infarction during January 2013-December 2014 were identified using the National Inpatient Sample. The clinical outcomes were compared among patients who had no respiratory infection to the ones with influenza and other viral respiratory infections using propensity score-matched analysis. RESULTS: Of 1,884,985 admissions for acute myocardial infarction, acute influenza and other viral infections were diagnosed in 9,885 and 11,485 patients, respectively, accounting for 1.1% of patients. Acute myocardial infarction patients with concomitant influenza infection had a worse outcome than those with acute myocardial infarction alone, in terms of in-hospital case fatality rate, development of shock, acute respiratory failure, acute kidney injury, and higher rate of blood transfusion after propensity scores. The length of stay is also significantly longer in influenza patients with acute myocardial infarction, compared with patients with acute myocardial infarction alone. However, patients who developed acute myocardial infarction during other viral respiratory infection have a higher rate of acute respiratory failure but overall lower mortality rate, and are less likely to develop shock or require blood transfusion after propensity match. Despite presenting with acute myocardial infarction, less than one-fourth of patients with concomitant influenza infection underwent coronary angiography, but more than half (51.4%) required revascularization. CONCLUSION: Influenza infection is associated with worse outcomes in acute myocardial infarction patients, and patients were less likely to receive further evaluation with invasive coronary angiography.

National 10-year trends and outcomes of isolated and concomitant tricuspid valve surgery.

BACKGROUND: The data on the trends and comparative outcomes after isolated and concomitant tricuspid valve repair/replacement (TVR) is scarce. METHODS: The International Classification of Diseases - 9th version was used to identify the patients who underwent TVR, using the National Inpatient Sample. Outcomes were evaluated using the analysis of variance and Chi-square test, and trends across the years were tested via Cochran-Armitage Test. RESULTS: Of 6868 patients who underwent TVR between 2005-14, 1601 (23%) were isolated. Over the 10-years period, the number of total and isolated TVR has steadily increased (P<0.001). The proportion of patients undergoing repair has increased compared to replacement. Overall in-hospital mortality was 8.5% and 7.7% (p=0.28), permanent pacemaker requirement was 11.24% and 10.69% (P=0.53), blood transfusion rates were 32.6% and 37.9% (P<0.001), and the post-procedure length of stay (LOS) was 14.1±0.44 and 12.5±0.17 days (P<0.001) after isolated and concomitant TVR respectively. High (26.25%) number of patients were discharged to skilled facility. The operative mortality associated with TV repair was lower than with replacement (6.8% versus 11.15%, P<0.001), but the mortality trend over the 10-years has stayed relatively stable. Independent predictors of mortality were age >50 years, heart failure, cerebrovascular accident, end-stage renal disease, peripheral vascular disease, liver disease, and TV replacement. CONCLUSIONS: Both isolated and concomitant TVR has increased over the last 10 years, however is associated with high mortality, complications, need for skilled facility placement, and longer LOS. The mortality after TV replacement was significantly higher than that after repair.

Stress-Induced Cardiomyopathy in Cancer Patients.

Takotsubo syndrome, also known as stress-induced cardiomyopathy (SC), is underrecognized in cancer patients. This study aims to investigate the incidence, natural history, and triggers of SC in cancer patients and its impact on cancer therapy and overall survival. A total of 30 subjects fulfilled the diagnostic criteria for SC at MD Anderson Cancer Center over a 6-year period. Clinical presentation, electrocardiogram, laboratory data, and transthoracic echocardiogram results registered during the acute phase and follow-up were collected. All patients underwent coronary angiography. The most frequent presenting symptoms were chest pain in 63.3% of the patients and shortness of breath/dyspnea on exertion in 27% of the patients. T-wave inversion was a more common electrocardiographic presentation (60%) than ST elevation (13.3%). The median and interquartile range of peak creatine kinase MB fraction, troponin I, and brain natriuretic peptide were creatine kinase MB fraction 8.9, 4.6 to 21.1; troponin I 1.31, 0.7 to 3.3; and brain natriuretic peptide 1,124, 453.5 to 2,369.5. The most common complication of SC was cardiogenic shock requiring inotropic agents (20%). Of the 21 patients who required ongoing cancer treatment, 16 were able to resume chemotherapy, 5 underwent surgery, and 4 received radiation treatment. Median time to resume cancer treatment was 20 days after SC. None of the patients experienced recurrence of SC and other cardiac events. In conclusion, SC should be considered in the differential diagnosis of cancer patients who present with chest pain and ECG findings characteristic of acute coronary syndrome. Most of these patients normalize ejection fraction and may resume cancer therapy early.

Early readmissions after transcatheter and surgical aortic valve replacement.

OBJECTIVES: We aimed to determine and compare the prevalence, and predictors of readmissions after the transcatheter aortic valve replacement (TAVR) and surgical aortic valve replacement (SAVR). BACKGROUND: There are limited data on the readmission rates after TAVR in comparison with SAVR. METHODS: We analyzed the data from 2013 National Readmission Database. Propensity-matched pairs were used to analyze differences in readmission rates between TAVR and SAVR for patients aged ≥65. RESULTS: A total of 24,020 (TAVR-transfemoral 3,469, TAVR-transapical 1,433, SAVR 19,118) patients were included. The readmission rates were not statistically different for all propensity-matched TAVR and SAVR patients (17.2% vs. 20.6%, P = 0.28). However, in subgroup analysis, transapical TAVR had the highest readmission rate (22.8% vs. 16.5% vs. 16.0%, P < 0.001, respectively) and readmission leading to death (7.1% vs. 5.3% vs. 3.9%, P = 0.022, respectively) when compared with transfemoral TAVR and SAVR. In all the groups, two-thirds of readmissions were due to noncardiac causes. Congestive heart failure (CHF) and arrhythmia were the most frequent cardiac etiologies. The independent predictors of readmission were female sex, CHF, and chronic obstructive pulmonary disease. Patients who received care in teaching hospitals had lower probability of readmission. CONCLUSIONS: One of six patients were readmitted within 30 days after the aortic valve replacement. On propensity score analysis, there were no significant differences between the early readmission rates between TAVR and SAVR groups. However, the patients undergoing transapical TAVR were at higher risk for readmission, and subsequent deaths when compared with transfemoral TAVR and SAVR. © 2017 Wiley Periodicals, Inc.

