Impact of controlled hypothermic preservation on outcomes following heart transplantation.

BACKGROUND: Severe primary graft dysfunction (PGD) is a major cause of early mortality after heart transplant, but the impact of donor organ preservation conditions on severity of PGD and survival has not been well characterized. METHODS: Data from US adult heart-transplant recipients in the Global Utilization and Registry Database for Improved Heart Preservation-Heart Registry (NCT04141605) were analyzed to quantify PGD severity, mortality, and associated risk factors. The independent contributions of organ preservation method (traditional ice storage vs controlled hypothermic preservation) and ischemic time were analyzed using propensity matching and logistic regression. RESULTS: Among 1,061 US adult heart transplants performed between October 2015 and December 2022, controlled hypothermic preservation was associated with a significant reduction in the incidence of severe PGD compared to ice (6.6% [37/559] vs 10.4% [47/452], p = 0.039). Following propensity matching, severe PGD was reduced by 50% (6.0% [17/281] vs 12.1% [34/281], respectively; p = 0.018). The Kaplan-Meier terminal probability of 1-year mortality was 4.2% for recipients without PGD, 7.2% for mild or moderate PGD, and 32.1%, for severe PGD (p < 0.001). The probability of severe PGD increased for both cohorts with longer ischemic time, but donor hearts stored on ice were more likely to develop severe PGD at all ischemic times compared to controlled hypothermic preservation. CONCLUSIONS: Severe PGD is the deadliest complication of heart transplantation and is associated with a 7.8-fold increase in probability of 1-year mortality. Controlled hypothermic preservation significantly attenuates the risk of severe PGD and is a simple yet highly effective tool for mitigating post-transplant morbidity.

Heart transplantation from COVID-positive donors with 6-month follow-up: A case series.

BACKGROUND: Data on long term outcomes in heart transplant recipients from Coronavirus disease 2019 (COVID-19) positive donors are limited. METHODS AND RESULTS: We present a series of nine patients who underwent heart transplants from COVID-19 PCR-positive donors between November 2021 to August 2022 with mean follow-up of 12.12 ± 3 months. All the recipients received two doses of COVID-19 vaccine and had at least 6 months follow-up. Eight recipients had acceptable long-term outcomes; one patient died during index admission from primary graft dysfunction. Details regarding donor and recipient characteristics, management and outcomes are provided. Two patients developed deep vein thrombosis, and one patient underwent pacemaker implantation for sinus node dysfunction. Among the surviving eight patients, none developed COVID-19 infection during follow-up period. There was no significant difference in outcome parameters when compared to patients who received hearts from donors who tested negative for COVID-19 during the same time period at our center. CONCLUSION: Keeping in mind the significant waitlist mortality in patients awaiting heart transplantation, COVID-19-positive donors should be considered for heart transplantation to help expand the donor pool and potentially reduce waitlist mortality.

Donor Age, Sex, and Cause of Death and Their Relationship to Heart Transplant Recipient Cardiac Death.

BACKGROUND: Recent studies indicate that donor innate immune responses participate in initiating and accelerating innate responses and allorecognition in the recipient. These immune responses negatively affect recipient outcomes and predispose recipients to cardiovascular death (CV death). We hypothesized that a donor cause of death (COD) associated with higher levels of innate immune response would predispose recipients to more adverse outcomes post-transplant, including CV death. METHODS: We performed a single-institution retrospective analysis comparing donor characteristics and COD to recipient adverse cardiovascular outcomes. We analyzed the medical records of local adult donors (age 18-64) in a database of donors where adequate data was available. Donor age was available on 706 donors; donor sex was available on 730 donors. We linked donor characteristics (age and sex) and COD to recipient CV death. The data were analyzed using logistic regression, the log-rank test of differences, and Tukey contrast. RESULTS: Donor age, female sex, and COD of intracranial hemorrhage were significantly associated with a higher incidence of recipient CV death. CONCLUSIONS: In this single institution study, we found that recipients with hearts from donors over 40 years, donors who were female, or donors who died with a COD of intracranial hemorrhage had a higher frequency of CV death. Donor monitoring and potential treatment of innate immune activation may decrease subsequent recipient innate responses and allorecognition stimulated by donor-derived inflammatory signaling, which leads to adverse outcomes.

Transcatheter aortic valve replacement for aortic insufficiency in a patient with aortic root Thrombus and left ventricular assist device: A risk worth taking?

A 61-year-old man with end-stage ischemic cardiomyopathy post HeartMate 3 (Abbott laboratories, Chicago, Illinois, USA) left ventricular assist device (LVAD) implant was hospitalized after he had recurrent ventricular tachycardia requiring implantable cardioverter-defibrillator shocks. His transthoracic echocardiogram and computed tomography angiography of the chest showed presence of trace aortic insufficiency (AI) and aortic root thrombus (ART) of non-coronary cusp without obstruction of right or left coronary artery ostium despite therapeutic international normalized ratio. He presented again 3 months later with worsening heart failure signs and symptoms. Transesophageal echocardiogram showed progression to severe AI and persistent ART. Despite hemodynamically guided LVAD speed optimization, inotropic support, and diuresis, the patient continued to deteriorate with worsening renal function. The patient was not a transplant candidate due to frailty. After multi-disciplinary discussion he underwent successful 29-Sapien S3 (Edwards Lifesciences, Irvine, CA, USA) transcatheter aortic valve replacement utilizing distal protection filters in bilateral internal carotid arteries for stroke prevention. This case provides novel insight to physicians treating LVAD patients regarding management of severe AI in the setting of ART. Learning objective: We report a rare approach employed for management of aortic insufficiency (AI) in a patient who also had an aortic root thrombus and left ventricular assist device (LVAD) that traditionally requires cardiac transplantation. Our patient had a favorable outcome with a minimally invasive transcatheter aortic valve replacement. With this case, we hope to generate awareness amongst physicians treating patients about management alternatives and approach of a commonly encountered, life-threatening complication of AI in patients with LVAD.

Cytomegalovirus infection in heart transplant patient presenting as appendicitis.

Cytomegalovirus (CMV) may manifest in various ways. While immunocompetent hosts may be asymptomatic or present with a mononucleosis-like illness, immunocompromised patients can have organ-specific disease capable of significant morbidity and mortality. CMV appendicitis is a particularly rare presentation. A 22-year-old female with a history of orthotopic heart transplantation presented to our hospital with a three-day history of worsening abdominal pain. A computed tomography scan of her abdomen was consistent with acute uncomplicated appendicitis, and she underwent laparoscopic appendectomy. Pathology revealed acute appendicitis with numerous large cells with intranuclear "owl's eye" inclusions characteristic of CMV. Her CMV viral load was elevated at 327,018 IU/ml. She was started on ganciclovir which resulted in improvement of her CMV level to 30,118 IU/ml within three weeks. CMV is a frequent cause of opportunistic infection in solid organ transplant patients and commonly involves the gastrointestinal tract. Acute appendicitis is a rarely reported complication to consider in the differential diagnosis of abdominal pain in immunocompromised patients. Learning objective: Heart transplant recipients are at increased risk for opportunistic infections. Cytomegalovirus (CMV) is a frequent culprit and can present with a broad range of disease. A particularly rare presentation is that of acute appendicitis. We describe a case of a young woman with CMV appendicitis following orthotopic heart transplant.

Trends and Outcomes of Cardiogenic Shock in Patients With End-Stage Renal Disease: Insights From USRDS Database.