Clinical Utility of Enhanced Relative Activity Recovery on Systolic Myocardial Perfusion SPECT: Lessons from PET.

UNLABELLED: SPECT and PET myocardial perfusion images show greater myocardial intensity and homogeneity in systole than diastole because of greater systolic myocardial thickness, less partial volume loss, and enhanced activity recovery. Consequently, conventional myocardial perfusion images obtained from whole cardiac cycles have lower myocardial intensity and greater heterogeneity than systolic images. Considering relative activity distribution on SPECT systolic images may add clinical utility to whole-cycle images and wall motion. METHODS: Patients undergoing coronary angiogram within 4 mo after SPECT myocardial perfusion imaging were reviewed. Images were interpreted by 2 masked interpreters using a 17-segment, 5-point scale to determine summed rest scores (SSS), summed stress scores, and summed difference scores on conventional and systolic images in 603 patients (55.6% no coronary artery disease [no-CAD] and 44.4% CAD). Studies were considered normal when the SSS was less than 4 and summed difference score was less than 2. RESULTS: In the no-CAD group, systolic SSS was lower than SSS from conventional images (2 ± 2.3 vs. 3 ± 2.6, P < 0.001). In contrast, SSS derived from systolic and conventional images were not different in the obstructive CAD group (9.1 ± 7.6 vs. 9.2 ± 7.4, P = 0.559). When systolic images were considered, true-negative studies increased from 27.2% to 43.3% (P < 0.001) whereas false-positive studies decreased from 28.4% to 12.3% (P < 0.001). True-positive (38% vs. 37.2%, P = 0.505) and false-negative studies (6.5% vs. 7%, P = 0.450) were not significantly changed. Diagnostic accuracy increased from 65.2% to 80.8% (P < 0.001). CONCLUSION: For gated SPECT myocardial perfusion imaging, when relative activity distribution on systolic images was considered, false-positive studies were reduced and diagnostic accuracy was improved.

Epstein-barr virus-related hemophagocytic lymphohistiocytosis: hematologic emergency in the critical care setting.

Hemophagocytic lymphohistiocytosis (HLH) is a rare and potential life-threatening clinical syndrome that results from uncontrolled activation of the immune system. Secondary HLH, more commonly observed in adult patients, is seen in the context of underlying triggering conditions. Epstein-Barr virus (EBV) has been recognized as the leading infectious cause and is associated with a poor outcome. As clinical and laboratory features of HLH could overlap with septic shock syndrome in most patients, the diagnosis of HLH, especially in adults, is the most challenging aspect of the disease that results in delayed recognition and treatment of rapidly progressive multiorgan system failure. We report a case of Hemophagocytic lymphohistiocytosis in a patient who presented with signs of septic shock syndrome and we review the literature on the topic.

Prevention of anthracycline-induced cardiotoxicity: challenges and opportunities.

Anthracycline compounds are major culprits in chemotherapy-induced cardiotoxicity, which is the chief limiting factor in delivering optimal chemotherapy to cancer patients. Although extensive efforts have been devoted to identifying strategies to prevent anthracycline-induced cardiotoxicity, there is little consensus regarding the best approach. Recent advances in basic mechanisms of anthracycline-induced cardiotoxicity provided a unified theory to explain the old reactive-oxygen species hypothesis and identified topoisomerase 2ß as the primary molecular target for cardioprotection. This review outlines current strategies for primary and secondary prevention of anthracycline-induced cardiotoxicity resulting from newly recognized molecular mechanisms and identifies knowledge gaps requiring further investigation.

Emerging paradigms in cardiomyopathies associated with cancer therapies.

The cardiovascular care of cancer patients (cardio-oncology) has emerged as a new discipline in clinical medicine, given recent advances in cancer therapy, and is driven by the cardiovascular complications that occur as a direct result of cancer therapy. Traditional therapies such as anthracyclines and radiation have been recognized for years to have cardiovascular complications. Less expected were the cardiovascular effects of targeted cancer therapies, which were initially thought to be specific to cancer cells and would spare any adverse effects on the heart. Cancers are typically driven by mutations, translocations, or overexpression of protein kinases. The majority of these mutated kinases are tyrosine kinases, though serine/threonine kinases also play key roles in some malignancies. Several agents were developed to target these kinases, but many more are in development. Major successes have been largely restricted to agents targeting human epidermal growth factor receptor-2 (mutated or overexpressed in breast cancer), BCR-ABL (chronic myelogenous leukemia and some cases of acute lymphoblastic leukemia), and c-Kit (gastrointestinal stromal tumor). Other agents targeting more complex malignancies, such as advanced solid tumors, have had successes, but have not extended life to the degree seen with chronic myelogenous leukemia. Years before the first targeted therapy, Judah Folkman correctly proposed that to address solid tumors one had to target the inherent neoangiogenesis. Unfortunately, emerging evidence confirms that angiogenesis inhibitors cause cardiac complications, including hypertension, thrombosis, and heart failure. And therein lies the catch-22. Nevertheless, cardio-oncology has the potential to be transformative as the human cardiomyopathies that arise from targeted therapies can provide insights into the normal function of the heart.