BACKGROUND: There is a paucity of data regarding epidemiology, temporal trends, and outcomes of patients with cardiogenic shock (CS) and end-stage renal disease (chronic kidney disease stage V on hemodialysis). METHODS: This is a retrospective cohort study using the United States Renal Data System database from January 1, 2006 to December 31, 2019. We analyzed trends of CS, percutaneous mechanical support (intraaortic balloon pump, percutaneous ventricular assist device [Impella and Tandemheart], and extracorporeal membrane oxygenation) utilization, index mortality, 30-day mortality, and 1-year all-cause mortality in end-stage renal disease patients. RESULTS: A total of 43 825 end-stage renal disease patients were hospitalized with CS (median age, 67.8 years [IQR, 59.4-75.8] and 59.1% men). From 2006 to 2019, the incidence of CS increased from 275 to 578 per 100 000 patients (Ptrend<0.001). The index mortality rate declined from 54.1% in 2006 to 40.8% in 2019 (Ptrend=0.44), and the 1-year all-cause mortality decreased from 63% in 2006 to 61.8% in 2018 (Ptrend=0.73), but neither trend was statistically significant. There was a significantly decreased utilization of intra-aortic balloon pumps from 17 832 to 7992 (Ptrend<0.001), increased utilization of percutaneous ventricular assist device from 137 to 5201 (Ptrend<0.001) and increase in extracorporeal membrane oxygenation use from 69 to 904 per 100 000 patients (Ptrend<0.001). After adjusting for covariates, there was no significant difference in index mortality between CS patients requiring percutaneous mechanical support versus those not requiring percutaneous mechanical support (odds ratio, 0.97 [CI, 0.91-1.02]; P=0.22). On multivariable regression analysis, older age, peripheral vascular disease, diabetes, and time on dialysis were independent predictors of higher index mortality. CONCLUSIONS: The incidence of CS in end-stage renal disease patients has doubled without significant change in the trend of index mortality despite the use of percutaneous mechanical support.

Endomyocardial biopsy-proven hydroxychloroquine-induced cardiomyopathy in a patient with rheumatoid arthritis.

Hydroxychloroquine is a disease-modifying antirheumatic drug used for various rheumatological conditions. Its long-term use is well-known to have toxic effects on cardiac muscle cells. We present a biopsy-proven case of hydroxychloroquine-induced cardiotoxicity with detailed histopathological and imaging findings. The patient was referred to our heart failure clinic for concerns of reduction in left ventricular ejection fraction despite being on guideline-directed medical therapy. She had been diagnosed with rheumatoid arthritis, pulmonary hypertension and then subsequently heart failure with reduced ejection fraction 5 years ago. The evaluation included right heart catheterisation, cardiac MRI and endomyocardial biopsy. Light and electron microscopy showed myocyte hypertrophy and vacuolar change, abnormal mitochondria, myeloid bodies and curvilinear bodies. These findings were specific for hydroxychloroquine-induced cardiomyopathy. This case highlights the importance of clinical monitoring, early suspicion and consideration of drug-induced toxicities as a culprit for heart failure.

Impact of Biopsy Proven Liver Fibrosis on Patients Undergoing Evaluation and Treatment for Advanced Heart Failure Surgical Therapies.

There is a paucity of data regarding the impact of liver fibrosis on patients with stage D heart failure (HF). We conducted a retrospective study (January 1, 2017 to December 12, 2020) in patients with stage D HF who underwent liver biopsy as part of their advanced HF therapy evaluation. Baseline characteristics and 1-year outcomes were compared between no- or mild-to-moderate-fibrosis (grade 0 to 2) and advanced-fibrosis (grade 3 to 4) groups. Of 519 patients with stage D HF, 136 who underwent liver biopsy (113 [83%] no or mild-to-moderate fibrosis and 23 [17%] advanced fibrosis) were included. A total of 71 patients (52%) received advanced HF therapies (23 heart transplantation, 48 left ventricular assist devices). One-year mortality was higher among patients with advanced fibrosis (52% vs 18%, p <0.001). Further subgroup analysis suggested a trend toward increased 1-year mortality among patients with advanced fibrosis who underwent advanced therapies (37% vs 13%, p = 0.09). There was a trend of lower likelihood of receiving advanced HF therapies in the advanced-fibrosis group, only 1 heart transplantation and 7 left ventricular assist devices, but it did not reach statistical significance (35% vs 56%, p = 0.06). After adjustment for confounders, degree of liver fibrosis was an independent predictor of mortality (odds ratio 6.2; 95% 1.27 to 30.29, p = 0.02). We conclude that advanced liver fibrosis is common among patients with stage D HF who undergo evaluation for advanced HF surgical therapies and significantly increases 1-year mortality. Further larger studies are needed to support our findings.

Loperamide-induced cardiogenic syncope: a case report of a life-threatening presentation of an over-the-counter drug.

Background: Loperamide at supratherapeutic doses can cause cardiac toxicity, presenting as cardiogenic shock, prolonged QT, malignant arrhythmias, or in severe cases sudden cardiac death. Surreptitious loperamide use is difficult to diagnose. We present an interesting case of loperamide use presenting with polymorphic ventricular tachycardia, cardiogenic shock. Case summary: A 25-year-old female presented with multiple syncopal episodes for 12 months with an electrocardiogram showing a Brugada-like pattern for which she underwent implantable cardioverter-defibrillator placement. One day following the procedure, she developed cardiogenic shock and was transferred to our tertiary care centre. Extensive workup was unrevealing. She responded well to supportive management, recovering from shock and was transferred to the floor. Unfortunately, she again developed cardiogenic shock, ultimately leading to cardiac arrest. Given the unclear cause for her cardiovascular symptoms, futher medication history was obtained. It was revealed that she was taking 100-150 tablets of loperamide per day. The decision was made to treat with intralipid emulsion therapy empirically given the strong suspicion for loperamide toxicity. The patient recovered well with supportive care. Loperamide levels returned elevated at 190 ng/mL. Repeated studies showed improvement of the conduction block, resolution of arrhythmias, and recovery of right and left ventricular function. Discussion: Acute loperamide toxicity can present as biventricular failure, with difficult-to-control arrhythmias. It requires a high index of suspicion. Treatment for loperamide toxicity is mainly supportive, lipid emulsion therapy can be considered in severe or refractory cases.

Rare case of chronic Q fever myocarditis in end stage heart failure patient: A case report.

BACKGROUND: Q fever myocarditis is a rare disease manifestation of Q fever infection caused by Coxiella burnetii. It is associated with significant morbidity and mortality if left untreated. Prior studies have reported myocarditis in patients with acute Q fever. We present the first case of chronic myocarditis in an end-stage heart failure patient with chronic Q fever infection. CASE SUMMARY: A 69-year-old male was admitted with dyspnea on exertion, hypotension and bilateral lower extremity edema for a few months. He has a past medical history of ischemic cardiomyopathy with left ventricular ejection fraction of 25%, implantable cardioverter defibrillator in place, bioprosthetic aortic valve and mitral valve replacement. He continued to have shortness of breath despite diuresis along with low grade fevers. Initial infectious work up came back negative. On further questioning, the patient was found to have close contact with farm animals and the recurrent fevers prompted the work-up for Q fever. Q fever serologies and cardiac positron emission tomography confirmed the diagnosis of chronic Q fever myocarditis. He was then successfully treated with doxycycline and hydroxychloroquine for 18 mo. CONCLUSION: Chronic Q fever myocarditis, if left untreated, carries a poor prognosis. It should be kept in differentials, especially in patients with recurrent fevers and contact with farm animals.

Outcomes in Patients With Chronic Kidney Disease and End-stage Renal Disease and Durable Left Ventricular Assist Device: Insights From the United States Renal Data System Database.

BACKGROUND: There is paucity of data regarding durable left ventricular assist device (LVAD) outcomes in patients with chronic kidney disease (CKD) stages 3-5 and CKD stage 5 on dialysis (end-stage renal disease [ESRD]). METHODS AND RESULTS: We conducted a retrospective study of Medicare beneficiaries with ESRD and a 5% sample of patients with CKD with an LVAD (2006-2018) to determine 1-year outcomes using the United States Renal Data System database. The LVAD implantation, comorbidities, and outcomes were identified using appropriate International Classification of Diseases, 9th and 10th edition codes. We identified 496 patients with CKD and 95 patients with ESRD who underwent LVAD implantation. The patients with ESRD were younger (59 years vs 66 years; P < .001), had more Blacks (40% vs 24.6%, P = .009), compared with the CKD group. The 1-year mortality (49.5% vs 30.9%, P < .001) and index mortality (27.4% vs 16.7%, P = .014) rates were higher for patients with ESRD. A subgroup analysis showed significantly higher mortality in ESRD vs CKD 3 (49.5% vs 30.2%, adjusted P = .009), but no significant difference in mortality between stage 3 vs 4/5 (30.2% vs 30.8%, adjusted P = .941). There was no significant difference in secondary outcomes (bleeding, stroke, and sepsis/infection) during follow-up between the 2 groups. CONCLUSIONS: Patients with ESRD undergoing LVAD implantation had significantly higher index and 1-year mortality rates compared with patients with CKD.

Early and aggressive presentation of wild-type transthyretin amyloid cardiomyopathy: A case report.

BACKGROUND: Wild-type transthyretin amyloidosis (ATTRwt) is the most common form of transthyretin amyloid cardiomyopathy, occurring mostly over age of 60 years (mean age of 80 years). Mean survival without treatment is 3.6 years, making early detection imperative. We report an unusual case of a 58-year-old patient with ATTRwt cardiomyopathy requiring heart transplantation. CASE SUMMARY: A 58-year-old male presented with progressive fatigue, shortness of breath, weight gain, leg swelling, orthopnoea, and paroxysmal nocturnal dyspnoea for several months. Approximately ten months before this clinical presentation, the patient had first received a diagnosis of heart failure with reduced ejection fraction (EF) of 15% to 20%. The patient was started on appropriate guideline-directed medical therapy with only mild improvement in his EF. Upon further investigation, echocardiogram, technetium pyrophosphate scan (Tc PYP), and cardiac magnetic resonance imaging (cMRI) suggested a diagnosis of amyloidosis, and ATTRwt was subsequently confirmed with native heart tissue biopsy, congo red staining, liquid chromatography-tandem mass spectrometry, and genetic testing. The patient was successfully treated with heart transplantation and is doing well post-transplant. CONCLUSION: Wild-type ATTR amyloidosis should be kept on differentials in all patients (even less than 60 years old) with non-ischemic cardiomyopathy, especially in the setting of increased ventricular wall thickness and other classic echocardiogram, cMRI, and Tc PYP findings. Early diagnosis and management can be consequential in improving patient outcomes.

Thirty-day readmissions among patients with cardiogenic shock who underwent extracorporeal membrane oxygenation support in the United States: Insights from the nationwide readmissions database.

Background: There is a paucity of data on readmission rates and predictors of readmissions in cardiogenic shock patients after contemporary Extracorporeal Membrane Oxygenation (ECMO) use. Methods: Using the Nationwide Readmission Database, we included adult patients (≥18 years old) hospitalized between January to November 2016-2018 for cardiogenic shock requiring ECMO support. Thirty-day readmission rates, associated variables, and predictors of readmission were assessed. Results: A total of 10,723 patients underwent ECMO for cardiogenic shock. After excluding patients who died (n = 5602; 52%) and who underwent LVAD or OHT during index admission (n = 892; 8%), 4229 patients discharged alive were included. Of those, 694 (16.4%) were readmitted within 30 days. The median time to readmission was 10 days. Diabetes mellitus (OR = 1.77; 95% CI 1.32-2.37), chronic liver disease (OR = 1.35; 95% CI 1.03-1.77), and prolonged LOS (≥30 days; OR = 1.38; 95% CI 1.05-1.81) were associated with increased risk of 30-day readmissions while heart failure diagnosis (OR = 0.69; 95% CI 0.50-0.95) and short-term hospital post-discharge care (OR = 0.53; 95% CI 0.28-0.99) conferred a lower risk. Sepsis, followed by congestive heart failure, was the most common readmission diagnoses. Conclusions: Patients with CS requiring ECMO support have high mortality and high 30-day readmission rates, with sepsis being the leading cause of readmissions followed by heart failure.

Does a brief functional assessment in the emergency department predict outcomes of patients admitted with heart failure? The FASTER-HF study.

BACKGROUND: Evaluation of patients with acute decompensated heart failure includes symptom review, biomarker measurement and comorbidity assessment. Early objective evaluation of functional status is generally not performed. AIM: To investigate whether a simple low-impact functional assessment and measurement of sarcopenia would be safe, feasible and predictive of hospital length of stay and all-cause 30-day hospital readmission. METHODS: We administered 3-minute bicycle ergometry and hand grip strength tests at admission and discharge to patients for whom a decision to admit for heart failure management was made in the emergency department. Associations were examined between test results and length of stay and 30-day readmission. Exclusion criteria included acute coronary syndrome, hypoxia, end-stage renal disease, dementia/delirium and inability to sit at bedside. The Kansas City Cardiomyopathy Questionnaire-12, the Patient Health Questionnaire-2 and the visual analogue scale for dyspnoea were administered at admission, the visual analogue scale at discharge and the Kansas City Cardiomyopathy Questionnaire-12 at 30 days. RESULTS: Fifty patients were enrolled: 58% were female; the mean age was 66.2±12.5 years; 24% had heart failure with preserved ejection fraction. Bicycle ergometry variables did not correlate with outcomes. Change in handgrip strength correlated with readmission, but not after adjustment (rpartial=0.14; P=0.35). Total diuretic dose correlated with length of stay; only discharge visual analogue scale and baseline lung disease had significant adjusted correlations with readmission. CONCLUSIONS: Functional assessment in the emergency department of patients admitted for heart failure did not predict outcomes. However, the prognostic value of these assessments for decision-making about disposition (admission or discharge) may still be warranted.

Vasopressin antagonism for decompensated right-sided heart failure.

BACKGROUND: Targeted treatment for decompensated right heart failure (RHF) with or without left heart failure is lacking. Vasopressin antagonists (vaptans) may offer an option by increasing urine output and fluid mobilization when used in acute decompensated RHF without impacting blood pressure or renal function, both common complications of loop diuretics. METHODS AND RESULTS: We searched electronic medical records from 2 institutions over 4 years for patients with RHF treated with vaptans. Urine output, creatinine, BUN and sodium, 1 day pre- versus 1 day post-vaptan initiation were compared. Baseline (admission) pre-vaptan values for patients with RHF who met inclusion criteria (n = 112) were RAP, median (interquartile range) = 19 (13-24) mmHg; cardiac index, mean ±â€¯standard deviation = 1.8 ±â€¯0.4 L/min/m2; BNP, 1078 (523-1690) pg/ml; creatinine clearance of 51 (39-69) ml/min, BUN, 37 (26-54) mg/dl, and serum [Na+] 132 (126-135) mEq/L. Most patients (n = 103/112) received intravenous inotrope (prior to vaptan, n = 91). Overall length of stay was 27 (16-43) days. Vaptan treatment (90% tolvaptan, 10% conivaptan) was associated with increased 24 h urine output, 1517 (906-2394) vs 2337 (1425-3744) mL, p = 0.005, and [Na+], 127 (124-130) vs 130 (126-135) mEq/L, p = 0.001, without significant change in Cr or BUN. Furosemide IV dose equivalent decreased or remained unchanged in 75% of patients at 24 h and 64% at 72 h compared to the 24 h prior to vaptan use. CONCLUSION: Vaptans were associated with a significant increase in urine output and serum sodium with an apparent reduction or stabilization of furosemide equivalent dosing in the early treatment period in patients with decompensated RHF. Vaptans may offer a management option for patients failing conventional diuretic-based treatment.

Subgroup analyses of randomized clinical trials in heart failure: facts and numbers.

Subgroup analyses of major randomized clinical trials in heart failure are published frequently, but their impact on medical knowledge and practice guidelines has not been previously reported. In a novel analysis, we determined number of citations, impact factors, number of authors, and citations in guidelines of both parent trials and sub-studies; we also qualitatively assessed whether the analyses were described as post-hoc and non-pre-specified. A total of 229 sub-studies evaluating outcomes in patient subgroups were published (median 6, range 0-36 per trial). The number of subjects in the parent trials positively correlated with number of sub-studies (rho = 0.51, P = 0.009). The subgroups are frequently not pre-specified. The impact factors of sub-studies were lower in comparison to the parent trials as were the number of citations two years after the publication date; in addition, parent trials were cited more frequently in European and American professional guidelines compared with the sub-studies. We maintain that the sub-studies derived from major heart failure trials are frequently published, but their contribution to clinical guidelines and medical knowledge are highly debatable.